Current research activities

• Division Research
• Ari D. Brooks, MD
• Julia C. Tchou, MD, PhD
• Jennifer Q. Zhang, MD

Najjia N. Mahmoud, MD

The Division of Colon and Rectal Surgery is committed to ongoing efforts to improve perioperative care and long-term outcomes in the surgical treatment of colorectal disease through clinical trials and retrospective studies.  Dr. Mahmoud’s research group is comprised of a surgical postdoctoral fellow, surgical residents, medical students, and other technical staff.

Ongoing research projects:

1. A Randomized Double-Blind Study of 2% Chlorhexidine Gluconate / 70% Isopropyl Alcohol vs 10% Povidone-Iodine Paint for Perioperative Skin Preparation in Open Elective Colorectal Surgery.
2. A prospective study comparing the efficacy of two FDA approved preoperative skin antiseptics in the prevention of superficial surgical site infection in colorectal surgery.
3. Colorectal Surgical Site Infection a  Retrospective Study
4. A Retrospective Study of Thromboembolic Events in Patients Undergoing Restorative Proctocolectomy
5. Non-operative Management of Rectal Cancer after Complete Clinical Response with Neoadjuvant Therapy a Retrospective Study
   Effects of Obesity on Peri-operative Outcomes of Patients Undergoing Resection for Rectal Cancer

New Initiative: The most recent focus of the division is the introduction an enhanced recovery after surgery pathway to colorectal patients.  This initiative is designed to minimize surgical stress and optimize clinical outcomes by standardizing preoperative, perioperative and postoperative interventions using evidence-based care pathways.  The standardization will be initiated by means of increased education and communication interdepartmental in order to include the entire medical team who comes in contact with the patient.

DeMatteo Lab

Gastrointestinal Stromal Tumor (GIST) is the most common human sarcoma. While the small molecule drug imatinib has served as the paradigm for tyrosine kinase inhibition and has been effective in GIST, most patients will eventually develop drug resistance and disease progression. Our lab prioritizes the use of multiple immunocompetent genetically engineered mouse models of GIST to study in vivo tumor biology and immunology. The goal of our lab is to develop novel therapies, with a particular focus on immunotherapy, to overcome imatinib resistance. Multiple therapies identified in our mouse models have been translated into clinical trials for GIST patients.

Ronald P. DeMatteo, MD. FACS - Principal Investigator
DeMatteoLab@pennmedicine.upenn.edu
Room 446A, Stemmler Hall, 3450 Hamilton Walk

Our research is made possible with generous donations from the David Foundation, Betsy Levine Brown and Marc Brown, and the GIST Cancer Research Fund. 

Dr. DeMatteo is the John Rhea Barton Professor and Chairman of Surgery at the University of Pennsylvania. He has trained over twenty surgical residents in his laboratory who have gone into academic careers in Surgical Oncology. Dr. DeMatteo earned his undergraduate degree from The Johns Hopkins University and his medical degree from the Weill Medical College of Cornell University. He completed his residency in General Surgery at the University of Pennsylvania and then a fellowship in Surgical Oncology at Memorial Sloan Kettering Cancer Center. Dr. DeMatteo served as the principle investigator on three national trials for the adjuvant drug imatinib in GIST following surgery, which has led to its approval for adjuvant use by the FDA and became the standard of care.

Current lab members

• Ferdinando Rossi
  Senior Scientist
• Susan Zeng
  Senior Scientist
• Hyunjee Kwak
  UPenn Fellow
• Katherine Tardy
  UPenn Fellow
• Kevin Do
  Research Technician
• Laura Wang
  Research Technician

Open position

Post-Doctoral Researcher Position Available

Careers at Penn

Resident applications

We are now accepting applications from surgical residents to join our basic and translational research lab. Residents will spend a minimum of 2 years studying GIST and tumor immunology under the mentorship of Dr. DeMatteo. Funding is provided.

All interested applicants should send a cover letter and CV to Andrew.Tieniber@Pennmedicine.upenn.edu

Previous lab members 

Previous scientist

Susan Zeng (2010-2017), Senior Scientist, Emory University

Previous fellows

Mark Etherington (2018-2020) University of Pennsylvania, Resident

Marion Liu (2017-2019) Cornell University, Resident

Gerardo Vitiello (2016-2018) University of New York, Resident

Timothy Bowler (2016-2018) Regeneron Pharm Inc, Medical Director

Benjamin Medina (2015-2017), Memorial Sloan Kettering Cancer Center, Fellow

Jennifer Zhang (2014-2017), Memorial Sloan Kettering Cancer Center, Fellow

Adam Levy (2014-2015), UCLA School of Medicine, Fellow

Michael Beckman (2013-2015), Carolinas Medical Center, Attending

Juan Santamaria (2013-2015), University of Nebraska Medical Center, Assistant Professor of Surgery

Adrian Seifert (2012-2015), Asklepios-ASB Klinik Radeberg, Senior Physician

Noah Cohen (2012-2014), Mount Sinai, Attending

Jonathan Greer (2011-2014), Johns Hopkins, Attending

Teresa Kim (2011-2013), University of Washington, Seattle, Attending

Eric Sorenson (2010-2013), Intermountain Healthcare, UT, Attending

Michael Cavnar (2009-2012), University of Kentucky, Attending

Lee Ocuin (2008-2011), Carolinas Healthcare System, NC, Attending

Vinod Balachandran (2008-2010), Memorial Sloan Kettering Cancer Center, Attending

Zubin Bamboat (2007-2009), Summit Medical Group, NJ, Attending

Bryan Burt (2006-2008), Baylor University, Attending

George Plitas (2006-2008), Memorial Sloan Kettering Cancer Center, Attending

Hoang Nguyen (2006-2008), Sanford Health, SD, Attending

T. Peter Kingham, Memorial Sloan Kettering Cancer Center, Attending

Jennifer Stableford, Darmouth-Hitchcock, Attending

Umer Chaudhry (2004-2006), Kaiser Permanente Anaheim, CA, Attending

Steve Katz (2003-2005), TriSalus Life Sciences, Chief Medical Officer

Josh Bleier (2002-2004), University of Pennsylvania, Attending

Venu Pillarisetty (2001-2004), University of Washington, Seattle, Attending

George Miller (2000-2002), New York University, Attending

Previous Technicians

Lillian Levin (2019-2021) University of Pennsylvania, Research Specialist B

Mia DiLolle (2018-2019)

Nesteene Param (2016-2018) University of Pennsylvania, Research Specialist

Jennifer Loo (2014-2017), University at Buffalo, Medical Student

Joanna Maltbaek (2014-2016), University of Washington, PhD Candidate

Benjamin Green (2012-2014), Temple University, Medical Student

Megan Crawley (2012-2014), Massachusetts General Hospital, Genetic Counseling

Rachel Popow (2010-2012), Rutgers University, Medical Student

Hebroon Obaid (2008-2010), Stamford, CT, General Surgeon

Alexander Welles (2006-2008) US Army Research Institute of Environmental Medicine

Jesse Raab (2004-2006) University of North Carolina at Chapel Hill, Assistant Professor

Alaap B. Shah (2002-2004)

Svenja Lahrs (2002-2004)

Projects

Gastrointestinal Stromal Tumor (GIST) and the Immune System

Our laboratory discovered that imatinib changes the intratumoral immune environment by activating cytotoxic CD8+ T cells and inducing apoptosis of anti-inflammatory regulatory T cells through the inhibition of tumor-derived Ido. The immune-mediated anti-tumor effects of imatinib are enhanced when combined with immunotherapy such as CTLA-4 blockade, which led to a clinical trial in human GIST patients. Other cells in the tumor microenvironment, including macrophages, DCs, and stromal cells, also mediate tumor growth and destruction. We seek to better understand the role of the immune system in GIST, with the intention of developing novel molecular and immune-based treatment strategies.

GIST and Oncogene Signaling

Nearly 75% of GISTs contain an activating Kit mutation, while 10% have a mutation in platelet derived growth factor receptor alpha (PDGFRa). Imatinib inhibits both Kit and PDGFRa oncoproteins and has improved survival in metastatic GIST, but patients eventually develop resistance and tumor progression. We have studied the effect of imatinib on Kit signaling and on various compensatory oncogene signaling pathways, including MET. Currently, we are interested in the role of endogenous Kit ligand signaling in the presence of a constitutively active mutation with respect to imatinib resistance.

Recent publications

2020

Zhang, Jennifer Q., Benedikt Bosbach, Jennifer K. Loo, Gerardo A. Vitiello, Shan Zeng, Adrian M. Seifert, Benjamin D. Medina, Nesteene J. Param, Joanna H. Maltbaek, Ferdinand Rossi, Cristina R. Antonescu, Peter Besmer, and Ronald P. DeMatteo. 2020. "The V654A Second-site KIT Mutation Increases Tumor Oncogenesis and STAT Activation in a Mouse Model of Gastrointestinal Stromal Tumor." Oncogene, 39.49: 7153-165.

Moral, John Alec, Joanne Leung, Luis A. Rojas, Jennifer Ruan, Julia Zhao, Zachary Sethna, Anita Ramnarain, Billel Gasmi, Murali Gururajan, David Redmond, Gokce Askan, Umesh Bhanot, Ela Elyada, Youngkyu Park, David A. Tuveson, Mithat Gönen, Steven D. Leach, Jedd D. Wolchok, Ronald P. DeMatteo, Taha Merghoub, and Vinod P. Balachandran. 2020. "ILC2s Amplify PD-1 Blockade by Activating Tissue-specific Cancer Immunity." Nature, 579.7797: 130-35.

2021

Liu, Mengyuan, Mark S. Etherington, Andrew Hanna, Benjamin D. Medina, Gerardo A. Vitiello, Timothy G. Bowler, Nesteene J. Param, Lillian Levin, Ferdinand Rossi, and Ronald P. DeMatteo. 2021. "Oncogenic KIT Modulates Type I IFN–Mediated Antitumor Immunity in GIST." Cancer Immunology Research.

Ye, Shuai, Dinara Sharipova, Marya Kozinova, Lilli Klug, Jimson D’Souza, Martin G. Belinsky, Katherine J. Johnson, Margret B. Einarson, Karthik Devarajan, Yan Zhou, Samuel Litwin, Michael C. Heinrich, Ronald DeMatteo, Margaret Von Mehren, James S. Duncan, and Lori Rink. 2021. "Identification of Wee1 as a Target in Combination with Avapritinib for Gastrointestinal Stromal Tumor Treatment." JCI Insight, 6.2.

Doug Fraker, MD

There are two main areas of basic research occurring in the laboratory of Dr. Douglas Fraker. Both areas relate to his interest in regional treatment of advanced cancers.

1. The first area of research involves the use of melphalan with acidic perfusate. We have developed an animal model in which isolated limb perfusion (ILP) is performed on nude rats that have been xenografted with human melanoma, sarcoma, and colon carcinoma. In each of these tumors, a change in the pH of the perfusate from 7.4 to between 6.8 and 6.9 markedly enhances the tumor response to melphalan, and in fact, the majority of tumors undergo a complete regression. In addition, in limbs with xenografted melanoma, levels of nitric oxide have been found to be increased after perfusion with acidic media, and this effect is seen only in limbs that have xenografted tumor (tumor specific). It is believed that this burst of nitric oxide may play an important role in the enhanced tumor response that is seen. Specifically, since nitric oxide is a powerful modulator of vessels, it is believed that the tumor vasculature may be negatively affected by the acute increase in nitric oxide levels. Another mechanism that has been postulated to explain the effect of acidic perfusate includes the induction of apoptosis of tumor cells by the higher levels of nitric oxide. These potential mechanisms are currently being investigated both in vitro and in vivo in our animal model. Ultimately, it is hoped that the mechanisms for the enhanced tumor response with acidic perfusate may be delineated and eventually used in clinical trials and treatment.
2. The second area of study is related to our ongoing clinical project of intraperitoneal photodynamic therapy for carcinomatosis and sarcomatosis of the abdomen. We currently have studies that involve the analysis of tissue specimens taken during clinical surgery and the development of an animal model to investigate the use of new photosensitizers.

Giorgos C. Karakousis, MD

Dr. Karakousis's translational research primarily focuses on identifying and validating new biomarkers for melanoma. These include immune prognostic markers in the lymph system in the context of new and emerging immunotherapies. He is working toward this end in collaboration with pathologists, immunologists and basic scientists in the context of the Melanoma Spore program. He recently served as co-investigator on a clinical trial testing anti-PD1 therapy for resectable stage III/IV melanoma, and is principal investigator for a soon to be initiated peri-operative anti-PD1 therapy trial for patients with stage IIB/C melanoma as well as for the tissue collection protocol for melanoma at Penn. He is also involved in studies evaluating the use of photoacoustic imaging for detecting micrometastases from melanoma and the prognostic significance of circulating melanoma cells and DNA in patients with advanced melanoma. Finally, he is involved in numerous clinical research projects involving, sarcomas, melanomas, gastric cancer, and advanced peritoneal malignancies.

Rachel Kelz, MD

Visit The Center for Surgery and Health Economics research website.

Robert S. Krouse, MD, MS

Current research efforts include:

1. Principal Investigator of an NCI-funded multi-site study (R01 CA204193-A1 Ostomy Telehealth Self-management Training for Cancer Survivors) testing the benefit of a telehealth-delivered curriculum for cancer survivors with ostomies.
2. Working with teams in Birmingham, AL and Los Angeles, CA to examine the effects of trust on surgical outcomes, focusing on African-American patients. His team is also exploring the association of trust and health-literacy.
3. Led a SWOG study with unique design examining the optimal treatment approach for malignant bowel obstruction (S1316). This study has completed accrual, and data is currently being analyzed.
4. Involved with several efforts examining the effects of depression on patients with advanced cancer.
5. Working on multiple studies examining GI function and dietary and/or physical activity interventions.

The Department of Surgery at the University of Pennsylvania Perelman School of Medicine has established a T32 Training Program in Surgical Oncology Research that is funded by the National Cancer Institute. The program supports surgical residents who will conduct two years of full-time research in basic, translational, or clinical (e.g. health services research, disparities, and clinical trials) research focusing on cancer-related topics. The trainee will work directly with an NIH-funded mentor of their choosing at the University of Pennsylvania. The program includes a robust educational component. There are multiple opportunities to obtain a master’s degree, such as in health policy research, epidemiology, biostatistics, or translational research. A two-year commitment is mandatory.

We seek candidates who embrace and reflect diversity in the broadest sense. The University of Pennsylvania is an Equal Opportunity Employer. 

Program goals and activities

The goal of the T32 program is to train surgeon-scientists in the scientific method in order to make meaningful contributions to cancer research during their academic career. Trainees will participate in didactics, seminars, and journal clubs and complete a course in the Responsible Conduct of Research (RCR). The T32 trainee will not have clinical responsibilities.

Eligibility

• Resident in good standing in an ACGME-approved surgery training program within the United States. Typically, the resident will have completed 2-3 years of clinical, surgical training.
• Ability to perform 2 consecutive years of full-time research.
• U.S. citizen or permanent resident as per NIH stipulations.
• The applicant may not have already received >1 year of support from another T32 or an individual NIH award.

