Research programs
A longstanding focus of this group has been oxidant injury and ischemia/reperfusion injury, while more recent work has established clinical and genetic risk factors for ARDS, identifying novel endotypes of the syndrome, and examining the role of neutrophils, red blood cells, glycans, and proteins in the development of lung injury. Translational research within the group is enhanced by collaborations with large sepsis, trauma, and transplant cohorts of critically ill patients.
The group has a strong interest in emerging therapeutics and the potential for precision medicine. Key collaborations have been established with Dr. Vladimir Muzykantov from the Center for Targeted Therapeutics and Translational Nanomedicine, Drs. Dan Huh and Susan Margulies of the Department of Bioengineering, Dr. Ed Morrissey of Developmental Biology, and Dr. Scott Worthen from the Department of Neonatology. Within the Division, Drs. Christofidou-Solomidou, Mangalmurti, and DeLisser lead the bench research of lung injury while Drs. Christie, Meyer, Shashaty, and Reilly coordinate the clinical and translational ARDS research.
Specific faculty interests include:
- Jason Christie, MD, MSCE
- Molecular Epidemiology of Acute Lung Injury
- Role of Oxidants in Development of ARDS
- Outcomes after ARDS
- Horace DeLisser, MD
- Role of PECAM-1 in angiogenesis and tumor cell metastasis
- Role of hyaluronan receptors (RHAMM and CD44) in angiogenesis
- Role of cell adhesion molecules in post-natal lung development
- Nilam Mangalmurti, MD
- Role of endothelial innate immune receptors in lung injury
- Role of cell adhesion molecules in post-natal lung development
- Role of regulated necrosis in the development of lung injury
- Nuala Meyer, MD
- Genetic risk factors for ARDS
- Functional genomics of lung injury
- Molecular epidemiology of severe sepsis in the ICU (MESSI cohort study)
- Identification of sepsis and ARDS endotypes for precision therapy
- Vladimir Muzykantov, MD, PhD [Pharmacology]
- Lung drug delivery using nanoparticles
- Intracellular delivery of antioxidants in the pulmonary endothelium
- Targeting drugs to endothelial cells
- Vascular drug delivery using blood cells as carriers
- John Reilly, MD
- Blood group as a molecular risk factor for ARDS
- Role of Glycobiology in ARDS pathogenesis and outcome
- Michael Shashaty, MD
- Clinical and molecular risk factors for acute kidney failure in critically ill patients
- Impact of obesity on organ failure during critical illness
The Center is led by Jason Christie, MD, MSCE. The CTLB works with the PCBC to provide key resources to SOM/University-wide researchers and trainees to vertically integrate basic and clinical science research through non-overlapping translational core functions focused on advanced lung diseases, lung transplantation, and critical illness syndromes.
This includes:
- Biosample Acquisition and Clinical Data Management Core
- A Molecular Biology and Measurement Core
- A Lung Disease Modeling Core
- A vibrant seminar series including extramural speakers, partnered with other centers outreach, with a focus on interacting closely with existing Departments, Centers, and Institutes to support lung disease research, especially in immunology (IFI), environmental lung diseases (CEET), epidemiology (CCEB), pediatric and neonatal lung disease (CHOP), Orphan Diseases, pulmonary vascular disease (CVI), lung transplantation (Dept. of Surgery), experimental therapies (ITMAT), and lung cancer (ACC).
Edward Morrisey, PhD lab also has a strong focus on the development and regeneration of the cardiovascular system. His ultimate goal is to better understand how signaling and epigenetic pathways, regulate development and regeneration of the lungs and heart, leading to the development of new therapeutic approaches for lung and cardiac diseases.
Specific Projects include:
- How Wnt signaling, non-coding RNAs, forkhead transcription factors, and epigenetic mechanisms regulate pulmonary and cardiovascular development
- Defining how the pulmonary and cardiovascular systems co-develop i.e. How do the pulmonary vessels form?
- Determine how developmental pathways reactivated in the adult lung and whether they are critical to the repair and regeneration after injury or in disease states.
