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 230 peer-reviewed papers, along with numerous review articles and book chapters. He has spoken at and chaired numerous national and international meetings.

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 series of Phase 1 clinical trials for patients with mesothelioma are currently underway. Current trials are studying immunogene therapy using an adenovirus that delivers the interferon-alpha gene and the use of an antibody against TGF-beta. Our major area of recent interest in the lab is augmentation of anti-tumor immune effects using COX-2 inhibitors, TGFbeta inhibitors, and chemotherapeutic drugs.  We are also characterizing the importance of tumor-associated macrophages and neutrophils.  Most recently we are exploring the utility of using genetically altered T-cells to target mesothelioma.   Opportunities are also available for translational work analyzing immune endpoints from patient samples collected in the trials. 

Sterman DH, Haas AR, Moon E, Recio A, Schwed D, Vachani A, Katz S, Gillespie C, Cheng GJ, Sun J, Papasavvas, E, Montaner LJ,  Heitjan DF, Litzky  L, Friedberg J, Culligan M,  June CH, Carroll RG, Albelda SM,  A Trial of Intrapleural Adenoviral-mediated Interferon-alpha2b Gene Transfer for Malignant Pleural Mesothelioma. Am J Respir Crit Care Med. In press, 2011.

Fridlender, Z.G., Sun, J., Singhal, S.,  Kapoor, V., G., Cheng, G., Suzuki, E., Albelda, S.M.  Chemotherapy Delivered After Viral Immuno-Gene Therapy Augments Anti-tumor Efficacy via Multiple Immune-Mediated Mechanisms,  Mol. Therapy, 18:1947-59, 2010.

Zhao Y, Moon E, Carpenito C, Paulos CM, Liu X, Brennan AL, Chew A, Carroll RG, Scholler J, Levine BL, Albelda SM, June CH.    Multiple injections of electroporated autologous T cells expressing a chimeric antigen receptor mediate regression of human disseminated tumor.  Cancer Research, 70:9053-61, 2010

Sterman D.H., Recio A., Haas A.R., Vachani A., Katz S.I., Gillespie C.T., Cheng G., Sun J., Moon E., Pereira L., Wang, X., Heitjan D.F., Litzky, L., June, C.H., Vonderheide R.H., Carroll R.G., Albelda, S.M. A Phase I Trial of Repeated Intrapleural Adenoviral-Mediated Interferon Beta Gene Transfer for Mesothelioma and Metastatic Pleuarl Effusion.  Molecular Therapy, 18:852-860, 2010.

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, 16:183-194, 2009. 

 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- 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.

Research Program II
Genetics and Genomics for Lung Cancer and Mesothelioma (with Anil Vachani )

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, initiating personalized medicine.

Representative publications

Matsumura, K., Opiekun, M., Oka, H., Albelda S.M., Yamazaki, K., Beauchamp, G.K., Identification of  urine odor signatures in mouse models of lung cancer, PLoS ONE, 5(1): e8819.- 2010. 

Showe M.K., Vachani A., Kossenkov A.V., Yousef, M., Nichols, C., Nikonova E.V., Chang, C., Kucharczuk, J., Tran, B. Wakeam, E., Yie T.A., Speicher, D.A., Rom, W.N., Albelda,S.M., Showe, L.C. Diagnosis of Non-small cell lung cancer from peripheral blood gene expression.  Cancer Research, 69:9202-10, 2009.

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.

Research Program III
Pulmonary Vascular Immunotargeting Program Summary  (with Vladimir
Muzykantov and Melpo Christofidou)

This project is conducted in close collaboration with Dr. Vladimir Muzykantov in the Department of Pharmacology.   It 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:

Shuvaev, VV, Tliba, S, Pick, J, Arguiri E, Christofidou-Solomidou M, Albelda, SM, Muzykantov, VR: Modulation of endothelial targeting by size of antibody-antioxidant enzyme conjugates. J Control Release 149: 236-241, 2011.

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, 180:247-56, 2009.

Dziubla, T.D., Shuvaev, V.V., Hong, N.K.,  Hawkins, B.,  Muniswamy, M.,  Takano, H.,  Simone, E.,   Nakada, M.T., Fisher, A.F., Albelda, S.M.,  and Muzykantov, V.M.  "Endothelial Targeting of Semi-permeable Polymer Nanocarriers for Enzyme Therapies." Biomaterials  29:215-27, 2008.

Ding, B., Hong, N, Murciano, JC, Ganguly, K, Gottstein, C, Christofidou-Solomidou, M, Albelda, SM, .Fisher A, Cines, D, and Muzykantov, VR. Prophylactic thrombolysis by thrombin-activated latent pro-urokinase targeted to PECAM-1 in the pulmonary vasculature. Blood,  111:1999-2006; 2007