Program mentors - basic/translational

Steven Albelda, MD - My research interests focus on developing novel approaches to the treatment of mesothelioma, lung cancers, and other thoracic malignancies. My clinical interests are primarily in thoracic oncology. In 1992, I founded a translational “Thoracic Oncology Research Laboratory” aimed at moving research from “bench to bedside”. I have led an NCI-funded Program Project aimed at developing new treatments for mesothelioma for the past 22 years. The major areas of recent interest in the lab have been augmentation of anti-tumor immune effects, the tumor microenvironment, mechanisms of T cell dysfunction, and adoptive T cell transfer. To study these, my lab has developed a wide variety of animal models of lung cancer and mesothelioma that can be used to evaluate new therapies and T cell function. We have also analyzed human samples from many clinical trials. The lab has extensive experience in lentiviral transduction of human T cells and retroviral transduction of mouse T cells for use in adoptive T cell transfer.

I am committed to post-doctoral training since I have trained more than 70 post-doctoral fellows. With respect to this application, I can provide training in the following broad areas that are associated with tumor immunology including he tumor microenvironment, lung cancer and mesothelioma biology and carcinogenesis. Having mentored on a T32 for the last 20 years of my career, I understand the commitment and the path to success for these trainees.

Selected publications

1. Singhal S, Standanlick J, Annunziata M, Rao A, Bhojjagarwala P, O’Brien S, Moon EK, Cantu E, Danet-Desnoyers G, Ra H-J, Litzky L, Akimova T, Beier UH, Hancock, Albelda SM, Eruslanov EB. Human tumor-associated monocytes/macrophages and their regulation of the tumor-specific effector Tcell responses in early-stage lung cancer: role of macrophage- versus tumor-expressed PD-L1. Science Translational Med, 2018, 13:11(479)
2. O’Brien SM, Klampatsa A, Thompson JC, Martinez MC, Hwang WT, Rao AS, Standalick JE, Kim S, Cantu E, Litzky LA, Singhal S, Eruslanov E, Moon EK, Albelda SM. Function of Human Tumor-Infiltrating Lymphocytes in Early Stage Non-Small Cell Lung Cancer. Cancer Immunology Research, 2019 7:896-909. PMID 31053597.
3. Wang E, Wang LC, Tsai CY, Gershenson Z, Moon E, Newick K, Sun J, Lo A, Baradet T, Feldman MD, Barrett D, Pure E, Albelda S, Milone MC. Generation of potent T-cell immunotherapy for cancer using DAP12-based, multichain, chimeric immunoreceptors. Cancer Immunol Res. 3:815-26. 2015. PMCID: PMC25941351.
4. Newick K, O’Brien S, Sun J, Kapoor V, Maceyko S, Lo A, Pure E, Moon E, Albelda SM. Augmentation of CAR T cell trafficking and antitumor efficacy by blocking protein kinase A (PKA) localization. Cancer Immunology Research, 6:541-51, 2016 PMCID: PMC4891259

Edward Delikatny, PhD - I have over 25 years' experience in molecular imaging in tumor cells and animal models especially with regard to alterations in lipid metabolism associated with apoptotic cell death due to anticancer drugs. Much of our recent research is based on the development of near-infrared fluorescent contrast agents for detection of metabolism in vivo and for surgical margin detection. We have synthesized molecular imaging probes for detection of tumor microenvironment pH using Cerenkov imaging, activatable probes for detection of phospholipases and probes for detection of choline kinase. The choline kinase sensors are based on a unique design in which a NIR fluorophore is modified to contain a choline mimetic group that interacts directly with the enzyme active site and functions as a competitive inhibitor. We have shown that these probes can report on the level of choline kinase expression in breast tumor models and can monitor the response to anticancer therapy in vivo. For purposes of this T32 training grant, I have been working with surgeons for the last 5 years and have multiple joint publications with Dr. Sunil Singhal (Associate Program Director of the proposal and with Dr. David Holt, a veterinary oncology surgeon from the School of Veterinary Medicine. I have worked closely with surgical residents (Jarrod Predina, Andrew Newton) over the last 3 years, so I feel comfortable training future residents.

I am committed to training and have mentored many candidates, two current graduate students, one who successfully defended his Ph.D. thesis in Aug. 2019, one postdoc who is now an Associate Professor in Radiology at UTSW; a research technician who is in his final year of the MD/PhD program at the University of Rochester, and six undergraduate students in Penn’s Summer Undergraduate Internship (SUIP) program. Three of my SUIP students entered graduate school at Penn and one at Harvard. One of these recently defended her thesis and is now doing postdoctoral studies. One SUIP student has completed medical school, and the sixth is employed at the Broad Institute of MIT and Harvard.

Selected publications

1. Arlauckas, S.P., Kumar, M., Popov, A.V., Poptani, H. and Delikatny, E.J. (2017). Near infrared fluorescent imaging of choline kinase alpha expression and inhibition in breast tumors. Oncotarget 8, 16518-16530.
2. Arlauckas, S.P., Popov, A.V. and Delikatny, E.J. (2016). Choline kinase alpha - Putting the ChoK-hold on tumor metabolism. Prog Lipid Res. 63, 28-40. PMCID: PMC5360181
3. Judy, R., Keating, J., DeJesus, E., Jiang, J., Okusanya, O., Nie, S., Holt, D., Arlauckas, S., Low, P., Delikatny, E.J. and Singhal, S. (2015). Quantification of tumor fluorescence during Intraoperative optical cancer imaging. Scientific Reports. 5, 16208. PMCID: PMC4643322
4. Keating, J., Newton, A., Venegas, O., Nims, S., Zeh, R., Predina, J., Deshpande, C., Kucharczuk, J., Nie, S., Delikatny, E.J., Singhal, S. (2017). Near-Infrared intraoperative molecular imaging can locate metastases to the lung. Ann. Thorac. Surg. 103: 390-398.

Ronald DeMatteo, MD (Program Principal Investigator) - I am the Program Director of the proposed T32 Surgical Oncology Research Training Program. I became the Chair of Surgery at the Perelman School of Medicine at the University of Pennsylvania two years ago. I am a physician scientist who was appointed to the staff at Memorial Sloan Kettering Cancer Center in 1999. There, I was the Vice Chair of the Department of Surgery from 2006-17 and had a Joint Appointment in the Immunology Program of Sloan Kettering Institute. I was the Program Director of the clinical Surgical Oncology fellowship for 7 years and have mentored over 100 fellows. I won a departmental teaching award in 2017. In my laboratory, I have trained over 30 surgery residents. Furthermore, I was the Associate Program Director of the T32 in Surgical Oncology at Memorial Sloan Kettering from 2006-12, and then became the Principal Investigator for the competitive renewal that covered the period 2012-17.

I specialize in the treatment of hepatopancreatobiliary cancers and gastrointestinal stromal tumor (GIST). While I have performed research in liver immunology and inflammation, my primary focus has been on the molecular, immunologic, and clinical aspects of gastrointestinal stromal tumor (GIST). GIST is the most common type of sarcoma and it arises from the gastrointestinal tract. We have created a large collaborative team involving a sarcoma pathologist, molecular biologist, bioinformatics expert, and medical oncologists. We have developed several genetically engineered mouse models of GIST and have routine access to fresh human GIST surgical specimens from consenting patients. We have translated several of our laboratory findings into clinical trials. A CTEP Phase I trial of dasatinib and ipilimumab for advanced GIST has been completed.

Unexpectedly, we discovered that part of the efficacy of imatinib in GIST depended on inhibition of indoleamine 2,3-dioxygenase (IDO), an immunosuppressive protein made by many tumors. We found that imatinib and the immune agent anti-CTLA-4 were synergistic in a genetically engineered mouse model. Furthermore, to our knowledge, we were the first group to freshly isolate intratumoral macrophages from a human cancer and subject them to detailed phenotypic, molecular, and functional analyses. We determined that intratumoral macrophages in human GISTs were highly dynamic as they were actually anti-tumoral at baseline, became pro-tumoral after imatinib therapy, and reverted to anti-tumoral upon imatinib resistance. The mechanism was mediated by C/EBP transcription factors and the findings have implications for the clinical application of macrophage-directed therapy. Recently, we found that the immune response to GIST depends on the driver mutation. In addition, imatinib inhibits intratumoral dendritic cell development, resulting in less active anti-tumoral T cells.

Selected publications

1. Balachandran VP, Cavnar MJ, Zeng S, Bamboat ZM, Ocuin LM, Obaid H, Sorenson EC, Ariyan C, Rossi F, Besmer P, Guo T, Antonescu CR, Taguchi T, Yuan J, Wolchok JD, Allison JP, DeMatteo RP. Imatinib mesylate potentiates anti-tumor T cell responses in gastrointestinal stromal tumor through the inhibition of Ido. Nat Med 2011; 17:1094-100. PMCID:PMC3278279
2. Cavnar MJ, Zeng S, Kim TS, Sorenson EC, Ocuin LM, Balachandran VP, Seifert AM, Greer JB, Popow R, Crawley MH, Cohen NA, Green BL, Rossi F, Besmer P, Antonescu CR, DeMatteo RP. KIT oncogene inhibition drives intratumoral macrophage M2 polarization. J Exp Med 2013; 210:2873-86. PMCID: PMC3865475
3. Vitiello GA*, Bowler TG*, Liu M, Medina BD, Zhang JQ, Param NJ, Loo JK, Goldfeder RL, Chibon F, Rossi F, Zeng S, DeMatteo RP. Differential immune profiles distinguish the mutational subtypes of gastrointestinal stromal tumor. J Clin Invest 2019. Epub. PMID30762585
4. Medina BD, Vitiello GA, Seifert AM, Zeng S, Liu M, Bowler T, Zhang JQ, Cavnar MJ, Loo JK, Param NJ, Maltbaek JH, Rossi F, Balachandran VP, DeMatteo RP. Oncogenic kinase inhibition limits Batf3-dependent dendritic cell development and anti-tumor immunity. J Exp Med 2019. Epub. PMID:31000683

Evgeniy Eruslanov, PhD - For the last decade, I have been studying tumor immunology. Specifically, I have been investigating the role of inflammatory myeloid cells in the tumor microenvironment and mechanisms by which tumors modulate their immune functions. My ultimate research goal is to develop novel approaches that will enhance endogenous immune response in order to break tumor-induced tolerance/suppression and to improve the efficacy of immunotherapy for lung cancer. I have been working with surgeons and surgical residents for over one decade, so I am delighted to act as a mentor for future surgical oncology residents as part of this T32 training grant. Although I have not trained surgical residents, my master’s and PhD trainees have been hired at top universities such as Harvard and UPenn.

Selected publications

1. Singhal S, Stadanlick J, Annunziata MJ, Rao AS, Bhojnagarwala PS, O'Brien S, Moon EK, Cantu E, Danet-Desnoyers G, Ra HJ, Litzky L, Akimova T, Beier UH, Hancock WW, Albelda SM, Eruslanov E. Human tumor-associated monocytes/macrophages and their regulation of T cell responses in early-stage lung cancer. Science Translational Medicine. 2019, Feb 13; 11(479).
2. Singhal S, Bhojnagarwala P, O’Brien S, Moon E, Garfall A, Rao A,. Quatromoni J, Stephen T, Litzky L, Deshpande D, FeldmanM, HancockW, Conejo-Garcia J, Albelda S, and Eruslanov E. Origin and Role of a Subset of Tumor-Associated Neutrophils with Antigen Presenting Cell Features in Early-Stage Human Lung Cancer. Cancer Cell, 2016, Jun 30.
3. Eruslanov E, Bhojnagarwala P, Quatromoni J, Stephen T, Ranganathan A, Deshpande C, Akimova T, Vachani A, Litzky L, Hancock W, Conejo-Garcia J, Feldman M, Albelda S, and Singhal S. Tumorassociated neutrophils stimulate T cell responses in early-stage human lung cancer. The Journal of Clinical Investigation, 2014, Dec 1; 124(12): 5466-80.
4. Eruslanov E, Stoffs T, Kim W, Daurkin I, Gilbert S, Su LM, Vieweg J, Daaka Y, and Kusmartsev S. Expansion of CCR8+ inflammatory myeloid cells in cancer patients with urothelial and renal carcinomas. Clinical Cancer Research. 2013, Apr 1; 19(7): 1670-80.

Malay Haldar, MD, PhD - My laboratory studies how tumor microenvironment regulates the differentiation and function of innate immune cells of the mononuclear phagocyte system (MP cells), which comprises of monocytes, dendritic cells (DC), and macrophages. MP cells perform diverse function; from controlling immune responses to maintaining tissue homeostasis. This functional diversity is reflected in their phenotypic and developmental heterogeneity. Tissueassociated factors are thought to control the influx, differentiation, and function of MP cell subsets, which is underscored by their dramatic redistribution in tissues under various pathological states. Our laboratory is interested in: (1) how tumor-associated MP cells contribute to tissue homeostasis and pathological states and (2) pathways controlling the development of distinct tumor-associated MP cell subsets. In the context of human diseases, we are particularly interested in solid tumors. Tumor-infiltrating MP cells can shape the immunosuppressive tumor microenvironment, which is a major barrier to immunotherapy. We are investigating the bi-directional cross-talk between tumor microenvironment and MP cells that generates this immunosuppressive milieu with the overarching goal of targeting these cells for immunotherapy. In our approach, we integrate data from genetically engineered mouse models, patient-derived samples, basic molecular biology, and high dimensional immune and genomic profiling to generate and test hypothesis.

I have been training residents for the last 4 years, and in fact, currently have a surgical resident in my laboratory who is pursuing his PhD. I am confident that I can prepare surgeons to be the highest caliber academic Surgical Oncologists for the coming decades.

Selected publications

1. Haldar M, Hancock JD, Coffin CM, Lessnick SL, Capecchi MR. A conditional mouse model of synovial sarcoma: insights into amyogenic origin. Cancer Cell. (2007) PMID: 17418413
2. Haldar M, Hedberg ML, Hockin MF, Capecchi MR. A CreER-based random induction strategy for modeling translocation-associated sarcomas in mice. Cancer Research. (2009) PMID: 19351831, PMCID: PMC2906130
3. Jones KB, Barrott JJ, Xie M, Haldar M, Jin H, Zhu JF, Monument MJ, Mosbruger TL, Langer EM, Randall RL, Wilson RK, Cairns BR, Ding L, Capecchi MR. The Impact of chromosomal translocation locus and fusion oncogene coding sequence in synovial sarcomagenesis. Oncogene. (2016) PMID: 26947017, PMCID: PMC5014712
4. Haldar M, Karan G, Tvrdik P, Capecchi MR. Two cell lineages, myf5 and myf5-independent, participate in mouse skeletal myogenesis. Developmental Cell. (2008). PMID: 18331721

Gerald Linette, MD, PhD - My primary interest is human cancer immunology. My graduate studies concentrated on HIV-1 immunobiology. Since 1996, I have been actively involved in the development of new therapeutic approaches for melanoma, including dendritic cell vaccines, gene therapy, adoptive T cell therapy, and checkpoint inhibitors. My laboratory research is comprised of various trainees including clinical fellows, post-doctoral fellows, graduate students, undergraduates as well as senior research investigators with specialization in molecular biology and cellular immunology. We are a member of the Center for Cellular Immunotherapies and the Parker Institute for Cancer Immunotherapy at Penn. As part of a larger clinical multidisciplinary effort, I serve as the principle investigator for consortium and investigator-initiated clinical trials. My current research focus is the identification of MHC class I restricted neoantigens encoded by various malignancies and implementation of new cell therapy approaches for melanoma and other solid tumors. Our group employs next generation sequencing technologies through active collaborations with experts in genomics, proteomics, and bioinformatics. Given my extensive experience with training fellows and residents, I would be honored to train Surgical Oncologist as part of the T32 Training Grant in Surgical Oncology proposed by the Department of Surgery and Dr. Ron DeMatteo.