Michael Beers, MD heads this program. The bench science program includes characterization of the biosynthetic pathways for surfactant system components, the role of cellular quality control pathways in the pathogenesis of parenchymal lung disease, and the function of surfactant in immunity and inflammation. Other members of the bench research group include Dr. Surafel Mulugeta and Dr. Arie Hawkins. In collaboration with the Center for Translational Lung Biology, a translational program in Interstitial Lung Disease has been developed which utilizes a patient data base, biospecimens, and lung explants for proof of concept studies and investigator-initiated questions. The program is funded by Veterans Administration Merit Review, an RO1 grant, and the Pulmonary Fibrosis Foundation.
Specific Projects include:
- Characterization of The Biosynthesis of Surfactant Protein C
- Protein Synthesis and Quality Control In the Lung Epithelium (UPR, ERAD, autophagy)
- Using SP-C and ABCA3 mutations to understand the pathogenesis of fibrotic lung diseases (Adult IPF patients and transgenic mouse models)
- Questions in Alveolar Epithelial Cell Biology (Lamellar Body genesis; endocytosis; regulated secretion)
- Lung Collectins and Host Defense
- Lung Collectins and Inflammation (Bleomycin, hyperoxia)
The Interstitial Lung Disease program, which has adopted a team science approach, leverages a large patient cohort, active wet-bench laboratory support, a dedicated research coordinator/technical staff, and collaborative faculty to conduct a wide variety of ILD related investigations. Maryl Kreider, MD, MSCE, Director of the ILD clinical program serves as lead clinical investigator. Greg Tino, MD, Milt Rossman, MD and Mary Porteous, MD conduct a variety of industry sponsored translational and clinical trials in IPF, lung-related collagen vascular diseases, and sarcoidosis that explore natural history, pathogenesis, and new drug therapies. Michael Beers, MD serves as Scientific Director for the program and provides biobanking and lab support as well as conducts preclinical ILD studies. The program has been an active site for IPFnet sponsored research and is also recognized as a Center of Excellence by the Pulmonary Fibrosis Foundation (PFF), participating in PFF-initiated projects including development of a national pulmonary fibrosis registry.
Specific clinical projects include:
- Epidemiology and Identification of risk factors for the development of Interstitial Lung Diseases including aging (ILD Group)
- Drug trials with novel agents for the treatment of ILD and sarcoidosis (Drs. Kreider, Tino, and Rossman)
- Development of a clinical and biological sample repository (Drs. Kreider, Beers, and Porteous with the Center for Translational Lung Biology)
Specific translational and pre-clinical projects include:
- Role of T regulatory T cells in Sarcoidosis (Dr. Wayne Hancock (Pathology))
- Preclinical studies using novel mouse models of ILD (Dr. Beers)
- Translational studies using isolated primary lung epithelial and mesenchymal cells (Dr Beers with the Pulmonary Center for Lung Biology)
Ronald Collman, MD from Pulmonary runs a program investigating microbial pathogenesis in the respiratory tract, including: (a) basic mechanisms in HIV-1 biology that contribute to AIDS pathogenesis and (b) application of molecular microbiome tools to the respiratory tract and diseases in pulmonary and critical care medicine. Much of his recent research has focused on the pulmonary microbiome including changes seen in HIV infection, lung transplantation, sarcoidosis and critical illness/acute lung injury. He interacts closely with colleagues in Pulmonary (Drs. Christie, Diamond, Haas) as well as Microbiology, Infectious Disease, and Hematology. Support for this research includes NIH R01 and U01 grants. Dr. Collman is also Co-Director of the Penn Center for AIDS Research.
Specific projects include:
- Metagenomic analysis of the Respiratory Tract Microbiome in health and disease
- Mechanisms of HIV-1 entry into target cells, target tropism and pathogenesis, and molecular virology
The Penn Center for Pulmonary Biology (PCPB) is housed on the second floor of the newly renovated Stemmler Building and occupies 12,500 square feet of space including some of the most advanced research facilities at Penn. The PCPB is directed by Dr. Edward Morrisey and serves as an institution-wide locus to foster and integrate collaboration of basic lung biology faculty members and trainees across disciplines, schools, and departments at Penn.
