Dr. Tirumalai Rangasamy
Pathobiological Sciences (PBS)
The overall goal of my research program is to identify the genetic mechanisms of susceptibility to oxidative stress related lung diseases such as cigarette smoke (CS)–mediated chronic obstructive pulmonary disease (COPD), allergic asthma, bacterial pneumonia and septic shock. Our long term objectives are 1) to identify the host factors that determine the susceptibility to CS-induced COPD, allergic airway inflammation, bacterial pneumonia, and acute lung injury and septic shock, using genetic, genomic, and proteomic methods which are especially valuable in the study of complex disease conditions, 2) to identify and characterize specific molecular pathways that are associated with COPD and asthma, 3) to investigate the role of the major anti-oxidative transcription factor Nrf2 in dendritic cell activation, T cell differentiation, and in stem cell differentiation, and 4) to develop small molecule/stem cell based therapeutic interventions in oxidative stress related lung diseases. I have extensive expertise in mouse models of inflammatory lung diseases including CS-induced pulmonary emphysema, allergic asthma, bacterial pneumonia and endotoxin/cecal ligation and puncture mediated acute lung injury and septic shock; lung morphometric measurements (measurement of alveolar size, septal thickness, mean linear intercept, and surface to volume ratio using Metamorph software program); measurement of lung elastance and resistance in asthmatic mice; isolation and characterization of bone marrow and lung derived mesenchymal stem cells; generation of myeloid dendritic cells/macrophages/neutrophils from bone marrows, differentiation of Th1/Th2/FOX P3 regulatory T cells, bacterial culture, extracellular and intracellular (opsonophagocytosis) bacterial killing assays, gene expression arrays (Affymetrix), expression (in E. coli) and purification of (using FPLC) recombinant protein (riboflavin carrier protein(riboflavin carrier protein), development of contraceptive vaccine (riboflavin carrier protein; using mice rats and rabbits) and epitope mapping, overexpression of gene (Nrf2) using lentiviral particles, validation of marker gene (s) expression using qPCR, lung pathology, flow cyotometry, in vitro cell-culture experiments, as well as in various immunological and molecular techniques. I am currently developing lung mesenchymal stem cell based intervention in chronic obstructive pulmonary disease (COPD)-associated bacterial exacerbations, as well as in various infectious lung diseases including pneumonia caused by Klebsiella pneumoniae, Streptococcus pneumoniae (Pneumococcal pneumonia), and superbugs [methicillin resistant Staphylococcus aureus (MRSA), and carbapenem resistant Klebsiella pneumoniae]. The accomplishment of these goals will require multidisciplinary research that coordinates basic scientific and clinical investigations.
Identification of first COPD (pulmonary emphysema) resistance gene (Rangasamy et al. 2004. J Clin. Invest.).
Proving oxidant-antioxidant hypothesis in the pathogenesis of COPD [Rangasamy et al. 2004. J Clin. Invest.], and allergic asthma [Rangasamy et al. 2005. J Exp Med.] using relevant animal models.
2011- 2013 ISRN Pathology
2012- 2014 Dataset Papers in Medicine
2013- 2015 World Journal of Respirology
2018- Present Journal of Physiological and Biomedical Sciences
2020- Present Frontiers in Toxicology (Review Editor in Immunotoxicology)
NIH-RO1 Grant: Host Immunity in Sepsis-Induced Systemic Infection. 05/01/21 – 04/30/26.
NIH-P20 Pilot Grant: LMSCs based intervention in emphysema-associated bacterial exacerbation. 05/25/21 – 12/31/21.
NIH-P20 Center Grant: Center For Lung Biology and Disease. 01/02/19 – 12/31/23.
NIH-RO1 Grant: Innate Immunity in Sepsis. 06/01/18 – 05/31/23.
NIH-R21 Grant: Role of Lung Mesenchymal Stem Cells in Pneumonia-induced Sepsis. 12/07/17 – 11/30/21.
NIH-P20 Pilot Grant : Role of LMSCs in SHS-mediated bacterial exacerbation.09/16/19 – 12/31/19.
Competitive Research Program Funds: Modulation of Neutrophil Function by Lung Mesenchymal Stem Cells in Pneumonic Sepsis. 07/01/2016-6/30/17.
NIH-COBRE/CEIDER Pilot Grant: Sca1+ LMSC Based Intervention in Bacterial Pneumonia. 10/01/2015 – 09/30/2016.
New York Stem Cell Foundation: Pre-Clinical Evaluation of Nrf2 Over Expressing MSC in Pulmonary Emphysema. 09/01/10 - 02/28/13.
NIH-R01 Grant: Lysophosphatidic acid and Edg receptors in the pulmonary immune response. 08/15/10 - 05/31/14.
NIH-R01 Grant: PPAR gamma as a Therapeutic Target in COPD.04/01/11 - 12/31/14
NIH-R01 Grant: Unique aspects of respiratory immunity. 07/01/12 - 12/31/14.
NIH Super Pilot Grant: Cigarette Smoke, Oxidative Stress and Lung Inflammation. Funded by the University of Rochester Center for Translational Science Institute. 08/01/12 - 07/31/14.
FDA/NIH/NHLBI R01 Grant: Comparative Transcriptomic Signatures of Inhaled Tobacco Smoke. 7/1/14-12/31/14.
NIH/NHLBI UO1 Grant: Biorepository for Investigation of Neonatal Diseases of Lung-Norma (BRINDL-NL). 4/2/14-12/31/14