Selected publications

1. Linette GP, Hartzman RJ, Ledbetter JA, June CH.: HIV-1 infected T cells show a selective signaling defectafter perturbation of CD3/antigen receptor. Science 1988 Jul 29; 241(4865): 573-6. PMID:2899908.
2. Linette GP, Grusby MJ, Hedrick SM, Hansen TH, Glimcher LH, Korsmeyer SJ. Bcl-2 is upregulated at the CD4+ CD8+ stage during positive selection and promotes thymocyte differentiation at several control points. Immunity 1994 Jun;1(3):197-205. PMID: 7889408.
3. Carreno BM, Magrini V, Becker-Hapak M, Kaabinejadian S, Hundal J, Petti AA, Ly A, Lie WR, Hildebrand WH, Mardis ER, Linette GP. Cancer immunotherapy. A dendritic cell vaccine increases the breadth and diversity of melanoma neoantigen-specific T cells. Science. 2015 May 15;348(6236):803-8. PMID: 25837513.
4. Migliorini D, Dietrich PY, Stupp R, Linette GP, Posey AD, June CH. CAR T cell therapies in glioblastoma: a first look. Clin Cancer Res. 2017 Nov 20. pii: clincanres.2871.2017. doi: 10.1158/1078-0432.CCR-17-2871. PMID: 29158268.

Sunil Singhal, MD (Track Leader) - The fundamental question of my research is: “After a curative cancer surgery, why do some patients still develop recurrences?” I hypothesize patients who undergo surgery develop relapses for two fundamental reasons: (i) micrometastatic disease in the local wound bed, and (ii) failures in the host immune system that prevent systemic disease. Furthermore, I postulate that the optimal time to cure cancer patients is during the time of surgery because they have the least quantity of residual disease. To study this hypothesis, I have developed two simultaneous research efforts. Over the last 10 years, I have built both research programs. I have NIH funding to support both programs, and my mixed bibliography will attest to these efforts. First, I study methods of molecular imaging “intraoperative molecular imaging”) to identify residual tumor cells in the wound bed after surgery. Ultimately, if surgeons can perform a better surgery, the likelihood of a local recurrence and an inadequate staging should diminish. Second, I have pursued a more detailed examination of the immune factors that exist at the time of surgery, and why these factors fail to prevent systemic relapses despite minimal residual disease. If these perioperative immune elements can be mapped, then the use of tumor immunotherapy during this golden period of reduced tumor burden may be a solution to prevent systemic recurrences.

Selected publications

1. Predina JD, Eruslanov E, Judy B, Kapoor V, Cheng GJ, Wang S, Sun J, Fridlender G, Albelda SM, Singhal S. “Changes in the Local Tumor Microenvironment in Recurrent Cancers May Explain the Failure of Vaccines after Surgery.” Proceedings of the National Academy of Sciences. 110(5): E415-24. Jan 29, 2013. PMCID: PMC3562776.
2. Eruslanov E, Bhojnagarwala PS, Quatromoni JG, Stephen TL, Ranganathan A, Deshpande C, Akimova T, Vachani A, Litzky L, Hancock WW, Conejo-Garcia JR, Feldman M, Albelda SM, Singhal S. “Inflammatory Tumor-associated Neutrophils in Early Stage Human Lung Cancer.” Journal of Clinical Investigation. 124(12):5466-80. December 1, 2014. PMCID: PMC4348966.
3. Singhal S, Bhojnagarwala PS, O’Brien S, Moon EK, Garfall AL, Rao A, Quatromoni JG, Stephen TL, Litzky L, Deshpande C, Feldman M, Hancock WW, Conejo-Garcia JR, Albelda SM, Eruslanov EB. “Origin and Role of a Subset of Tumor-Associated Neutrophils with Antigen Presenting Cell Features (Hybrid TANs) in Early-Stage Human Lung Cancer.” Cancer Cell. 2016. PMCID: PMC4945447
4. Singhal S, Stadanlick J, Annunziata MJ, Rao AS, Bhojnagarwala PS, O’Brien S, Moon EK, Cantu E, Danet-Desnoyers G, Ra HJ, Litzky L, Akimova T, Beier UH, Hancock WW, Albelda SM, Eruslanov EB. “Human tumor-associated monocytes/macrophages and their regulation of the tumor-specific effector T cell responses in early-stage lung cancer: role of macrophage- versus tumor-expressed PD-L1.” Science Translational Medicine. (11) 479, 2019.

Robert Vonderheide, MD, DPhil - I am the Director of the Abramson Cancer Center and the John H. Glick, MD Abramson Cancer Center’s Director Professor at the University of Pennsylvania. I am considered an international leader in pancreatic cancer immunobiology. I co-lead a SU2C Team on Pancreatic Cancer Immunotherapy. My laboratory combines efforts in both basic research and clinical investigation to advance the understanding of tumor immunology and to develop novel immunotherapies for cancer. The basic research focus in my laboratory includes deciphering the immunobiology of novel genetically engineered mouse models of cancer, including the regulation of immune surveillance and the tumor microenvironment by CD40. My translational work tests novel approaches such as vaccines, antibodies, and adoptive T cells for the treatment of patients with pancreatic cancer, breast cancer and melanoma. I have also studied ‘universal’ tumor antigens such as hTERT and immune modulatory pathways involving CD40, GM-CSF, CXCR2, PD-1, CTLA-4, and CD25.

I have a significant experience in training residents, and I have trained over 50 postdocs in my career. A large portion of them are in academic positions with their own NIH grants. Therefore, I am confident that if a surgical resident chooses my lab, they will be well prepared to do rigorous scientific research in their own careers.

Selected publications

1. Vonderheide RH, Hahn WC, Schultze JL, Nadler LM (1999). The telomerase catalytic subunit is a widely expressed tumor-associated antigen recognized by cytotoxic T lymphocytes. Immunity 10(6):673-679.
2. Clark CE, Hingorani SR, Mick R, Combs C, Tuveson DA, Vonderheide RH (2007). Dynamics of the immune reaction to pancreatic cancer from inception to invasion. Cancer Res 67(19):9518-9527.
3. Bayne LJ, Beatty GL, Jhala N, Clark CE, Rhim AD, Stanger BZ, Vonderheide RH (2012). Tumor-derived granulocyte-macrophage colony-stimulating factor regulates myeloid inflammation and T cell immunity in pancreatic cancer. Cancer Cell 21(6):822-835. PMCID: PMC3575028
4. Vonderheide RH, Flaherty KT, Khalil M, Stumacher MS, Bajor DL, Hutnick NA, Sullivan P, Mahany JJ, Gallagher M, Kramer A, Green SJ, O'Dwyer PJ, Running KL, Huhn RD, Antonia SJ (2007). Clinical activity and immune modulation in cancer patients treated with CP-870,893, a novel CD40 agonist monoclonal antibody. Clin Cancer Res 25(7):876-883.

Program mentors - clinical

Justin Bekelman, MD - I am a practicing radiation oncologist and physician-scientist with expertise in clinical epidemiology and health services research. My research programs focus on two themes: cancer comparative effectiveness and delivery system and payment reform, integrating methods from the fields of epidemiology, clinical trials, health economics and public policy. In cancer comparative effectiveness research, my research employs several methodological approaches to conduct randomized and non-randomized studies addressing important evidence gaps in cancer care. My research group has also developed and applied tools to mitigate the limitations of non-randomized studies of cancer interventions, using traditional regression, instrumental variable, and causal inference methods. I am the PI of a large-budget R01-level multi-center pragmatic randomized clinical trial comparing proton to photon radiation therapy for breast cancer enrolling at over 60 US treatment centers and funded by the Patient-Centered Outcomes Research Institute. In delivery system and payment reform research, I conduct observational, quasi-experimental and randomized studies to identify and characterize low-value cancer care and to develop and evaluate interventions to promote high-value cancer care, with a particular emphasis on how financial and non-financial incentives affect provider behavior. In summary, my expertise, skills, experience, and supportive environment have prepared me to successfully serve as XXXX on this proposed research.

Selected publications

1. Bekelman JE, Sylwestrzak G, Barron J, Liu J, Epstein AJ, Freedman G, Malin J, Emanuel EJ. Uptake and Costs of Hypofractionated vs. Conventional Whole Breast Irradiation After Breast Conserving Surgery in the United States, 2008 – 2013. JAMA. 2014 Dec 17;312(23):2542-50. PMID: 25494006.
2. Bekelman JE, Halpern SD, Blankart CR, Bynum JP, Cohen J, Fowler R, Kaasa S, Kwietniewski L, Melberg HO, Onwuteaka-Philipsen B, Oosterveld-Vlug M, Pring A, Schreyögg J, Ulrich CM, Verne J, Wunsch H, Emanuel EJ. Comparison of Site of Death, Health Care Utilization, and Hospital Expenditures for Patients Dying With Cancer in 7 Developed Countries. JAMA. 2016 Jan 19;315(3):272-283. PMID: 26784775.
3. Ojerholm E, Halpern SD, Bekelman JE. Default options: opportunities to improve quality and value in oncology. J Clin Oncol. 2016 34(16):1844-71847.
4. Bekelman JE and Joffe S. Three Steps Toward a More Sustainable Path for Targeted Cancer Drugs. JAMA. 2018 Jun 5;319(21):2167-2168.

Angela Bradbury, MD - As a medical oncologist with specialized training in clinical cancer genetics, cancer prevention, and medical ethics, I have been developing and leading translational genetic research focused on the clinical implementation of genetic medicine to promote the health of individuals, families, and communities since 2003. This includes research evaluating novel delivery models to facilitate dissemination and implementation of cancer genetics and evaluation of the psychosocial and behavioral outcomes of genetic testing (R01 CA160847-01A1 and R21CA164121-02), studies evaluating the outcomes with return of multiplex genetic research results for breast cancer susceptibility (ACRA 2013, R01 CA190871) and the impact of genetic and familial risk on children, adolescents, and families (R01 CA138819 Daly/Bradbury, Basser Center for BRCA1/2 Research). Many of these studies have incorporated eHealth approaches to delivery of genetic services for cancer and Alzheimer’s disease, including telephone and videoconferencing delivery (R01 CA160847 and R21CA164121-02, UF1AG046150), as well as Internet Genetic Education Delivery to facilitate informed decision-making regarding receipt of individual genetic research results (R01 CA190871, COMET ancillary study to MATCH). Each of these studies or subprojects has been under my leadership. Equally important, I have been providing clinical care to individuals at high risk for cancer and patients receiving cancer genetics services for over 10 years. Thus, my experience as an independent physician-scientist, ongoing research program and strong collaborative relationships provide the experience and expertise to lead the proposed research.

Selected publications

1. Patrick-Miller L, Egleston B, Daly MB, Stevens E, Fetzer D, Forman A, Bealin L, Rybak C, Peterson C, Corbman M, Bradbury AR. Implementation and outcomes of telephone disclosure of clinical BRCA1/2 test results. Patient Education and Counseling. 2013 Dec;93(3):413-9. PMID: 24075727. PMCID:PMC4199583.
2. Bradbury AR, Patrick-Miller L, Long J, Powers J, Stopfer J, Forman A, Rybak C, Mattie K, Brandt A, Chambers R, Chung WK, Churpek J, Daly MB, Digiovanni LD, Farengo-Clark D, Fetzer D, Ganschow P, Grana G, Gulden C, Hall M, Kohler L, Maxwell K, Merrill S, Montgomery S, Mueller R, Nielsen S, Olopade O, Rainey K, Seelaus C, Nathanson KL, Domchek SA. Development of a Tiered and Binned Genetic Counseling Model for Informed Consent in the Era of Multiplex Testing for Cancer Susceptibility. Genetics in Medicine 2015, 17(6):485-92. PMID: 25297947. PMCID: PMC4983405.
3. Bradbury AR, Olopade OI, Dignam JJ, Ibe CN, Auh SL, Hlubocky FJ, Cummings SA, White MA, Daugherty CK. How often do mutation carriers tell their young children of the family’s risk for cancer? A study of parental disclosure of BRCA mutations to minors and young adults. Journal of Clinical Oncology 25 (24): 3705-11, 2007. PMID:17704419.
4. Terry MB, Bradbury AR. Family-based Breast Cancer Prevention Efforts in Adolescence. Pediatrics 2016 Nov: 138 (Suppl 1):S78-S80.PMID: 27940980.

Angela DeMichele, MD, MSCE - I am a breast cancer oncologist, trialist and clinical epidemiologist. My research focuses on the development of investigational therapeutics, identifying biomarkers predictive of outcome/response to therapy and development of novel approaches to treat minimal residual disease to prevent recurrence. Nationally, I Co-Chair the ECOG/ACRIN Cooperative Group Breast Committee, am a PI in the Translational Breast Cancer Research Consortium and Chair the Trial Operations Working Group of the I-SPY2 Trial. I am the PI of numerous investigator-initiated clinical trials and translational epidemiologic studies, including nternational Co-PI of the PALLAS Adjuvant Palbociclib Trial). At the University of Pennsylvania Abramson Cancer Center, I Co-Direct the 2-PREVENT Translational Center of Excellence, and Co-Lead the ACC Breast Cancer Program. In these roles, I have built a multidisciplinary, peer-review funded research program and developed translational resources, including a comprehensive biobank and database. In addition, I have trained the next generation of clinical researchers through individual mentorship in Masters in Clinical Epidemiology and development of the Clinical Trials course in the Center for Clinical Epidemiology, Biostatistics and Bioinformatics. My experience and expertise in all aspects of drug and biomarker development and clinical trial design and conduct are especially well suited to developing and implementing the research proposed in this application.

