Steven M. Albelda, M.D.

William Maul Measey Professor of Medicine
Vice Chief, Pulmonary, Allergy, and Critical Care Division
Director of Lung Research
Co-Director, Thoracic Oncology Laboratories

The Thoracic Oncology Research Laboratory

Education:

• MD: University of Pennsylvania
• Residency: Hospital of the University of Pennsylvania
• Fellowship: Hospital of the University of Pennsylvania

Dr. Albelda has been a member of the Penn community since 1975 when he enrolled in the Medical School after graduating summa cum laude from Williams College. He was honored by election to AOA in his junior year and graduated with his M.D. in 1979 at the top of his class (winning the Dr. A.O.J. Kelley Prize, the Dr. Spencer Morris Prize, and the Lawrence Saunders Prize).

Dr. Albelda received his post-graduate training at Penn. He is boarded in Internal Medicine, Pulmonary Medicine, and Critical Care Medicine. In addition to continuing his clinical activities, he has also pursued an active basic research career. In 1985, he received a prestigious Physician-Scientist Award from the Lung Division of the National Institutes of Health (NIH) that allowed him to receive additional training at the Wistar Institute, where he holds the title of Adjunct Professor.

Dr. Albelda is the William Maul Measey Professor of Medicine in the Department of Medicine, Associate Director of the Pulmonary Division, Director of Lung Research, and Co-Director of the Thoracic Oncology Laboratories. His clinical interests are primarily in thoracic oncology and his research interests are focused on the molecular mechanisms of inflammation and cell adhesion and on developing novel approaches to the treatment of lung and chest wall cancers.

Dr. Albelda holds grants from the National Institutes of Health and has been an Established Investigator of the American Heart Association. He has published over 140 peer-reviewed papers, along with numerous review articles and book chapters. He has spoken at and chaired numerous national and international meetings. He is an associate editor of the American Journal of Respiratory Cell and Molecular Biology, and is on the editorial board of the journals, American Journal of Physiology (Lung Cell. Mol. Physiol.), and Cancer Gene Therapy, as well as regularly reviewing manuscripts for many scientific journals.

Research Program I
Immuno-gene Therapy for Thoracic Malignancies (with Dan Sterman)

Lung cancer and other thoracic malignancies are the leading cause of cancer deaths in the United States today. The Thoracic Oncology Research Laboratory is focusing on the design of new treatment strategies for lung cancer and mesothelioma based on the rapidly evolving disciplines of molecular biology, immunotherapy, and gene therapy. Multiple tumor models are in place, including a transgenic, orthotopic model of lung cancer based on activation of the Kras oncogene.

A number of areas of research are available. Using a variety of preclinical models of lung cancer and mesothelioma we are exploring ways to stimulate anti-tumor immune responses and to augment these anti-tumor responses using approaches like COX-2 inhibitors, TGFbeta inhibitors, antibodies against B-cells, tumor-macrophage activators, and chemotherapeutic drugs.
A Phase 1 clinical trials for patients with mesothelioma are currently underway. Opportunities are available for translational work analyzing tumor responses and immune endpoints from patient samples collected in the trials.

Fridlender Z.V., Sun, J., Kim, S., Kapoor, V., Cheng, G, Ling, L., Worthen G.S., Albelda, S.M., Polarization of Tumor-Associated Neutrophil (TAN) Phenotype by TGF-b: “N1” versus “N2” TAN,  Cancer Cell, in press.

Wallace, A., Kapoor, V., Sun, J., Mrass, P., Weninger, W., Heitjan, D.F., June, C., Kaiser, L.R., Ling, L.E., Albelda, S.M. TGF-b receptor blockade augments the effectiveness of adoptive T-cell therapy of established solid tumors.  Clin. Cancer Res., 14: 3966-3974, 2008.

Kim, S, Buchlis, G., Fridlender, Z.G., Sun, J., Kapoor, V., Cheng, G, Haas, A., Cheung, H.K., Zhang, X., Corbley, M,  Kaiser, LR, Ling, LE., Albelda, SM.  Systemic Blockade of Transforming Growth Factor-b Signaling Augments the Efficacy of Immunogene Therapy. Cancer Research, 68:10247-10256, 2008.

Sterman, D.H., Recio, A.R., Carroll, R.G., Gillespie, C.T., Haas A., Vachani, A., Kapoor V., Sun, J., Hodinka, R., Brown, J.L., Corble,y M.J., Parr, M., Ho M.,  Pastan I., Machuzak, M., Benedict, W., Zhang, X, Lord, E.M., Litzky, L.A., Heitjan, D.F., June C.H.,  Kaiser L.R., Vonderheide, R.H., and Albelda, S.M. A Phase I Clinical Trial of Single-Dose Intrapleural Interferon-Beta Gene Transfer For Malignant Mesothelioma and Metastatic Pleural Effusions: High Rate of Anti-Tumor Immune Responses, Clinical Cancer Research, 13:4456-4466, 2007.

Suzuki E ,  Kim, S, Cheung, HK, Corbley, M,  Zhang X, Sun, L, Shan F, Singh, J., Lee, WC, Albelda,SM, Ling, LE. A Novel Small Molecule Inhibitor of TGF-beta type I Receptor Kinase (SM16) Inhibits Murine Mesothelioma Tumor Growth  in vivo and Prevents the Extent of Tumor Recurrence After Surgical Resection.  Cancer Research, 67:2351-2359, 2007.

