Tirumalai Rangasamy, Ph.D.

Tirumalai Rangasamy, Ph.D.

Contact Information

University of Rochester Medical Center
School of Medicine and Dentistry
601 Elmwood Ave, Box 692
Rochester, NY 14642

Office: (585) 276-4035
Lab: (585) 276-4094
Fax: (585) 273-1058

Research Bio

Oxidants/Antioxidants Imbalance in Chronic Obstructive Pulmonary Disease (COPD) and Allergic Asthma.



Our research interests relate to the balance between oxidants and antioxidants in obstructive lung diseases. Both COPD and asthma afflict more than one billion people in the world and 15-20% US population. Even though oxidative stress is suspected to be involved in the pathogenesis of asthma and COPD, it has been difficult to define relevant mechanistic pathways due to lack of good animal models. We study a mice deficient in the transcription factor Nuclear erythroid 2 p45 related factor 2 (Nrf2) to specifically dissect out the role of oxidative stress/antioxidants in the pathogenesis of COPD and asthma.Nrf2 is a CNC family of basic leuzine zipper transcription factor which regulates the transcriptional induction of almost all antioxidant and phase II detoxification genes in the lungs. Using gene expression profiling, molecular, immunological, and computer assisted topometric techniques, we found that Nrf2 is a major determinant of susceptibility to COPD and asthma. Disruption of the transcription factor Nrf2 in an emphysema resistant ICR mice strain led to early onset and more severe cigarette smoke-induced pulmonary emphysema [Rangasamy et. al. (2004) J.Clin.Invest. 114(9):1248-59] and asthma [Rangasamy et.al. (2005) J Exp Med. 202(1):47-59] after allergen challenge.


Pulmonary emphysema is one of the major pathological abnormalities associated with COPD. The damage to the lung in pulmonary emphysema is irreversible and available treatments for moderate disease, such as inhaled bronchodilators, provide only limited symptomatic relief. Hence, there is a strong need for new approaches that are capable of halting disease progression and interventions that repair/regenerate alveolar structures are desperately needed. A number of animal and human studies have revealed that tissue-specific stem cells and bone-marrow derived mesenchymal stem cells (MSCs) contribute to lung tissue regeneration and protection and thus administration of exogenous stem/progenitor cells or humoral factors that can activate endogenous stem/progenitor cells may be a potent next-generation therapy for COPD. Mesenchymal stem cells (MSCs) are prime candidates for the repair and regeneration of damaged tissues and organs. Our discovery of Nrf2 as a novel factor for regulating emphysema and other critical lung diseases suggests that it may be possible to target Nrf2 to transcriptionally induce a broad spectrum of antioxidant and cytoprotective pathways. Currently we are investigating the efficacy of Nrf2 overexpressing (using lentivirus) mesenchymal stem cells in regenerating alveolar structures in cigarette-smoke induced pulmonary.

In allergic asthma studies, we are currently exploring the role of oxidative stress sensitive cell cycle inhibitor P21 Cip1 in the activation and maturation of lung dendritic cells and in the proliferation and differentiation T helper cell subsets (effector Th2 cells, memory T cells and T regulatory cells). These studies are conducted in collaboration with Dr. Steve N. Georas and Dr. Michael O'Reilly.

We are also using an automated cigarette smoke machine, imaging and computer assisted topometric techniques to investigate the role of negative regulator (ATF3) of Nrf2 in the pathogenesis of pulmonary emphysema in mice models. Inducible transgenic systems, gene knock-out mice, genomics, and standard molecular biology, biochemical, and immunological techniques are used in the laboratory.

Awards & Honors (National)

Scholar in Training Award for the Meritorius Research Findings | American Association for Cancer Research | Washington DC, USA 2003
Lasker Fellowship | Lasker Foundation | Johns Hopkins University, Baltimore, USA 2002 - 2004
Best Paper Presentation Award (Third) | National Conference on Invertebrate Reproduction | Cannanore, India 1995
Best Paper Presentation Award (First) | National Conference on Reprod. Biol.and Comparat. Endocrinology | Pondichery, India 1994
CSIR-UGC Senior Fellowship Award | Council for Scientific and Industrial Research | Delhi, India 1992 - 1995
Best Paper Presentation Award (First) | National Conference on Reprod. Biolog. and Comp. Endocrinology | Trichy, India 1991
Junior Research Fellowship Award | Council for Scientific and Industrial Research-UGC | Delhi, India 1990

Recent Journal Articles

Showing the 5 most recent journal articles. 15 available »

2009
T. Rangasamy, V. Misra., L. Zhen., C. G. Tankersley., R. M. Tuder, and S. Biswal. "Cigarette Smoke-Induced Emphysema in A/J mice is Associated with Pulmonary Oxidative Stress, Apoptosis of lung Cells, and Global Loss of Gene Expression. Amer. J. Physiol." Lung Cell. Mol. Physiol.. 2009; 296(6): L888-L900..
2009
S.S. An, J. Kim., K. Ahn., X. Trepat., K. J Drake., S. Kumar., G. Ling., C. Purington., T. Rangasamy., T. T. W Kensler., W. Mitzner., J. J. Fredberg., and S. Biswal. "Cell stiffness, contractile stress and the role of extracellular matrix." Biochem. Biophys. Res. Commun.. 2009; 382(4): 697-703..
2009
J. Roman, T. Rangasamy, J.Guo, S.Sugunan, N.Meednu, G.Packirisamy, L.Shimoda, A.Golding, G.Semenza , S.N.Georas. "T Cell Activation Under Hypoxic Conditions Enhances Interferon-gamma Secretion." Am. J. Respir. Cell. Mol. Biol.. 2009; : [Epub ahead of print]..
2009
T.Rangasamy, M.A.Williams, S. Bauer, M.A.Trush, S.N.Georas, S.Biswal. "Nrf2 Inhibits the Maturation Of Murine Dendritic Cells By Ragweed Extract." Am. J Resp. Cell. Mol. Biol.. 2009; .
2008
S.A. McGrath-Morrow, T. Rangasamy, C. Cho, E. Neptune, R. Wise, R. M. Tuder, and S. Biswal. "Cigarette Smoke Causes Structural Damage and Immune Response Gene Inhibition in Neonatal Mouse Lung. 38(4):393-400." Am J Respir Cell Mol Biol.. 2008; 38(4): 393-400. Epub 2007 Nov 1..

Current Appointments

Research Assistant Professor - Department of Medicine, Pulmonary Diseases and Critical Care (SMD) - Primary

Education

Ph.D. | University of Madras, India1997
M.Sc. | University of Madras, India1988
B.Sc. | University of Madras, India1986

Post-Doctoral Training & Residency

Research Associate, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, USA 2007
Post Doctoral Fellow, Johns Hopkins University, Baltimore, USA 2006
Post Doctoral Fellow, INSERM U430, Paris, France 2001
Post Doctoral Fellow, Indian Institute of Science, Bangalore, India. 2000