Selected publications

1. Rugo HS, Olopade OI, DeMichele A, Yau C, van 't Veer LJ, Buxton MB, Hogarth M, Hylton NM, Paoloni M, Perlmutter J, Symmans WF, Yee D, Chien AJ, Wallace AM, Kaplan HG, Boughey JC, Haddad TC, Albain KS, Liu MC, Isaacs C, Khan QJ, Lang JE, Viscusi RK, Pusztai L, Moulder SL, Chui SY, Kemmer KA, Elias AD, Edmiston KK, Euhus DM, Haley BB, Nanda R, Northfelt DW, Tripathy D, Wood WC, Ewing C, Schwab R, Lyandres J, Davis SE, Hirst GL, Sanil A, Berry DA, Esserman LJ; I-SPY 2 Investigators. (2016). Adaptive Randomization of Verliparib-Carboplatin Treatment in Breast Cancer. N Engl J Med. 375(1):23-34. PMID:27406347
2. DeMichele A, Clark AS, Kay S Tan KS, Daniel F Heitjan DF, Kristi Gramlich K, Gallagher M, Lal P, Feldman M, Zhang P, Colameco C, Lewis D, Langer M, Goodman N, Domchek SM, Gogineni K, Rosen M, Fox KR, and O'Dwyer P. (2015). CDK 4/6 Inhibitor Palbociclib (PD0332991) in Rb+ Advanced Breast Cancer: Phase II Activity, Safety and Predictive Biomarker Assessment Clin Cancer Res. 21(5):995-1001. PMID: 25501126
3. Mao JJ, Su HI, Feng R, Donelson ML, Aplenc R, Rebbeck TR, Stanczyk F, and DeMichele A. (2011) Association of functional polymorphisms in CYP19A1 with aromatase inhibitor associated arthralgia in breast cancer survivors. Breast Cancer Res 13(1): R8. PMCID: PMC3109575.
4. DeMichele A, Martin A, Mick R, Wray L, Cabral M, Athanasiadis G, Colligan T, Stadtmauer E and Weber B. (2003) Interleukin-6 (IL-6)-174G>C Polymorphism is Associated with Improved Outcome in High Risk Breast Cancer. Cancer Res 63:8051-56.

Rachel Kelz, MD, MSCE (Track Leader) - I am a board-certified general surgeon with formal training in health services research and business. My clinical practice is focused on endocrine and oncologic surgery. Within the Department of Surgery (DOS), I serve as the Vice Chair for Clinical Research and the Founding Director of the Center for Surgery and Health Economics. I am committed to improving surgical quality and eradicating disparities in cancer care through innovative education and scientific investigation. I devoted much of my first seven years on faculty at PENN to education. I was recognized for my contributions to the educational programs with the Gordon P. Buzby Award for Leadership and the Christian R. and the Mary F. Lindback Award for Distinguished Teaching, the most prominent educational award given by the University. More recently, I have focused on multidisciplinary, collaborative research as a mechanism to improve surgical care delivery and outcomes for patients with benign and malignant diseases. As an R01 funded investigator, I am working to establish standards in surgical education and advance health services organization and delivery to improve surgical cancer care. I am a senior scholar at the Leonard Davis Institute. I serve as the Secretary (Executive Board Member) of the Society of Clinical Surgery, a Councilor-at-Large (Executive Council) for the Society of University Surgeons, a Member of the Board of Directors of the Surgical Outcomes Club, and as the Director of the American College of Surgeons National Quality In-Training Initiative. My role as a leader in Surgery, Education, and Health Services Research will facilitate the training of future surgeon-scientists in surgical oncology, and provide a national network for their future growth and development. As witnessed by the successes of my mentees, and recognition from the DOS as a Mentorship Awardee (2014), I have made mentoring junior investigators a priority. As a surgeon-scientist with collaborations across disciplines and universities, and an established track record of mentoring young investigators, I am fully committed to and capable of supporting the training opportunities put forth in the T32 proposal entitled, “Surgical Oncology Research Training Program at Penn”.

Selected publications

1. Dowzicky PM, Shah AA, Barg FK, Eriksen WT, McHugh MD, Kelz RR. An Assessment of Patient, Caregiver, and Clinician Perspectives on the Post-Discharge Phase of Care. Annals of surgery. 2019 Jul.
2. Berger I, Xia L, Wirtalla C, Dowzicky P, Guzzo TJ, Kelz RR. 30-day readmission after radical cystectomy: Identifying targets for improvement using the phases of surgical care. Canadian Urological Association Journal. 2019 Jul;13(7):E190.
3. Sharoky CE, Collier KT, Wirtalla CJ, Sinnamon AJ, Neuwirth MG, Kuo LE, Roses RE, Fraker DL, Karakousis GC, Kelz RR. Hospitalization in the year preceding major oncologic surgery increases risk for adverse postoperative events. Annals of surgical oncology. 2017 Nov 1;24(12):3477-85.
4. Bailey EA, Hoffman RL, Wirtalla C, Karakousis G, Kelz RR. Development and validation of a prediction model for patients discharged to post–acute care after colorectal cancer surgery. Surgery. 2017 Apr 1;161(4):1049-57.

Robert Krouse, MD - My current research program focuses primarily on cancer survivorship, including palliative care. My years of clinical experience as a Surgical Oncologist are an added benefit as a clinical researcher. I have a long history with inter-disciplinary research, leading and participating in teams that include surgeons, nursing researchers, epidemiologists, anthropologists, health economists, psychologists, nutritionists, physiologists, basic scientists, and statisticians. I have mentored 4 medical students, 11 residents, and 11 pre- and post-doctoral researchers. For this application, I can provide training in broad areas in Surgical Oncology Research including comparative effectiveness, patient-centered outcomes, palliative care, quality of life, mixed methods, clinical trials and cooperative group research. As Advisor to the SWOG Cancer Survivorship Committee, and Co-Chair of the developing SWOG Palliative and End-of-Life Care Committee, I help initiate, shepherd, and complete national trials related to cancer survivorship and palliative care issues. There are multiple studies at different levels of development that I have played a significant role with and will continue in the future. Presently I am Principal Investigator and national lead on an AHRQ-funded grant (AHRQ HS021491, Prospective Comparative Effectiveness Trial for Malignant Bowel Obstruction) which is in collaboration with SWOG cooperative group (S1316). This study has a novel hybrid design to examine the optimal treatment approach for patients with malignant bowel obstruction. Related to cancer survivorship, our team has had a focus primarily on rectal cancer survivorship and has established a greater understanding of long-term health-related quality of life (HRQOL) issues. We are currently designing interventions to improve the HRQOL for these survivors and their families. One current project I lead is a PCORI-funded grant (PCORI 1507-31690, Ostomy Telehealth for Cancer Survivors), which uses telehealth to provide an ostomy self-management curriculum to cancer survivors with ostomies. It is designed with patient-centered outcomes and is based on cancer survivor input from both a pilot study and from previous HRQOL studies on patient-identified challenges related to living with an ostomy. A related study I lead is an NIH-funded grant (R01 CA204193, Ostomy Telehealth Selfmanagement Training for Cancer Survivors) delivering the curriculum to rural populations. We are in the initial stages of planning an implementation study utilizing the NCORP system as an accrual base in conjunction with SWOG and other NCTN sites.

Selected publications

1. Grant M, Ferrell B, Dean G, Uman G, Chu D, Krouse R. Revision and psychometric testing of the City of Hope Quality of Life-Ostomy Questionnaire. Qual Life Res. 2004 Oct;13(8):1445-57. PubMed PMID: 15503840.
2. Krouse RS, Herrinton LJ, Grant M, Wendel CS, Green SB, Mohler MJ, Baldwin CM, McMullen CK, Rawl SM, Matayoshi E, Coons SJ, Hornbrook MC. Health-related quality of life among long-term rectal cancer survivors with an ostomy: manifestations by sex. J Clin Oncol. 2009 Oct 1;27(28):4664-70. PubMed PMID: 19720920; PubMed Central PMCID: PMC2754912.
3. Grant M, McCorkle R, Hornbrook MC, Wendel CS, Krouse R. Development of a chronic care ostomy selfmanagement program. J Cancer Educ. 2013 Mar;28(1):70-8. PubMed PMID: 23104143; PubMed Central PMCID: PMC3578127.
4. Wendel CS, Grant M, Herrinton L, Temple LK, Hornbrook MC, McMullen CK, Bulkley JE, Altschuler A, Krouse RS. Reliability and validity of a survey to measure bowel function and quality of life in long-term rectal cancer survivors. Qual Life Res. 2014 Dec;23(10):2831-40. PubMed PMID: 24890826; PubMed Central PMCID: PMC4236297.

Jason Moore, PhD - I have a strong track record developing, evaluating and applying statistical, machine learning and artificial intelligence algorithms and software for identifying genetic, genomic and proteomic biomarkers of clinical traits such as autoimmune disease. A central focus has been on developing translational bioinformatics methods such as multifactor dimensionality reduction (MDR) that embrace, rather than ignore, the complexity of human pathobiology. In addition to an NIH-funded translational bioinformatics research program, I serve as Director of the Institute for Biomedical Informatics and Senior Associate Dean for Informatics at the Perelman School of Medicine of the University of Pennsylvania. I also serve as Editor-in-Chief of the journal BioData Mining. I have trained more than 50 undergraduate, 20 graduate, and 15 postdoctoral students. I have previously served as the director of an interdisciplinary graduate training program at Dartmouth where I also led an NIH K25 training grant as PI. I am currently PI of an NHGRI T32 training grant. I will use these leadership and education experiences to assist with this training program.

Selected publications

1. Ritchie MD, Hahn LW, Roodi N, Bailey LR, Dupont WD, Parl FF, Moore JH (2001). Multifactordimensionality reduction reveals high-order interactions among estrogen-metabolism genes in sporadic breast cancer. Am J Hum Genet. 69(1):138-47. PMC1226028.
2. Hu T, Sinnott-Armstrong NA, Kiralis JW, Andrew AS, Karagas MR, Moore JH (2011). Characterizing genetic interactions in human disease association studies using statistical epistasis networks. BMC Bioinformatics 12:364, PMC3215301.
3. Askland K, Read C, Moore JH (2009). Pathways-based analyses of whole-genome association study data in bipolar disorder reveal genes mediating ion channel activity and synaptic neurotransmission. Hum Genet. 125(1):63-79. PMID: 19052778.
4. Darabos C, White MJ, Graham BE, Leung DN, Williams SM, Moore JH. (2014a). The multiscale backbone of the human phenotype network based on biological pathways. BioData Min. 7(1):1. PMC3924922.

Katherine Nathanson, MD - I am an internationally recognized physician-scientist cancer geneticist/genomicist. Clinically, I manage patients with inherited cancer susceptibility syndromes, mainly those associated with brain, skin renal and neuroendocrine tumors. My research focuses on the elucidation of the inherited and somatic genetics of cancer, specifically in pheochromocytomas/paragangliomas (PCC/PGL), testicular germ cell tumors (TGCT), melanoma, and hereditary breast and ovarian cancers; I have over 300 publications in all these areas, with an H-score of 66. I am highly dedicated to training and education at all levels. I am the program director for the combined Internal Medicine/Clinical Genetics program at Penn Medicine, and MPI of a T32 post-doctoratraining grant in Genomic Medicine from NHGRI. I serve on the Residency Committee for Medical Genetics, on the admissions committee for the MD-PhD program and as co-PI for the Medical Genetics Research Training Grant. I also am a member of the Cancer Biology section of the Cell and Molecular Biology, and Genomics and Computational Biology graduate groups, serving on the latter’s admissions committee. I am highly committed to training and have trained 12 post-doctoral fellows, who have been very successful in obtaining funding and faculty positions. Within the past five years, five of my trainees have moved onto academic positions – Assistant Professors at the University of Pennsylvania, New York University and the University of Colorado, Denver, MD Anderson Cancer Center, and Director of Gynecologic Oncology Research at Christiana Care Health System, Delaware. With respect to this application, I can provide training in the area of inherited and somatic cancer genetics and genomics as associated with Surgical Oncology Research.

Selected publications

1. Maxwell KN, Hart SN, Vijai J, Schrader KA, Slavin TP, Thomas T, Wubberhorst B, Ravichandran V, Moore RM, Hu C, Guidugli L, Wenz B, Domchek SM, Robson ME, Szabo C, Neuhausen SL, Weitzel JN, Offit K, Couch FJ, Nathanson KL. Evaluation of ACMG-guideline-based variant classification of cancer susceptibility and non-cancer-associated genes in families affected by breast cancer. Am J Hum Genet, 2016 May 5;98(5):801-17. PMID:27153395 PMCID:PMC4863474.
2. Kanetsky PA, Mitra N, Vardhanabhuti S, Li M, Vaughn DJ, Letrero R, Ciosek SL, Doody DR, Smith LM, Weaver J, Albano A, Chen C, Starr JR, Rader DJ, Godwin AK, Reilly MP, Hakonarson H, Schwartz SM, Nathanson KL. Common variation in KITLG and at 5q31.3 proximate to SPRY4 predispose to testicular germ cell cancer. Nat Genet 2009; 41(7):811-5. PMCID:PMC2865677
3. Bollag G, Hirth P, Tsai J, Zhang J, Ibrahim PN, Cho H, Spevak W, Zhang C, Zhang Y, Habets G, (25 authors) Chapman PB, Flaherty KT, Xu X, Nathanson KL, Nolop K: Clinical efficacy of a RAF inhibitor needs broad target blockade in BRAF-mutant melanoma. Nature 2010 Sep 30;467(7315):596-9. PMCID:PMC2948082
4. Gordon JD, Lal P, Dondeti VR, Letrero R, Parekh KN, Oquendo CE, Greenberg RA, Flaherty KT, Rahmell K, Keith B, Simon MC, Nathanson KL. HIFα effects on c-Myc distinguish two subtypes of sporadic VHL-deficient clear cell renal carcinoma. Cancer Cell 2008;14(6):435-46. PMCID:PMC2621440

Salary and expenses

How to apply

Please send the following 3 items.

1. Cover Letter
   (the letter should include):
   1. Career objectives
   2. Prior research experience
   3. Area of interest within cancer research
   4. Training goals for the T32 fellowship including whether you have interest in obtaining an advanced degree
   5. Proposed mentor (if decided) from the list of existing mentors above. You may propose a mentor at Penn not currently involved in the T32 program.
2. Updated CV
3. Letters of recommendation

Solicit a letter of recommendation from the Department Chair and the Residency Program Director regarding your career potential and the ability to commit to 2 years of research at Penn. It is acceptable to submit separate letters, or a single letter signed by both.

Applications should be submitted as a SINGLE PDF file to:

Kara Lehman (Kara.Lehman@pennmedicine.upenn.edu)

For more information

Please contact Ronald P. DeMatteo MD, Chair of Surgery, at Ronald.Dematteo@pennmedicine.upenn.edu

Daniel A. Hashimoto, MD, MTR

Daniel A. Hashimoto, MD, MTR is assistant professor of surgery at the Hospital of the University of Pennsylvania (HUP) and director of PCASO. He is a foregut and endoscopic surgeon and translational surgical data scientist. He is co-founder and vice chair of the board for the Global Surgical AI Collaborative. His primary research interests are in applications of computer vision to intraoperative surgical decision making and the development of automated feedback mechanisms for surgical trainees. He is an ardent believer in multidisciplinary education and enjoys working closely with both surgical trainees and engineering/CS students.

Visit the Penn Computer Assisted Surgery and Outcomes (PCASO) Laboratory.

Steven E. Raper, MD, JD, MA (Hon)

Steven E. Raper, MD, JD, MA is particularly interested in informed consent, a legal contract between the physician and the patient. For the past several years he has been pursuing the process of bringing the Department of Surgery on line with procedure-specific consent forms and electronic consent allowing the forms to be completely done within the EPIC electronic medical record platform. Proper informed consent is both an event – the signature of the surgeon and patient (or surrogate) – and a process of communication of the necessary elements of a proposed operation between surgeon and patient. The electronic consent process he has spearheaded for the past few years enhances and improves both the event and the process. Looking ahead, he sees informed consent as one part of a health law curriculum that he hopes to introduce into legal and medical education as well as the performance of empiric studies on how to further improve the process.

