Department of Medicine

Vascular Biology Research Laboratory

The Vascular Biology Research Laboratory at the Cardiovascular Institute is a dynamic group of individuals led by Dr. Kaikobad Irani. It has a central mission of advancing our understanding of mechanisms important in vascular homeostasis and disease. There is a broad spectrum of ongoing and planned research within our group, ranging from in vitro studies using recombinant proteins, to signal transduction in cell culture models, to animal physiology in transgenic and knockout/knockdown mice, to translational genetic research in humans. The laboratory places great emphasis on deciphering fundamental mechanisms to gain novel insights into vascular diseases such as hypertension and arteriosclerosis, and to investigating the clinical importance of these discoveries. The laboratory is supported by federal and institutional funds. Some past and present work in the laboratory includes:

• Establishing the role of Apurinic/Apyrimidinic Endonuclease1/Redox factor-1 (APE1/Ref-1) in the endothelial nitric oxide and reactive oxygen species production, and in the control of vascular tone.
• Establishing the importance of the rac1 GTPase in ischemia-reperfusion injury
• Establishing the importance of the p66shc adaptor protein in the regulation of endothelial nitric oxide production.
• Determining the relationship between the rac1 GTPase and the p66shc adaptor protein, and the impact of this relationship on endothelial nitric oxide and reactive oxygen species production.

Present members of the laboratory are:

• Kaikobad Irani, M.D., Associate Professor.
• Tohru Yamamori, D.V.M., Ph.D., Research Associate
• Ilwola Mattagajasingh, Ph.D., Research Associate.
• Asma Naqvi, M.S., Research Tech V, and laboratory manager.
• Jeremy DeRicco, Research Tech IV.
• Cuk Seong Kim, Ph.D., Research Associate
• Saet-Byel Jung, Ph.D., Research Associate.
• Timothy Hoffman, Research Tech V.

Lab photograph. From left to right: Saet-Byel (Venus) Jung, Tohru Yamamori, Jeremy DeRicco (back), Ilwola Mattagajasingh, Kenji Kasuno, Timothy Hoffman, Kaiko Irani (back), Cuk-Seong Kim, Asma Naqvi..

Select past members of the laboratory with current academic appointments include:

• Michitaka Ozaki, M.D., Ph.D.  Associate Professor of Surgery, Hokkaido University, Japan.
• Firdous A. Khanday, Instructor, Dept. of Biotechnology, University of Kashmir, India.
• Byeong Hwa Jeon, M.D., Ph.D., Associate Professor and Chairman, Dept of Physiology, Chungnam National University, Korea.
• Young Chul Park, Ph.D., Research Faculty, Department of Anatomy and Cell Biology, Dong-A University College of Medicine, Korea
• Yan-Xia Liu, M.D., Associate Professor, and Dean of Basic Medical Sciences, Tianjin Medical University, China.

Some recent publications from the laboratory are:

• Kasuno K, Naqvi A, Dericco J, Yamamori T, Santhanam L, Mattagajasingh I, Yang S, Meyskens FL, Bosserhoff AK, Irani K. Antagonism of p66shc by melanoma inhibitory activity. Cell Death Differ. 2007 Apr 13.
• Firdous A. Khanday, Lakshmi Santhanam, Kenji Kasuno, Tohru Yamamori, Asma Naqvi,  Jeremy DeRicco, Artem Bugayenko, Ilwola Mattagajasingh, Andrea Disanza, Giorgio Scita, and Kaikobad Irani. Sos-mediated activation of rac1 by p66shc. J Cell Biology, 13;172(6):817-22; 2006.
• Khanday FA, Yamamori T, Mattagajasingh I, Zhang Z, Bugayenko A, Naqvi A, Santhanam L, Nabi N, Kasuno K, Day BW, Irani K. Rac1 Leads to Phosphorylation-dependent Increase in Stability of the p66shc Adaptor Protein: Role in Rac1-induced Oxidative Stress. Mol Biol Cell. 2006 17(1):122-9.
• Tohru Yamamori, Anthony R. White, Ilwola Mattagajasingh, Firdous A. Khanday, Azeb Haile, Bing Qi, Byeong Hwa Jeon, Artem Bugayenko, Dan E. Berkowitz, Kaikobad Irani. P66shc regulates endothelial NO production and endothelium-dependent vasorelaxation: implications for age-associated vascular dysfunction. J Mol Cell Card. 2005 Dec;39(6):992-5.
• Byeong Hwa Jeon, Gaurav Gupta, Young Chul Park, Bing Qi, Azeb Haile, Firdous A. Khanday, Yan-Xia Liu, Jin‑Man Kim, Michitaka Ozaki, A. Ronald White, Dan E. Berkowitz, and Kaikobad Irani. Apurinic/Apyrimidinic Endonuclease 1 regulates endothelial nitric oxide production and vascular tone. Circ Res. 95; 902-910: 2004.
• Shailesh S Deshpande, Bing Qi, Young Chul Park, and Kaikobad Irani. Constitutive activation of rac1 results in mitochondrial oxidative stress and induces premature endothelial cell senescence. Arterioscler Thromb Vasc Biol 23;e1-6: 2003

For more information about our research and opportunities in our laboratory, please contact:

Kaikobad Irani, M.D.
E-mail: iranik@upmc.edu