The PCPB brings together a diverse group of investigators and clinicians with the goal of unraveling the underlying mechanisms of respiratory disease and begin to utilize such findings to improve clinical medicine.
The primary goals of the PCPB are:
- Create resources at Penn and CHOP to facilitate basic discovery through translational research in pulmonary biology with a focus on using humans as a “model system”.
- Bring together researchers directly involved in pulmonary research, as well as those outside the field to build an interactive and rigorous community capable of addressing the most compelling and important questions in pulmonary biology.
- Educate and train the next generation of scientists and physician-scientists who are critical for the future success of pulmonary research.
There are both epidemiological and bench projects active.
Specific faculty research interests include:
- Steven Kawut, MD, MS
- The risk factors and outcomes of pulmonary arterial hypertension and other forms of pulmonary vascular disease, such as hepatopulmonary syndrome
- Studying right ventricular function in patients with pulmonary arterial hypertension as well as disease-free individuals in population-based epidemiologic studies
- Clinical trials of novel agents for pulmonary vascular disease
- Horace DeLisser, MD
- Isolation and characterization of pulmonary endothelial and smooth muscle cells from pulmonary hypertension patients
Faculty members in Penn Medicine's pulmonary division, led by Steven Albelda, MD, interact closely with faculty from thoracic surgery, oncology and pathology.
Other members of the group include Drs. Anil Vachani, Andrew Haas, Edmund Moon from Pulmonary, Drs. Sunil Singhal and Evgeniy Eruslavnov from Thoracic Surgery, Dr. Corey Langer from Oncology, and Drs. Leslie Litzky and Charu Desponde from pathology. Research from this group is supported by NCI-funded Program Projects, a NIEHS Superfund Grant, NIH RO1 and KO8 grants, Industry, and Foundation support. The Abramson Cancer Center supports a Translational Center of Excellence in Lung Cancer Immunobiology and Immunotherapy.
Members of the group and their research interests include:
- Steve Albelda, MD
- Preclinical studies of immunogene therapy for lung cancer and mesothelioma
- Immune analysis of clinical trials using gene therapy or immunotherapy
- Understanding the lung cancer tumor microenvironment
- Precision Medicine
- Optimizing adoptive T cell transfer for the treatment of thoracic malignancies
- Andrew Haas, MD, PhD
- Clinical trials using gene therapy or immunotherapy to treat malignant mesothelioma and lung cancer
- Interventional bronchoscopy treatment of COPD
- Sunil Singhal, MD / Evgeniy Eruslanov, PhD
- Intraoperative imaging to detect residual or recurrent cancer
- Lung cancer microenvironment with a focus on myeloid cells
- Anil Vachani, MD
- Determination of markers to predict survival after lung cancer surgery
- Discovery of biomarkers for early detection of lung cancer
- Gene environment interactions in lung cancer
- Precision Medicine
More than 50 lung transplants are performed at Penn every year. Penn is the coordinating site for the Lung Transplant Outcomes Group Consortium, the multicentered lung transplant cohort study of over 1600 subjects, currently funded by several R01 grants. Faculty conducting research include Drs. Jason Christie, Vivek Ahya, Mary Porteous, and Josh Diamond. Several clinical and translational projects are currently active. These are funded by NIH and Industry grants. A translational Program Project is being planned that will focus on acute graft dysfunction and use the newly developed program in extracorporeal lung perfusion headed by Dr. Edward Cantu of Surgery.
Specific faculty research interests include:
- Jason Christie, MD, MSCE
- Dr. Christie is the founder of the lung transplant outcomes group (LTOG), which is a multicentered cohort study the etiology and pathogenesis of acute lung injury following lung transplantation (termed primary graft dysfunction), with over 2200 subjects enrolled. His research focuses on the role of oxidative stress, coagulation/fibrinolysis, inflammatory and innate immune pathways in primary graft dysfunction. This line of research is funded by several R01 grants from NHLBI, focusing on genetic risks, innate immunity, autoimmunity to lung-specific minor histocompatibility antigens, obesity, regulatory T cell function, and the effects of smoke exposure on donor
- Vladimir Muzykantov, MD, PhD (Pharmacology)
- Targeted drug delivery to the pulmonary vasculature for management of lung I/R