The following scholarly papers are the most recent that he feels best describe my intense interest in writing and teaching about how to combine law and surgery:

1. Raper SE, Joseph J, Seymour WG, Sullivan PG. Tipping the scales: educating surgeons about medical malpractice. J Surg Res. 2016 Nov;206(1):206-213. doi: 10.1016/j.jss.2016.08.002. This work arose from a course I taught surgery faculty on basic information about medical malpractice. The course had five parts: the basics of medical malpractice; the cost of malpractice insurance; current departmental claims experience; strategies for decreasing the risk of being named in a claim; and, an overview of malpractice reforms. An anonymous seven question survey was cast in a five point Likert scale format. A weighted average of 4.5 or above was considered satisfactory. Two free text questions asked about positive and negative aspects of the course.
2. Raper SE, An Artless Tale: Challenges Faced in Clinical Research. Food and Drug Law J. 2016;71(1):59-104. I identified and provided ideas on how to face four foundational challenges associated with the design and conduct of novel research trials and specifically a gene transfer trial in which a subject died. First, regarding calculation of the risk to benefit ratio; we ultimately chose a group of relatively asymptomatic adults after first considering a seriously ill group of newborns. Second, communication with the agencies of the Food and Drug Administration (FDA) and the National Institutes of Health (NIH), as well as local Institutional Review Boards (IRB); relevant aspects of 45 CFR 46 (the Common Rule) and FDA regulations with regard to conduct of clinical trials and difficulties in communication are highlighted. Third, issues of research consent. At the time, I considered research consent to be similar to standard clinical consent. But the two should be categorized differently. Lastly, the challenge of irreconcilable conflict of interest between investigator and subject in clinical research.
3. Raper SE, Fleisher LA, Mayer DL, Ferman RV; Steele K, Hollway J Using root cause analysis to study prosecutorial error: a collaboration between the Montgomery County (Pennsylvania) District Attorney’s office and the Quattrone Center for the Fair Administration of Justice. 62 Villanova Law Review Tolle Lege 13-40. In a criminal investigation related to the alleged rape of an unconscious victim, members of the investigative team misread a laboratory report.  The interpretive error was presented during a court proceeding.  In order to learn from this error, and in furtherance of the prosecutor’s ethical obligations of (a) conviction integrity, (b) transparency and accountability, and (c) a culture of continuous self-improvement within the Office, the District Attorney partnered with the interdisciplinary Quattrone Center for the Fair Administration of Justice at the University of Pennsylvania Law School to conduct a Root Cause Analysis (RCA) of the error.  The goal of the RCA was to identify specific activities, policies, procedures, and environmental factors that allowed the error to occur, and to implement changes that would prevent similar errors from occurring in the future.
4. Raper SE, Rose D, Nepps ME, Drebin JA. Taking the Initiative: Risk-Reduction Strategies and Decreased Malpractice Costs. J Am Coll Surg. 2017 Nov;225(5):612-621. To heighten awareness of attending and resident surgeons regarding strategies for defense against malpractice claims, a series of risk reduction initiatives have been carried out in our Department of Surgery. We hypothesized that emphasis on certain aspects of risk might be associated with decreased malpractice costs. The relative impact of Department of Surgery initiatives was assessed when compared with malpractice experience for the rest of the Clinical Practices of the University of Pennsylvania (CPUP). Surgery and CPUP malpractice claims, indemnity, and expenses were obtained from the Office of General Counsel. Malpractice premium data were obtained from CPUP finance. The Department of Surgery was assessed in comparison with all other CPUP departments. Cost data (yearly indemnity and expenses), and malpractice premiums (total and per physician) were expressed as a percentage of the 5 year mean value preceding implementation of the initiative program. Surgery implemented 38 risk reduction initiatives. Faculty participated in 27 initiatives; house staff participated in 10 initiatives; and advanced practitioners in 1 initiative. Department of Surgery claims were significantly less than CPUP (74.07% vs 81.07%; p < 0.05). The mean yearly indemnity paid by the Department of Surgery was significantly less than that of the other CPUP departments (84.08% vs 122.14%; p < 0.05). Department of Surgery-paid expenses were also significantly less (83.17% vs 104.96%; p < 0.05), and surgical malpractice premiums declined from baseline, but remained significantly higher than CPUP premiums. The data suggest that educating surgeons on malpractice and risk reduction may play a role in decreasing malpractice costs. Additional extrinsic factors may also affect cost data. Emphasis on risk reduction appears to be cumulative and should be part of an ongoing program.

Dr. Raper's Law School experiences have also provided a further cross-disciplinary opportunity. As Vice-Chair for Quality and Risk Management for the Department of Surgery he has been involved in the various forms of medical error reduction in the wake of To Err is Human. He was fortunate to be directed to the Quattrone Center for the Fair Adminstration of Justice and the Center’s Executive Director John Hollway, by Law Professor Stephanos Bibas (now on the Federal Court of Appeals Third Circuit), yet another of his teachers, specifically in Criminal Procedure (from bail to jail). He has been able to help translate many of the principles of error reduction used in medicine into the law. As a result, he has been able to participate in several Quattrone-sponsored symposia and contribute a well-received lecture to Professor Hollway’s Convictions Integrity seminar. Dr. Raper aspires to get this course cross-listed next year with the Medical School. He has also lent his expertise to a Root Cause Analysis of a high profile case in Montgomery County as well as a similar analysis of the Lex Street massacre with the Philadelphia Police department. He is currently learning how to use the powerful social sciences coding software nVivo to code transcripts from Convictions Integrity Units across the country and to assist with the development of a statement on the Best Practices for such units. This work is directly analogous to similar concepts used in medicine; and think it will be useful in the simulation work done in communication skills.

Dr. Raper has no funded projects; the choice of study would be up to the resident. He would like for the residents to enroll in Penn’s Master in Law degree, specifically in the Health Law Track. Interested residents should contact him via email.

Alan W. Flake, MD - ongoing research

Alan W. Flake, MD, his lab performs research on prenatal stem cell and gene therapy, essentially trying to cure every disease that's able to be diagnosed in utero. Current stem cell projects include treatment for immunodeficiency syndromes, hemophilia, sickle cell, and myelomeningocele. Current gene therapy projects include treatment for multiple neurodegenerative diseases, epidermolysis bullosa, and breast cancer (via BRCA).

Visit the Center for Fetal Diagnosis and Treatment website.

Penn has developed one of the most robust and active plastic surgery clinical research programs in the country under the established guidance of our attending physicians: 

Clinical research fellowship

The Clinical Research Fellowship in the Division of Plastic Surgery at the University of Pennsylvania is a 12-month funded fellowship dedicated to patient related research. There have been 23 research fellows since the inception of the position in 2008. Research fellows are either senior medical students or general surgery residents. The research fellowship is an outstanding opportunity for those applying into plastic surgery, and a great help to the clinical research endeavors within the research group.

Position description

The Clinical Research Fellows’ broad responsibilities include organizing and gaining approval for the majority of the research that is produced within the division. This includes developing project ideas, grant proposals, and IRB protocols, if necessary. It also includes the prospective and retrospective management and statistical analysis of several large databases, including one of the largest and most detailed autologous breast reconstruction databases in the field.

Although no formal bio-statistical or clinical research training is funded through the fellowship, the Clinical Research Fellows gain a tremendous amount of on-the-job training from residents and previous fellows who are accomplished academic researchers in plastic surgery. The fast-paced environment and abundance of practical training leaves Clinical Research Fellows with a robust knowledge of the current state of academic literature in their areas of interest within plastic surgery, as well as an ability to effectively explore this literature, develop new ideas, and gather, manage, and analyze institution and national datasets to answer novel hypotheses.

At the end of the year, a Clinical Research Fellow is expected to be involved in the completion of 20+ clinical research ideas and submit them for publication, many to high-impact plastic and general surgery journals. At any one given time, a Clinical Research Fellow may be responsible for directly overseeing 5-10 projects, some of which he or she will complete during their tenure and others of which he or she will pass on to the next fellow(s). In this manner, the fellows learn to create reproducible and scientifically valid data in a collaborative environment, thereby setting the foundation for many of the skills they will need throughout their academic careers.

Applying

To apply for fellowship please complete application.
Applications will be accepted until November 1, 2025.

Resident Research Portal (intranet only)

Current clinical research fellows

2025-2026

• Maggie Hornick, MD
• Aamirah McCutchen, MD
• Timothy Olsen, MD

Previous clinical research fellows

2024-2025

• Maggie Hornick
• Salman Khan
• Malia Voytik

2023-2024

• Mehdi Lemdani
• Jane Nguyen

2022-2023

• Harrison Davis
• Theodore Habarth

2021-2022

• Abhishek Desai
• Ankoor Talwar

2020-2021

• Adrienne Christopher
• Martin Morris

2019-2020

• Jessica Cunning
• Arturo Rios Diaz

2018-2019

• Geoff Kozak
• Shelby Nathan

2017-2018

• Fabiola Enriquez
• Jaclyn Mauch
• Irfan Rhemtulla

2016-2017

• Martin Carney

2016-2017

• Jason Weissler

2015-2016

• Michael Lanni

2015-2016

• Michael Tecce

2014-2015

• Andrew R. Bauder

2014-2015

• Jonathan R. Sarik

2013-2014

• Marten N. Basta

2012-2013

• Ari M. Wes

2011-2012

• Carrie A. Stransky

2010-2011

• Michael N. Mirzabeigi

2009-2010

• Jonas A. Nelson

2008-2009

• Joshua Fosnot

Areas of active research

Clinical research in the Division of Plastic Surgery at the University of Pennsylvania investigates a broad range of topics in plastic and general surgery. Our residents, fellows, and students are continually developing new research endeavors and arranging intra- and inter-institution collaborations. The majority of this research can be divided into the broad categories depicted here. Please click on an area of interest to find out more about the latest investigations in this area and recent publications. Contact information is also listed for each area of interest. Please do not hesitate to get in touch to find out more or get involved with the Penn Plastic Surgery Research Group.

Autologous breast reconstruction

The plastic surgery faculty at Penn performs autologous breast reconstructions for well over 200 patients a year, forming one of the most clinically active programs in the country. This flurry of clinical activity forms a wealth of data for research inquiries. Every patient who receives breast reconstruction is logged into a prospectively maintained database, allowing for numerous intra-institution studies. In tandem, our researchers have based several lines of investigation on national datasets, employing advanced statistics to track longitudinal outcomes, cost and subsequently validate their models.