Wilderman, M., Kim,, S., Gillespie, C.T., Sun, J., Kapoor, V., Vachani, A., , Sterman, D., Kaiser, L., Albelda, S.M. Blockade of TNFalpha Decreases Both Inflammation and Efficacy of Intrapulmonary Ad.IFN Beta Immunotherapy in an Orthotopic Model of Bronchogenic Lung Cancer, Molecular Therapy, 13:910-917, 2006.

Haas, A., Sun, J., Vachani, A., Wallace, A.F., Silverberg, M., Kapoor, V., Albelda, S.M.  Cyclooxygenase-2 Inhibition augments efficacy of a cancer vaccine.  Clinical Cancer Research, 12:214-222, 2006

Sterman DH, Recio A, Vachani, A., Sun, J., Cheung, L., DeLong P, Amin KM, Litzky LA, Wilson JM, Kaiser LR, Albelda SM. Long-Term Follow-up of Patients with Malignant Pleural Mesothelioma Receiving High Dose Adenovirus Herpes Simplex Thymidine kinase (HSVtk)/ Ganciclovir (GCV) Suicide Gene Therapy, Clinical Cancer Research, 11:7444-7453, 2005.

Research Program II
Genetics, Genomics, and Proteomics for Lung Cancer (with Anil Vachani, Louise Showe, and David Speicher)

We have established an infrastructure to collect tumors, blood samples, and clinical information from patients undergoing surgery for lung cancer. These samples being used in a variety of studies including: 1) prediction of recurrence after lung cancer surgery using immunohistochemical, genetic, or genomic predictors, 2) identification of key genes and proteins that differentiate squamous cell carcinomas from lung cancer or head and neck tumors, 3) identifying white blood cell gene expression profiles to diagnose lung cancer, 4) use of proteomics to identify early biomarkers of lung cancer and mesothelioma.

Vachani, A., Nebozhyn, M., Singhal, S., Beers, M., Litzky, L., Muschel, R., Powell, C., Gaffney, P. Kaiser, L., Marron J., Showe, M.,., Albelda, S., Showe, L M.   Identification of 10 Gene Classifier for Head and Neck Squamous Cell Carcinoma and Lung Squamous Cell Carcinoma: Towards a Distinction between Primary and Metastatic Squamous Cell Carcinoma of the Lung, Clinical Cancer Research, 13:2905-2915, 2007.

Singhal, S., Vachani, A., Antin-Ozerkis, Kaiser, L.R., Albelda, S.M.  Prognostic implications of cell cycle, aopoptosis, and angiogenesis biomarkers in non-small cell lung cancer. Clin Cancer Res. 11:3974-3986, 2005.

Research Program III
Pulmonary Vascular Immunotargeting

This project is focused on using monoclonal antibodies directed against pulmonary endothelial antigens conjugated to specific proteins or genes that are used to target the pulmonary circulation. Using this approach, we have delivered marker proteins, oxidant producing enzymes, or anti-oxidant enzymes in large amounts to the pulmonary circulation of mice, rats, and pigs. Delivery of oxidant enzymes results in specific endothelial cell oxidant injury similar to that seen in the acute respiratory distress syndrome. Anti-oxidant delivery is being used to test the importance of delivery of anti-endothelial cell anti-oxidants in animal models of radiation lung injury, ischemia-reperfusion, lung transplantation, hyperoxia, and cardiopulmonary bypass.

Representative Publications:

Ding, B-S, Nankang Hong N, Christofidou-Solomidou, M, Gottstein, C, Albelda, SM,  Cines, DB, Fisher, AB, Muzykantov, V.   Anchoring Fusion thrombomodulin to the Endothelial Lumen Protects Injury-Induced Lung Thrombosis and Inflammation.  Am. J. of Respir. Crit. Care Medicine, in press.
Garnacho, C, Vladimir Shuvaev,V., Thomas, A., McKenna,L., Sun, J., Koval, M., Albelda, S.M., Muzykantov,V., and Muro, S. RhoA activation and actin reorganization involved in endothelial CAM-mediated endocytosis of anti-PECAM carriers: critical role for tyrosine 686 in the cytoplasmic tail of PECAM-1.  Blood, 111:3024-3033, 2008.
V.Shuvaev, M.Christofidou-Solomidou, A.Scherpereel, E. Simone,  E.Arguiri, S.Tliba, J.Pick, S.Kennel, S.Albelda and V.R.Muzykantov* (2007) Factors modulating the delivery and effect of enzymatic cargo conjugated with antibodies targeted to the pulmonary endothelium” J. Controlled Release, 118:235-244, 2007
Ding, B-S, Gottstein, Grunow, A, Kuo, A, Ganguly, K., Albelda, S.M., Cines, D.B., Muzykantov, V.R. Endothelial targeting of a recombinant construct fusing a PECAM-1 single-chain variable antibody fragment (scFv) with pro-urokinase facilitates prophylactic thrombolysis in the pulmonary vasculature.  Blood,106:4191-4198, 2005.

Christofidou-Solomidou, M., Scherpereel, A., Ng, K., Wiewrodt, R., Murciano, J.-C., Kennel, S., Albelda, S.M., Muzykantov, V.R. Antibody-directed targeting of catalase to the endothelial antigen PECAM augments pulmonary antioxidant defense in vivo. Am. J. Physiol.: Lung Cell Mol. Physiol., 285: L283-292, 2003.