Selected Publications

1. Fischer, J. P., Nelson, J. A., Cleveland, E., Sieber, B., Rohrbach, J. I., Serletti, J. M., Kanchwala, S. Breast reconstruction modality outcome study: a comparison of expander/implants and free flaps in select patients. Plast Reconstr Surg 2013;131:928-934.
2. Fischer, J. P., Nelson, J. A., Sieber, B., Cleveland, E., Kovach, S. J., Wu, L. C., Serletti, J. M., Kanchwala, S. Free tissue transfer in the obese patient: an outcome and cost analysis in 1258 consecutive abdominally based reconstructions. Plast Reconstr Surg 2013;131:681e-692e.
3. Fischer, J. P., Sieber, B., Nelson, J. A., Cleveland, E., Kovach, S. J., Wu, L. C., Kanchwala, S., Serletti, J. M. Comprehensive outcome and cost analysis of free tissue transfer for breast reconstruction: an experience with 1303 flaps. Plast Reconstr Surg 2013;131:195-203.
4. Fischer, J. P., Wes, A. M., Nelson, J. A., Basta, M., Rohrbach, J. I., Wu, L. C., Serletti, J. M., Kovach, S. J. Propensity-matched, longitudinal outcomes analysis of complications and cost: comparing abdominal free flaps and implant-based breast reconstruction. J Am Coll Surg 2014;219:303-312.
5. Wink, J. D., Fischer, J. P., Nelson, J. A., Serletti, J. M., Wu, L. C. Direct-to-implant breast reconstruction: An analysis of 1612 cases from the ACS-NSQIP surgical outcomes database. J Plast Surg Hand Surg 2014;48:375-381.
6. Wes, A. M., Cleveland, E., Nelson, J. A., Fischer, J. P., Kovach, S. J., Kanchwala, S., Serletti, J. M., Wu, L. C. Do Prior Abdominal Surgeries Increase Complications in Abdominally Based Breast Reconstructions? Ann Plast Surg 2014.
7. Nelson, J. A., Stransky, C. A., Fischer, J. P., Fosnot, J., Serletti, J. M., Wu, L. C. Reexamining free flap breast reconstruction in the community and university setting: is there a difference? Ann Plast Surg 2014;73 Suppl 2:S171-174.
8. Nelson, J. A., Fischer, J. P., Yan, C., Fosnot, J., Selber, J. C., Wu, L. C., Serletti, J. M., Kanchwala, S. The impact of obesity on abdominal wall function after free autologous breast reconstruction. Microsurgery 2014;34:352-360.
9. Nelson, J. A., Fischer, J. P., Radecki, M. A., Pasick, C., McGrath, J., Serletti, J. M., Wu, L. C. Delayed autologous breast reconstruction: factors which influence patient decision making. J Plast Reconstr Aesthet Surg 2013;66:1513-1520.
10. Nelson, J. A., Fischer, J. P., Pasick, C., Nelson, P., Chen, A. J., Fosnot, J., Selber, J. C., Wu, L. C., Serletti, J. M. Chronic pain following abdominal free flap breast reconstruction: a prospective pilot analysis. Ann Plast Surg 2013;71:278-282.
11. Nelson, J. A., Fischer, J. P., Grover, R., Mirzabeigi, M. N., Nelson, P., Wes, A. M., Au, A., Serletti, J. M., Wu, L. C. Intraoperative perfusion management impacts postoperative outcomes: An analysis of 682 autologous breast reconstruction patients. J Plast Reconstr Aesthet Surg 2014.
12. Nelson, J. A., Fischer, J. P., Grover, R., Cleveland, E., Erdmann-Sager, J., Serletti, J. M., Wu, L. C. The impact of anemia on microsurgical breast reconstruction complications and outcomes. Microsurgery 2014;34:261-270.
13. Nelson, J. A., Fischer, J. P., Chung, C. U., Fosnot, J., Selber, J. C., Serletti, J. M., Wu, L. C. Preoperative anemia impacts early postoperative recovery following autologous breast reconstruction. J Plast Reconstr Aesthet Surg 2014;67:797-803.
14. Grover, R., Nelson, J. A., Fischer, J. P., Kovach, S. J., Serletti, J. M., Wu, L. C. The impact of perforator number on deep inferior epigastric perforator flap breast reconstruction. Archives of plastic surgery 2014;41:63-70.
15. Fosnot, J., Fischer, J. P., Smartt, J. M., Jr., Low, D. W., Kovach, S. J., 3rd, Wu, L. C., Serletti, J. M. Does previous chest wall irradiation increase vascular complications in free autologous breast reconstruction? Plast Reconstr Surg 2011;127:496-504.
16. Fischer, J. P., Wes, A. M., Tuggle, C. T., Wu, L. C. Venous thromboembolism risk in mastectomy and immediate breast reconstruction: analysis of the 2005 to 2011 American College of Surgeons National Surgical Quality Improvement Program data sets. Plast Reconstr Surg 2014;133:263e-273e.
17. Fischer, J. P., Wes, A. M., Tuggle, C. T., Nelson, J. A., Tchou, J. C., Serletti, J. M., Kovach, S. J., Wu, L. C. Mastectomy with or without immediate implant reconstruction has similar 30-day perioperative outcomes. J Plast Reconstr Aesthet Surg 2014;67:1515-1522.
18. Fischer, J. P., Wes, A. M., Tuggle, C. T., Serletti, J. M., Wu, L. C. Risk analysis and stratification of surgical morbidity after immediate breast reconstruction. J Am Coll Surg 2013;217:780-787.
19. Fischer, J. P., Wes, A. M., Tuggle, C. T., 3rd, Serletti, J. M., Wu, L. C. Risk analysis of early implant loss after immediate breast reconstruction: a review of 14,585 patients. J Am Coll Surg 2013;217:983-990.
20. Fischer, J. P., Wes, A. M., Kanchwala, S., Kovach, S. J. Effect of BMI on modality-specific outcomes in immediate breast reconstruction (IBR)--a propensity-matched analysis using the 2005-2011 ACS-NSQIP datasets. J Plast Surg Hand Surg 2014;48:297-304.
21. Fischer, J. P., Nelson, J. A., Au, A., Tuggle, C. T., 3rd, Serletti, J. M., Wu, L. C. Complications and morbidity following breast reconstruction--a review of 16,063 cases from the 2005-2010 NSQIP datasets. J Plast Surg Hand Surg 2014;48:104-114.
22. Fischer, J. P., Nelson, J. A., Kovach, S. J., Serletti, J. M., Wu, L. C., Kanchwala, S. Impact of obesity on outcomes in breast reconstruction: analysis of 15,937 patients from the ACS-NSQIP datasets. J Am Coll Surg 2013;217:656-664.
23. Fischer, J. P., Nelson, J. A., Mirzabeigi, M. N., Serletti, J. M., Kanchwala, S. Perioperative hemodynamics in free flap breast reconstruction: incidence, predictors, and management of tachycardia. Ann Plast Surg 2012;69:356-360.
24. Fischer, J. P., Nelson, J. A., Serletti, J. M., Kanchwala, S. Breast reconstruction in the morbidly obese patient: assessment of 30-day complications using the 2005 to 2010 national surgical quality improvement program data sets. Plast Reconstr Surg 2014;133:882e-883e.
25. Fischer, J. P., Nelson, J. A., Serletti, J. M., Wu, L. C. Peri-operative risk factors associated with early tissue expander (TE) loss following immediate breast reconstruction (IBR): a review of 9305 patients from the 2005-2010 ACS-NSQIP datasets. J Plast Reconstr Aesthet Surg 2013;66:1504-1512.
26. Fischer, J. P., Nelson, J. A., Sieber, B., Stransky, C., Kovach, S. J., Serletti, J. M., Wu, L. C. Transfusions in autologous breast reconstructions: an analysis of risk factors, complications, and cost. Ann Plast Surg 2014;72:566-571.
27. Fischer, J. P., Tuggle, C. T., Au, A., Kovach, S. J. A 30-day risk assessment of mastectomy alone compared to immediate breast reconstruction (IBR). J Plast Surg Hand Surg 2014;48:209-215.
28. Lu, S. M., Nelson, J. A., Fischer, J. P., Fosnot, J., Goldstein, J., Selber, J. C., Serletti, J. M., Wu, L. C. The impact of complications on function, health, and satisfaction following abdominally based autologous breast reconstruction: a prospective evaluation. J Plast Reconstr Aesthet Surg 2014;67:682-692.
29. Nelson, J. A., Guo, Y., Sonnad, S. S., Low, D. W., Kovach, S. J., 3rd, Wu, L. C., Serletti, J. M. A Comparison between DIEP and muscle-sparing free TRAM flaps in breast reconstruction: a single surgeon's recent experience. Plast Reconstr Surg 2010;126:1428-1435.
30. Del Corral, G. A., Wes, A. M., Fischer, J. P., Serletti, J. M., Wu, L. C. Outcomes and Cost Analysis in High-Risk Patients Undergoing Simultaneous Free Flap Breast Reconstruction and Gynecologic Procedures. Ann Plast Surg 2014.
31. Selber, J. C., Bergey, M., Sonnad, S. S., Kovach, S., Wu, L., Serletti, J. M. Free flap breast reconstruction in advanced age: is it safe? Plast Reconstr Surg 2009;124:1015-1022.
32. Selber, J. C., Nelson, J. A., Ashana, A. O., Bergey, M. R., Bristol, M. N., Sonnad, S. S., Serletti, J. M., Wu, L. C. Breast cancer screening prior to cosmetic breast surgery: ASPS members' Adherence to American Cancer Society Guidelines. Plast Reconstr Surg 2009;124:1375-1385.
33. Jandali, S., Wu, L. C., Vega, S. J., Kovach, S. J., Serletti, J. M. 1000 consecutive venous anastomoses using the microvascular anastomotic coupler in breast reconstruction. Plast Reconstr Surg 2010;125:792-798.
34. Selber, J. C., Fosnot, J., Nelson, J., Goldstein, J., Bergey, M., Sonnad, S., Serletti, J. M. A prospective study comparing the functional impact of SIEA, DIEP, and muscle-sparing free TRAM flaps on the abdominal wall: Part II. Bilateral reconstruction. Plast Reconstr Surg 2010;126:1438-1453.
35. Selber, J. C., Nelson, J., Fosnot, J., Goldstein, J., Bergey, M., Sonnad, S. S., Serletti, J. M. A prospective study comparing the functional impact of SIEA, DIEP, and muscle-sparing free TRAM flaps on the abdominal wall: part I. unilateral reconstruction. Plast Reconstr Surg 2010;126:1142-1153.
36. Mirzabeigi, M. N., Au, A., Jandali, S., Natoli, N., Sbitany, H., Serletti, J. M. Trials and tribulations with the inferior gluteal artery perforator flap in autologous breast reconstruction. Plast Reconstr Surg 2011;128:614e-624e.
37. Mirzabeigi, M. N., Sbitany, H., Jandali, S., Serletti, J. M. The role of postoperative antibiotics in reducing biofilm-related capsular contracture in augmentation mammaplasty. Plast Reconstr Surg 2011;128:34e-35e.
38. Sbitany, H., Serletti, J. M. Acellular dermis-assisted prosthetic breast reconstruction: a systematic and critical review of efficacy and associated morbidity. Plast Reconstr Surg 2011;128:1162-1169.
39. Serletti, J. M., Fosnot, J., Nelson, J. A., Disa, J. J., Bucky, L. P. Breast reconstruction after breast cancer. Plast Reconstr Surg 2011;127:124e-135e.
40. Mirzabeigi, M. N., Lee, M., Smartt, J. M., Jr., Jandali, S., Sonnad, S. S., Serletti, J. M. Extended trimethoprim/sulfamethoxazole prophylaxis for implant reconstruction in the previously irradiated chest wall. Plast Reconstr Surg 2012;129:37e-45e.
41. Mirzabeigi, M. N., Wang, T., Kovach, S. J., Taylor, J. A., Serletti, J. M., Wu, L. C. Free flap take-back following postoperative microvascular compromise: predicting salvage versus failure. Plast Reconstr Surg 2012;130:579-589.
42. Nelson, J. A., Kim, E. M., Eftekhari, K., Low, D. W., Kovach, S. J., Wu, L. C., Serletti, J. M. Late venous thrombosis in free flap breast reconstruction: strategies for salvage after this real entity. Plast Reconstr Surg 2012;129:8e-15e.
43. Nelson, J. A., Nelson, P., Tchou, J., Serletti, J. M., Wu, L. C. The ethnic divide in breast reconstruction: a review of the current literature and directions for future research. Cancer treatment reviews 2012;38:362-367.
44. Nelson, J. A., Tchou, J., Domchek, S., Sonnad, S. S., Serletti, J. M., Wu, L. C. Breast reconstruction in bilateral prophylactic mastectomy patients: factors that influence decision making. J Plast Reconstr Aesthet Surg 2012;65:1481-1489.
45. Sbitany, H., Mirzabeigi, M. N., Kovach, S. J., Wu, L. C., Serletti, J. M. Strategies for recognizing and managing intraoperative venous congestion in abdominally based autologous breast reconstruction. Plast Reconstr Surg 2012;129:809-815.
46. Wang, T. Y., Serletti, J. M., Cuker, A., McGrath, J., Low, D. W., Kovach, S. J., Wu, L. C. Free tissue transfer in the hypercoagulable patient: a review of 58 flaps. Plast Reconstr Surg 2012;129:443-453.
47. Wang, T. Y., Serletti, J. M., Kolasinski, S., Low, D. W., Kovach, S. J., Wu, L. C. A review of 32 free flaps in patients with collagen vascular disorders. Plast Reconstr Surg 2012;129:421e-427e.

Abdominal wall reconstruction

Ventral hernia is a widely prevalent and heavily burdensome problem from the patient, provider, and healthcare system perspectives. As one of our most active clinical and research areas at Penn, our endeavors in complex abdominal wall reconstruction are numerous and varied. A few of our primary areas of interest include outcomes, cost-utility, and health related quality of life. Recent publications have focused on risk-assessment and stratification for patient selection and preoperative counseling with regards to morbidity and the placement of prophylactic mesh. We have also attempted to better characterize the impact of this disease state through targeted market research and survey administration. Other studies have ranged from cost containment to intraoperative strategies to optimize postoperative outcomes. Finally, several studies in this area pair with our active research in autologous breast reconstruction by describing the changes in the abdominal wall after autologous breast reconstruction.

Selected publications

1. Mirzabeigi MN, Wilson AJ, Fischer JP, Basta M, Kanchwala S, Kovach SJ, Serletti JM, Wu LC. Predicting and managing donor-site wound complications in abdominally based free flap breast reconstruction: improved outcomes with early reoperative closure. Plast Reconstr Surg. 2015 Jan;135(1):14-23. doi: 10.1097/PRS.0000000000000805. PubMed PMID: 25539292.
2. Basta MN, Fischer JP, Kovach SJ. Assessing complications and cost-utilization in ventral hernia repair utilizing biologic mesh in a bridged underlay technique. Am J Surg. 2015 Apr;209(4):695-702. doi: 10.1016/j.amjsurg.2014.04.017. Epub 2014 Jul 11. PubMed PMID: 25305799.
3. Fischer JP, Basta MN, Wink JD, Wes AM, Kovach SJ. Optimizing patient selection in ventral hernia repair with concurrent panniculectomy: an analysis of 1974 patients from the ACS-NSQIP datasets. J Plast Reconstr Aesthet Surg. 2014 Nov;67(11):1532-40. doi: 10.1016/j.bjps.2014.07.001. Epub 2014 Jul 12. PubMed PMID: 25085825.
4. Fischer JP, Wes AM, Wink JD, Nelson JA, Rohrbach JI, Braslow BM, Kovach SJ. Analysis of perioperative factors associated with increased cost following abdominal wall reconstruction (AWR). Hernia. 2014 Oct;18(5):617-24. doi: 10.1007/s10029-014-1276-y. Epub 2014 Jul 20. PubMed PMID: 25038893.
5. Wink JD, Wes AM, Fischer JP, Nelson JA, Stranksy C, Kovach SJ 3rd. Risk factors associated with early failure in complex abdominal wall reconstruction: A 5 year single surgeon experience. J Plast Surg Hand Surg. 2015 Apr;49(2):77-82. doi: 10.3109/2000656X.2014.903195. Epub 2014 Apr 3. PubMed PMID: 24693869.
6. Nelson JA, Fischer JP, Chung CU, Fosnot J, Selber JC, Serletti JM, Wu LC. Preoperative anemia impacts early postoperative recovery following autologous breast reconstruction. J Plast Reconstr Aesthet Surg. 2014 Jun;67(6):797-803. doi: 10.1016/j.bjps.2014.02.017. Epub 2014 Feb 21. PubMed PMID: 24613772.
7. Lu SM, Nelson JA, Fischer JP, Fosnot J, Goldstein J, Selber JC, Serletti JM, Wu LC. The impact of complications on function, health, and satisfaction following abdominally based autologous breast reconstruction: a prospective evaluation. J Plast Reconstr Aesthet Surg. 2014 May;67(5):682-92. doi: 10.1016/j.bjps.2014.01.017. Epub 2014 Feb 5. PubMed PMID: 24553313.
8. Nelson JA, Fischer JP, Cleveland EC, Wink JD, Serletti JM, Kovach SJ 3rd. Abdominal wall reconstruction in the obese: an assessment of complications from the National Surgical Quality Improvement Program datasets. Am J Surg. 2014
9. Apr;207(4):467-75. doi: 10.1016/j.amjsurg.2013.08.047. Epub 2014 Jan 4. PubMed PMID: 24507860.
   Nelson JA, Fischer JP, Wink JD, Kovach SJ 3rd. A population-level analysis of abdominal wall reconstruction by component separation in the morbidly obese patient: can it be performed safely? J Plast Surg Hand Surg. 2014 Oct;48(5):305-11. doi: 10.3109/2000656X.2014.880350. Epub 2014 Feb 4. PubMed PMID: 24495185.
10. Fischer JP, Wink JD, Nelson JA, Kovach SJ 3rd. Among 1,706 cases of abdominal wall reconstruction, what factors influence the occurrence of major operative complications? Surgery. 2014 Feb;155(2):311-9. doi: 10.1016/j.surg.2013.08.014. PubMed PMID: 24433774.
11. Nelson JA, Fischer JP, Yan C, Fosnot J, Selber JC, Wu LC, Serletti JM, Kanchwala S. The impact of obesity on abdominal wall function after free autologous breast reconstruction. Microsurgery. 2014 Jul;34(5):352-60. doi: 10.1002/micr.22218. Epub 2013 Dec 26. PubMed PMID: 24375437.
12. Fischer JP, Wes AM, Wink JD, Nelson JA, Braslow BM, Kovach SJ. Analysis of risk factors, morbidity, and cost associated with respiratory complications following abdominal wall reconstruction. Plast Reconstr Surg. 2014 Jan;133(1):147-56. doi: 10.1097/01.prs.0000436836.96194.a2. PubMed PMID: 24374674.
13. Fischer JP, Nelson JA, Wes AM, Wink JD, Yan C, Braslow BM, Chen L, Kovach SJ. The use of epidurals in abdominal wall reconstruction: an analysis of outcomes and cost. Plast Reconstr Surg. 2014 Mar;133(3):687-99. doi: 10.1097/01.prs.0000438048.91139.31. PubMed PMID: 24263390.
14. Fischer JP, Shang EK, Butler CE, Nelson JA, Braslow BM, Serletti JM, Kovach SJ. Validated model for predicting postoperative respiratory failure: analysis of 1706 abdominal wall reconstructions. Plast Reconstr Surg. 2013 Nov;132(5):826e-835e. doi: 10.1097/PRS.0b013e3182a4c442. PubMed PMID: 24165634.
15. Cleveland EC, Fischer JP, Nelson JA, Sieber B, Low DW, Kovach SJ 3rd, Wu LC, Serletti JM. Optimizing the fascial closure: an analysis of 1261 abdominally based free flap reconstructions. Ann Plast Surg. 2013 Sep;71(3):255-60. doi: 10.1097/SAP.0b013e318286380e. PubMed PMID: 23945529.
16. Fosnot J, Serletti JM. Discussion: Abdominal wall stability and flap complications after deep inferior epigastric perforator flap breast reconstruction: does body mass index make a difference? Analysis of 418 patients and 639 flaps. Plast Reconstr Surg. 2012 Jul;130(1):34e-35e. doi: 10.1097/PRS.0b013e3182547d77. PubMed PMID: 22743952.
17. Nelson JA, Fosnot J, Selber JC, Wu LC, Serletti JM. Age and abdominal wall strength: assessing the aging abdominal wall after autologous breast reconstruction. Microsurgery. 2013 Jan;33(1):14-23. doi: 10.1002/micr.21984. Epub 2012 Apr 18. PubMed PMID: 22511251.
18. Nelson, J. A., Fischer, J. P., Yan, C., Fosnot, J., Selber, J. C., Wu, L. C., Serletti, J. M., Kanchwala, S. The impact of obesity on abdominal wall function after free autologous breast reconstruction. Microsurgery 2014;34:352-360.

Minimally invasive facial rejuvenation

Our research in the area of minimally invasive facial rejuvenation techniques is new, but growing. Using state of the art imaging, we have performed a number of clinical trials examining the stress and strain of FDA-approved neuromodulators. We are slated to use this same imaging apparatus to examine improvement in skin contour and wrinkle reduction with hyaluronic-based facial fillers. Using objective data, as well as the recently published FACE-Q to evaluate patient response to treatments, we are encouraged that our findings will help significantly affect translational research. In an era where for some the “liquid facelift” is more palatable than surgery, our results could significantly impact the world of facial aesthetics.

Selected publications

1. Bucky LP, Percec I. The science of autologous fat grafting: views on current and future approaches to neoadipogenesis. Aesthet Surg J. 2008 May-Jun;28(3):313-21; quiz 322-4. doi: 10.1016/j.asj.2008.02.004. Review. PubMed  PMID: 19083543.
2. Hsu VM, Stransky CA, Bucky LP, Percec I. Fat grafting's past, present, and future: why adipose tissue is emerging as a critical link to the advancement of regenerative medicine. Aesthet Surg J. 2012 Sep;32(7):892-9. doi: 10.1177/1090820X12455658. Review. PubMed PMID: 22942117.
3. Stransky CA, Hsu VM, Dierov R, Hoover WJ, Donahue G, Bucky LP, Percec I. Beyond fat grafting: what adipose tissue can teach us about the molecular mechanisms of human aging. Ann Plast Surg. 2012 Oct;69(4):489-92. doi: 10.1097/SAP.0b013e31824c0e43. PubMed PMID: 22964682.
4. Imadojemu S, Sarwer DB, Percec I, Sonnad SS, Goldsack JE, Berman M, Sobanko JF. Influence of surgical and minimally invasive facial cosmetic procedures on psychosocial outcomes: a systematic review. JAMA Dermatol. 2013 Nov;149(11):1325-33. doi: 10.1001/jamadermatol.2013.6812. Review. PubMed PMID: 24068036.
5. Hsu VM, Wes AM, Tahiri Y, Cornman-Homonoff J, Percec I. Quantified Facial Soft-tissue Strain in Animation Measured by Real-time Dynamic 3-Dimensional Imaging. Plast Reconstr Surg Glob Open. 2014 Oct 7;2(9):e211. doi: 10.1097/GOX.0000000000000185. eCollection 2014 Sep. PubMed PMID: 25426394; PubMed Central PMCID: PMC4229270.
   
    

Lymphedema surgery

Post-mastectomy lymphedema continues to be a major source of morbidity after breast cancer surgery despite the increasing use of more conservative operative interventions such as sentinel node mapping and breast conservation therapy. Our research at Penn focuses on the microsurgical treatment of lymphedema, the influence of breast reconstruction on primary lymphedema development, and the cost/resource burden of lymphedema on health systems recently. Recent publications have focused on risk stratification for the development lymphedema to inform cost-effective resource allocation and tailor perioperative clinical decision-making and counseling based upon individual risk. Future efforts may focus on developing a risk-assessment tool prior to any surgical intervention that can help guide the implementation of proactive instead of reactive management strategies. We also continue to advance the surgical treatment of lymphedema with one of the largest cohorts of women treated with supraclavicular lymph node transfer in the country.

Selected publications

1. Basta MN, Gao L, Wu L.  Operative Treatment of Lymphedema: A systematic meta-analysis of the safety and efficacy of lymphovenous shunt vs. lymphatic tissue transplant. Plast Reconstr Surg. 2014 Apr;133(4):905-13.
2. Basta MN, Gao L, Wu L.  Reply: Operative Treatment of Lymphedema: A systematic meta-analysis of the safety and efficacy of lymphovenous shunt vs. lymphatic tissue transplant. Plastic & Reconstructive Surgery. 2014; (134) 3: 492e-493e.
3. Basta MN, Fischer JP, Kanchwala SK, Silvestre J, Wu LC, Serletti JM, Tchou JC, Fosnot J. A Propensity-Matched Analysis of the Influence of Breast Reconstruction on Subsequent Development of Lymphedema. Plast Reconstr Surg. Accepted, in production.
4. Basta MN, Fox JP, Fosnot J, Serletti JM, Kanchwala SK, Fischer JP. “Women Who Develop Complicated Lymphedema Following Surgical Treatment For Breast Cancer Experience High Rates Of Hospitalization”  Submitted for publication.
5. Pannucci C, Gerety P, Basta M, Wang AR, Mies C, Zhang P, Kanchwala SK. Vascularized Lymph Node Transfer for Lymphedema: Anatomic Comparison of the Supraclavicular and Thoracodorsal Lymph Node Flaps. Journal of Vascular Surgery: Venous and Lymphatic Disorders. 2015; (3) 1: 124.
6. Fosnot J, Fischer JP, Wu LC, Serletti JM. The Patient's Perspective on the Effect of Autologous Breast Reconstruction on Lymphedema. Ann Plast Surg. 2014 Mar 29. [Epub ahead of print] PubMed PMID: 24691304.

Lower extremity reconstruction

Penn Plastics manages some of the most complicated patients in lower extremity reconstruction. Our research endeavors reflect the complicated nature of these clinical efforts. Recent projects have focused on predictors of limb and joint salvage, as well novel, protocol-driven management of complicated lower extremity trauma. We pair closely with our orthopedic colleagues in the management and investigation of these wounds. We have also newly established a multi-institutional database to facilitate cross-institution collaboration and augment the power and applicability of our conclusions.

Selected publications

1. The Versatility of the Anterolateral Thigh Free Flap in Lower Extremity Limb Salvage for Trauma.  Christopher Bibbo, John P. Fischer, Jonas A. Nelson, Liza C.Wu, David Low, Samir Mehta, and Stephen J. Kovach. Accepted-in production,  J Ortho Trauma, 2015, accepted-in production, manuscript# JOT5752
2. Maintaining levels of lower extremity amputation. JSOA-2014-309 Christopher Bibbo DO, David Ehrlich MD, L. Scott Levin MD, Stephen J. Kovach MD. J Orthopaedic Surgical Advances, accepted, January 2015
3. A Lower Extremity Musculoskeletal and Vascular Trauma Protocol in a Children's Hospital May Improve Treatment Response Times and Appropriate Microvascular Coverage. John Flynn, Itai Gans, Keith Baldwin, Michael Nance, Benjamin Chang, Stephen J. Kovach, L Scott Levin. Accepted-in production, J Ortho Trauma, July 2014, JOT6127R
4. Low wound complication rates for the lateral extensile approach for calcaneal ORIF when the lateral calcaneal artery is patent.  Stephen J. Kovach MD, Christopher Bibbo, MD. Foot and Ankle International, manuscript FAI-14-0025-R1. Accepted, 2014
5. Approaching lower extremity reconstruction in the obese population: Does weight matter?  Emily Cleveland BA , John P Fischer, MD, Jonas A Nelson, M.D.,  Jason D Wink, B.A, L. Scott Levin, MD,  Stephen J Kovach, M.D. J Recon Microsurgery, 30(1) p. 263-270 May 2014.
6. Microsurgery without the anastomosis: a review of propeller flaps for distal lower extremity soft tissue reconstruction. Nelson, JA Fischer, JP, Kovach, SJ, Rosson, GD, and Rad, AN. Accepted to Microsurgery, 2013.
7. Cho EH, Garcia RM, Pien I, Kuchibhatla M, Levinson H, Erdmann D, Levin LS, Hollenbeck ST:  Vascular Considerations in Foot and Ankle Free Tissue Transfer: Analysis of 231 Free Flaps. Microsurgery, 2015.
8. Zheng HP, Zhuang YH, Lin J, Zhang YX, Levin LS, Grassetti L, Lazzeri D, Persichetti P. Revisit of the anatomy of the distal perforator of the descending genicular artery and clinical application of its perforator "propeller" flap in the reconstruction of soft tissue defects around the knee. Microsurgery, October 2014.
9. Clement, R. C., Kheir, M. M., Derman, P. B., Flynn, D. N., Speck, R. M., Levin, S., Fleisher, L.:  What are the economic consequences of unplanned readmissions following total knee arthroplasty? Clinical Orthopaedics and Related Research. 472(10):3134-3141. October 2014.
10. Courtney PM, Melnic CM, Gutsche J, Hume EL, Scott LS, Lee GC:  Prospective Evaluation of the Need for Critical Care Intervention after Total Joint Arthroplasty.  Journal of the American College of Surgeons, Vol 219, Number 3, September 2014.
11. Bibbo C, Ehrlich DA, Nguyen HML, Levin LS, Kovach SJ:  Low Wound Complication Rates for the Lateral Extensile Approach for Calcaneal ORIF When the Lateral Calcaneal Artery is Patent.  Foot and Ankle International, 35(7):650-656. July 2014.
12. Cho EH, Garcia R, Pien I, Thomas S, Levin LS, Hollenbeck ST:  An Algorithmic Approach for Managing Orthopaedic Surgical Wounds of the Foot and Ankle. Clinical Orthopaedics and Related Research, Vol. 473, No. 6, pgs. 1991-1929. June 2014.
13. Haddock NT, Wapner K, Levin LS:  Vascular Bone Transfer Options in the Foot and Ankle: A Retrospective Review and Update on Strategies.  Journal of Plastic and Reconstructive Surgery, Vol. 132, No. 3, pgs. 685-693. September 2013.
14. Fischer J, Nelson J, Kovach S, Levin LS, Wu L, Cleveland E, Serletti J:  A Retrospective Review of Outcomes and flap Selection in Free Tissue Transfers for Complex Lower Extremity Reconstruction.  Journal of Reconstructive Microsurgery, Vol. 29(6):407-416.  July 2013.
15. Tintle SM, Kovach SJ, Levin LS:  Free Tissue Transfer to the Foot and Ankle:  Perforator Flaps.  Techniques in Foot and Ankle Surgery, Vol. 12, No. 2, pgs. 79-86, June, 2013.

Evgeniy B. Eruslanov, PhD

Description of Research Expertise

Evgeniy B. Eruslanov, PhD. According to numerous mouse studies, the protumoral and immunosuppressive role of Tumor-Associated Myeloid Cells in cancer is a dominating concept. However, the characterization of tumor microenvironment in cancer patients is still in its infancy and the functional crosstalk between immune and tumor cells in human remains unexplored. My research interests are directed toward understanding the specific functional and regulatory roles of distinct subsets of tumor-infiltrating neutrophils and macrophages in patients with lung cancer.

Selected Publications

Eruslanov E, Nefedova Y, and Gabrilovich D. : The heterogeneity of neutrophils in cancer and its implication for therapeutic targeting. Nature Immunology 1(26): 17-28, Jan 2025.

Sunil Singhal, Abhishek S. Rao, Jason Stadanlick, Kyle Bruns, Neil T. Sullivan, Andres Bermudez, Adam Honig-Frand, Ryan Krouse, Sachinthani Arambepola, Emily Guo, Edmund K. Moon, George Georgiou, Tomas Valerius, Steven M. Albelda, and Evgeniy B. Eruslanov: Human tumor-associated macrophages and neutrophils regulate anti-tumor antibody efficacy through lethal and sublethal trogocytosis. Cancer Research 7(84): 1029-1047, January 2024.

3. Quail DF, Amulic B, Aziz M, Barnes BJ, Eruslanov E, Fridlender ZG, Goodridge HS, Granot Z, Hidalgo A, Huttenlocher A, Kaplan MJ, Malanchi I, Merghoub T, Meylan E, Mittal V, Pittet MJ, Rubio-Ponce A, Udalova IA, van den Berg TK, Wagner DD, Wang P, Zychlinsky A, de Visser KE, Egeblad M, Kubes P.J : Neutrophil phenotypes and functions in cancer: A consensus statement. J. Exp Med. (6;219 (6) ), June 2022.

Sunil Singhal, MD

The Thoracic Surgery Research Laboratory, directed by Sunil Singhal, MD, is dedicated to the mission of curing patients with diseases of the chest, with a strong interest in lung cancer. According to a report by the CDC in 2006, lung cancer is the number one cause of cancer death in the United States, responsible for more deaths than breast, colon, prostate, and pancreatic cancers combined. Overall, it is the number two killer worldwide just behind heart disease. Our focus is to improve more than just outcomes, but the quality of life in patients with lung, esophageal and mesothelial cancers. We strive to combine the latest in technological surgical innovations with an expanding foundational understanding of oncogenesis and immunology.

Visit the Thoracic Surgery Research Laboratory website.

Peter L. Abt, MD

Peter L. Abt, MD research activities involve both outcomes and translational research. We have collaborations with multiple investigators from a variety of institutions.

Donation after cardiac death organ donation

1. Understanding how donor hemodynamic profiles impact graft and recipient survival
2. Retransplantation in liver recipients
3. DCD liver transplant consortium for retrospective and prospective studies

Renal dysfunction and failure after liver transplantation

There are several ongoing studies which seek to characterize the link between liver disease and kidney dysfunction.

1. Multicenter NIH funded study examining markers of renal injury
2. Development of models to predict chronic kidney injury in liver recipients who experience acute kidney injury
3. Validation of models to predict end stage renal disease after liver transplant

Matthew H. Levine, MD, PhD

In his current laboratory, Matthew H. Levine, MD, PhD has several projects under active investigation pertaining to the role of regulatory T cells (Treg) in transplantation tolerance induction. This work is being done in collaboration with Dr. Wayne Hancock at the Children’s Hospital of Philadelphia. The first of these investigations involves the study of chromatin conformational regulation by histone acetylation/deacetylation and how this impacts the number and function of Treg in murine transplantation models. It is becoming apparent that inhibitors of histone deacetylases (HDACs) can improve both the number and the function of Tregs and that this can induce tolerance to MHC-mismatched transplants in mice with reduced or no conventional immunosuppression. The overall aim of this work is to provide understanding of the role that Tregs play in transplant tolerance and to dissect pathways in Treg induction that may be clinically relevant for drug targeting in animal models and eventually in humans.

A second, more clinically-directed, area of active interest is in the impact that conventional immunosuppression has on the numbers and function of Treg in human transplant recipients. We are studying the Treg profile in liver transplant recipients as immunosuppression utilization is diminished during the first year after transplantation. This should give some information about what impact conventional immunosuppression such as calcinuerin inhibitors have on the function of Treg. This information could impact the strategy of immunosuppressive management in transplant recipients.

Additionally, we are investigating the role that HDACs and heat shock proteins (hsps) play in the tolerance of and recovery from ischemia-reperfusion injury in a murine model. This model utilizes unilateral murine renal ischemia and recovery to investigate the impact the HDAC inhibition, through small molecules and knockouts, has on end organ function and survival. Heat shock proteins are known to play a role in ischemia-reperfusion tolerance but the interaction between HDACs, chromatin conformational modification, gene expression, and heat shock proteins is not well-understood and this is an area that is under active investigation at this time. This work has the potential to impact such diverse areas of clinical medicine as organ preservation, vascular ischemic injury such as myocardial infarction and stroke, and tolerance of ischemia in acute vascular insufficiency or during vascular surgery.

Lastly, Dr. Levine has active ongoing clinical research that includes a detailed analysis of liver transplantation for hepatocellular carcinoma, outcomes in particular subgroups of living and deceased donor renal transplant recipients and donors, and factors associated with favorable and unfavorable outcomes in renal transplantation.

Ali Naji, MD, PhD

Learn more about Ali Naji, MD, PhD research projects.

Human Pancreas and Analysis Program (HPPAP) (UC4)
9/20/2016 - 09/19/2020

The Human Pancreas Analysis Program (HPAP) consortium brings together investigators with expertise in pancreas procurement and islet isolation, immunology, genomics, epigenomics and islet bioenergetics to study cells and tissues relevant to beta cell loss of type 1 diabetes mellitus.  The HPAP group will make the vast data accumulated available through the highly open-access resource database (PANC DB), an online database that will be developed throughout the project.  The extensive and high-quality datasets will be made available to the diabetes research community-at-large for further discovery.  
Role:  PI

Project 2:  Complement in Inflammatory Diseases: Mechanisms & Therapeutic Modulation
06/01/14 - 05/31/19

The program project employs the highly integrated and holistic approach to describe common and distinct denominators of complement involvement in inflammatory conditions and open avenues for improved therapeutic strategies. The goal of Project 2 is to delineate the mechanisms responsible for complement activation and the role of complement in the outcome of kidney transplantation.
Role: Co-Investigator

Targeting BLyS/BAFF in Non-Human Primate
08/01/12 - 07/31/2018

The goal of the application is to assess the efficacy of Blys/BAFF neutralization to promote B lymphocyte compartment tolerance in non-human primate recipients of islet allografts.
Role: PI

Integrated Islet Distribution Program
07/02/14 - 06/30/2018

The major goal of this Islet Cell Resource (ICR) application is the isolation, quality assessment and distribution of human pancreatic islets for transplantation into patients with type I insulin-dependent diabetes mellitus and for basic research in diabetes.
Role: PI

Completed research support

B-Lymphocyte Immunotherapy in Islet Transplantation
09/01/04 - 07/31/17

The major goal of this clinical islet transplantation (CIT) program is implementation of a novel induction immunotherapy targeting T lymphocyte compartment to promote islet allograft survival in 2 patient cohorts 1) islet transplantation in subjects with type 1 diabetes mellitus complicated by hypoglycemic unawareness, islet alone (IA); and 2) islet transplantation in diabetic subjects with previous renal transplant, islet after kidney (IAK).

Immunosuppression with Antithymocyte Globulin, Rituximab, Tacrolimus and Sirolimus, Followed by Withdrawal of Tacrolimus and Sirolimus, in Living Donor Renal Transplant Recipients
05/01/10 - 05/01/17

The goal of this clinical trial is to assess the efficacy of a combined B and T cell immunotherapy for induction of renal transplant tolerance
Role: Site PI at Penn

Biomarkers of progression in the at risk setting for type 1 diabetes
12/01/14 – 11/30/15

We studied serum samples from at risk subjects enrolled in TrialNet, which provided stage dependent samples ideal for characterizing and profiling beta cell specific exosomes.
Role: Co-PI

Epigenomic Profiling of Normal and Diabetic Pancreatic Beta Cells
07/01/09 – 06/30/14

The major goal of this program is to produce a high-resolution map of epigenetic marks of human beta cells from normal controls and type 2 diabetic patients.
Role: Co-Investigator

Kim M. Olthoff, MD

Kim M. Olthoff, MD research involves both human translational studies and clinical research in the field of liver transplantation and regeneration and addressing disparities in organ transplantation. Her translational research is focused on liver recovery in the transplant setting, exploring the molecular aspects and -omics of liver regeneration, graft dysfunction, ischemic injury, and immunity in the transplant setting, and the clinical manifestations of genetic transfer with the graft. Her clinical research focuses on organ allocation, living liver donation, patient outcomes, and minimizing disparities in organ allocation and access to transplant.

These lines of investigation are funded by NIH grants, private industry, and the Biesecker Center for Pediatric Liver Disease. The Penn Transplant Institute research personnel have published in top-ranked journals such as Nature Medicine, Hepatology, American Journal of Transplantation, Liver Transplantation and Transplantation.

Human translational studies

1. The Biorepository of the Transplant Institute at Penn (BioTIP). Dr. Olthoff is the PI for this large biorepository of blood, serum, and tissue samples from transplant recipient's and living donors. The repository serves as a valuable resource for numerous collaborations and ancillary studies.
2. Liver regeneration and function in the transplant Setting. Assessment of liver growth and function in donors and recipients following partial hepatectomy, living donor transplantation, and deceased donor transplantation using genomics, proteomics, and metabolomics.
3. Use of cfDNA as a biomarker for liver regeneration and recovery. Whole genome sequencing (WGS)-based technology for the detection liver regeneration or injury.
4. Use of polygenic risk scores to predict the development of metabolic syndrome following liver transplantation. Integration of genomic data from transplant biorepositories that will be utilized to construct polygenic risk models specific to transplantation.

Clinical research

1. Clinical variables that impact liver regeneration after living donation and transplantation
2. Long-term outcomes following living liver donation
3. Assessing the prevalence of risk factors for metabolic syndrome and cardiovascular complications in liver transplant recipients, comparing recipients of deceased donors (DDLT) to those of living donors (LDLT).
4. Variables impacting Early Allograft Dysfunction (EAD) and effect on post-transplant survival. Effect of ex vivo machine perfusion on incidence of EAD
5. The impact of Donor Care Units on increasing organ utilization
6. Outcomes following combined heart-liver transplant

Selected list of Dr. Olthoff's published work.

Division research

The Division of Traumatology, Surgical Critical Care, and Emergency Surgery is committed to generating knowledge to improve the care of ill and injured patients in our own community and around the world. Our faculty and research teams conduct, implement, and disseminate innovative, meaningful research across basic science, translational, clinical, and health services research.

Visit the Research in Traumatology, Surgical Critical Care, and Emergency Surgery website.

Penn acute research collaboration (PARC)

Penn Acute Research Collaboration: Establishing Cross-Disciplinary Translational Investigation at Penn Medicine
Founded in 2016, PARC is an initiative for interdepartmental translational research at Penn Presbyterian Medical Center, bringing together Penn investigators from wide range of disciplines that will now interact in more meaningful and innovative collaborations.

Visit the Penn Acute Research Collaboration (PARC) website.

Penn injury science center

We bring together university, community, and government partners around injury prevention and intervention programs with the greatest potential for impact. We promote and perform action-oriented research, training, and outreach to reduce injuries, violence, and their impact on people in Philadelphia and around the world.

Focus Areas

Our scholars study and practice across many focus areas to prevent injury on multiple levels: “stop it” from happening in the first place, “fix it” once it has happened, and “live on” by minimizing long-term impacts and risk of re-injury.

Visit the Penn Injury Science Center website.

Scott M. Damrauer, MD

Scott M. Damrauer, MD research utilizes genomic, proteomic, and metabolomic approaches to characterize the biological pathways and cellular mechanisms that are most relevant in the etiology, progression, and treatment of heart and vascular disease. He is a clinically active vascular surgeon at the Corporal Michael J. Crescenz VA (CMCVA) who treats Veterans with vascular disease on a daily basis, and he capitalizes on this in his research program as he leverage the techniques of molecular and genetic epidemiology to understand basic pathophysiology.

Dr. Damrauer's research group is working with investigators at the CMCVA, the VA Palo Alto Healthcare System, the VA Boston Healthcare System, and the Atlanta VA Medical Center, to lead the effort to understand the genetic basis of complex cardio-metabolic traits in the VA Million Veteran Program. Specifically, they are using both discovery-based and hypothesis-driven approaches to understand the genetics of peripheral artery disease (PAD), abdominal aortic aneurysm (AAA), and venous thromboembolism (VTE). In addition, they have ongoing related cardio-metabolic and PAD genetics projects utilizing a number of other large population-based cohorts, including the UK Biobank, PennMedicine BioBank, and the Pakistan Risk of Myocardial Infarction Study.

Grace J. Wang, MD, MSCE

Grace J. Wang, MD, MSCE is an Associate Professor of Surgery in the Division of Vascular and Endovascular Surgery at the Hospital of the University of Pennsylvania.  She completed her general surgical training at the Massachusetts General Hospital, an affiliate of Harvard Medical School.  She then completed a Vascular and Endovascular fellowship at the Hospital of the University of Pennsylvania, whereupon she stayed on as faculty.

Her clinical interests include carotid endarterectomy and carotid stenting, endovascular and open interventions for limb salvage, endovascular repair of thoracic and abdominal aortic aneurysms, and dialysis access. Dr. Wang is also Clinical Director of the Vascular Lab at the Hospital of the University of Pennsylvania.

She completed a Masters of Science in Clinical Epidemiology through the Center for Clinical Epidemiology and Biostatistics at University of Pennsylvania. The degree has given her the ability to analyze large datasets and create predictive models to understand poor outcomes in vascular surgical patients.  Her research interests lie in using large scale databases to study trends in practice, predictors of outcomes, and gender disparities in access to care in vascular surgery. She has utilized the Nationwide Inpatient Sample (NIS), National Surgical Quality Improvement (NSQIP) as well as the Vascular Quality Initiative (VQI) registries to conduct these studies.  She has a focused research interest on the application of thoracic endovascular aortic repair (TEVAR) to thoracic aortic pathologies. She has published extensively on TEVAR: 3 book chapters and 18 manuscripts including peer reviewed and non-peer-reviewed publications.

As the VQI is a large data respository of most vascular surgical procedures, she continues to publish manuscripts which span the interventions and surgical procedures that are performed by vascular surgeons including carotid endarterectomy, carotid stenting, IVC filter placement, lower extremity bypass, and others.

Notable publications:

1. Wang GJ, Jackson BM, Foley PJ, Damrauer SM, Goodney PP, Kelz RR, Wirtalla C, Fairman RM: National trends in admissions, repair and mortality for thoracic aortic aneurysm and type B dissection in the National Inpatient Sample (NIS). Journal of Vascular Surgery 2018 Notes: accepted for publication.
2. Wang GJ, Cambria RP, Lombardi JV, Azizzadeh A, White RA, Abel DB,Cronenwett JL, Beck AW. Thirty-Day Outcomes from The Society for Vascular Surgery Vascular Quality Initiative (SVS VQI) TEVAR for Type B Dissection Project. Journal of Vascular Surgery. Accepted for publication.
3. Wang GJ, Jackson BM, Foley PJ, Damrauer SM, Kalapatapu V, Golden MA, Fairman RM: Treating peripheral artery disease in the wake of rising costs and protracted length of stay. Annals of Vascular Surgery 44: 253-260, Oct. 2017 Notes: Epub May 4, 2017.

Vascular laboratory

The Vascular Laboratory is an Intersocietal Commission for the Accreditation of Vascular Laboratories (ICAVL) accredited facility that serves both inpatients and outpatients in our state of the art equipped sites. The laboratory is staffed by highly qualified technologists who are certified Registered Vascular Technologists (RVT) with credentials from the American Registry of Diagnostic Medical Sonography. The laboratory staff performs over 12,000 tests per year. The laboratory performs testing utilizing ICAVL approved protocols and participates in testing for clinical trials.

• Grace J. Wang, MD, MSCE
• Scott M. Damrauer, MD

Our mission statement

The mission of the Vascular Laboratory at the Hospital of the University of Pennsylvania is to aid in the diagnosis and treatment of peripheral vascular disease through: 

Technical director

• Adam S. Olsen, BS, RVT

Technical staff

• Joseph Fleckenstein, BS, RVT
• Allison Gordon BS, RVT
• Abby Gerding BS, RCDS, RVT
• Jayshree Mahida, BS, RCDS, RVT
• Eileen R. Mathers, RVT
• Courtney Sheehan, BS, RVT

Per-diem technical staff

• Melanie Efelis BS, RVT
• Christopher Petoskey BS, RVT
• Monsurat Aminu BS, RVT
• Julia T. Davis MS, RN, RVT

Support staff

• Tonya Daniels, Patient Services Associate
• John Delhomme, Clinical Services Associate

Tests performed

Arterial physiological testing

• Lower Extremity Pulse Volume Recordings and Segmental Pressures including Ankle-Brachial Index and Toe-Brachial Index
• Upper Extremity Pulse Volume Recordings and Segmental Pressures
• Digital Photoplethysmography and Pressures

Arterial color flow duplex ultrasonography

• Arterial Duplex Ultrasonography Evaluation of Bypass Grafts
• Arterial Duplex Ultrasonography of Lower and Upper Extremity Arteries
• Evaluation for Pseudoaneurysm and Ultrasound Guided Thrombin Injections performed by an attending Vascular Surgeon
• Radial artery Mapping prior to Coronary Artery Bypass
• Evaluation of dialysis access fistula and grafts

Carotid artery color flow duplex ultrasonography

• Evaluation of Carotid Arteries, Vertebral Arteries and Subclavian Arteries
• Carotid Intima-Medial Thickening Evaluations (self-pay)

Venous color flow duplex ultrasonography

• Venous Duplex evaluation for Deep Vein Thrombosis  of upper and lower extremities
• Venous Duplex evaluation for venous insufficiency
• Pre-operative vein mapping prior to bypass surgery and dialysis access placement

Abdominal/visceral duplex ultrasonography

• Abdominal Aortic Aneurysm and evaluation of aortic stent grafts
• Renal Artery Duplex
• Evaluation of Liver Transplant
• Mesenteric Duplex

Locations

Inpatient ab
Hospital of the University of Pennsylvania
3400 Spruce Street, 6 Dulles
Philadelphia, PA 19104

Outpatient lab
Perelman Center for Advanced Medicine
Heart and Vascular Testing
3400 Civic Center Boulevard, Ground Floor East Pavilion
Philadelphia, PA 19104
Phone: 215-662-2084; prompt 1 for inpatient requests
prompt 2 for outpatient requests
Fax: 215-349-8555 or 215-615-8558
Hours of operation: 7:30 AM- 5:00 PM, Monday through Friday