Raj Kishore, PhD
Professor, Center for Translational Medicine
Director, Stem Cell Therapy Program, Center for Translational Medicine
- Contact Information
- About Me
Research in the Kishore laboratory is focused on several specific areas within the overall theme of identifying novel insights into cardiovascular disease mechanisms and the translational integration of mechanistic studies in relevant physiological models. The major focus of ongoing research encompasses multiple aspects of stem cell based therapies for post-infarct myocardial and other ischemic tissue repair and regeneration. The laboratory is currently investing significant efforts on developing novel strategies to enhance the therapeutic benefits of stem cell therapy (of both adult and embryonic/ iPS cells) specifically their survival, function, and differentiation both in vitro and in physiologically relevant in vivo models of myocardial injury. Some of the strategies include epigenetic modifications, use of nano-biomaterials and co-therapy with anti-inflammatory cytokines. The lab is also developing cell-free, stem cell derived exosomes as a viable alternate to cell-based therapies. Another area of major research focus in the Kishore lab is to delineate mechanisms of Interleukin-10 mediated attenuation of cardiovascular injury and inflammation. These studies have an overall focus to understand the role of inflammation in exacerbating post-injury myocardial functions and tissue repair. The strategy involves utilizing IL-10, a potent anti-inflammatory cytokine, to inhibit the expression of pro-inflammatory and pro-fibrotic mediators. Past studies delineated the mechanisms by which IL-10 imparts its inhibitory action and showed that on molecular level, IL-10 acts mainly via post-transcriptional de-stabilization of mRNA half-life by suppressing mRNA stabilizing protein HuR which binds to mRNAs harboring specific A+U rich sequences in their 3’ untranslated regions. Recent studies from the lab, expanded to a number of myocardial and vascular injury models, have established that IL-10 and its direct downstream signaling targets not only modulated myocardial inflammation but also impart a number of other biological benefits and greatly attenuates injury induced adverse cardiac remodeling. Current studies in this area are focused upon understanding the role and mechanisms of IL-10-mediated inhibition of cardiac fibrosis, especially in the context of bone marrow derived fibroblast progenitor cells.
- Education, Training & Credentials
- PhD, University of Lucknow, 1995
- MD, University of Lucknow, 1988
- Undergraduate Degree, University of Lucknow, 1986
- American Association of Immunologists
- American Heart Association
- American Stroke Association
- Research Society on Alcoholism
- American Association for the Advancement of Science
Srikanth GVN, Krishnamurthy P, Verma SK, Kishore R. Endothelial Progenitor Cells: Application in Vascular Medicine. In Stem Cell Therapy for Organ Failures; Eds. S Indumathi; Springer; 2014 (in Press).
Kishore R, McMullen MR, Cocuzzi E, and Nagy LE. Stabilization of TNF-alpha mRNA contributes to increased lipopolysaccharide-stimulated TNF-alpha production by Kupffer cells after chronic ethanol feeding. Cells of the Hepatic Sinusoid. Eds E Wisse and R Knook; 23-27, 2003.
Kishore R and DW Losordo. Human Bone Marrow Derived Cells and Myocardial Repair and Regeneration. Leri A, Anversa P, Frishman eds Cardiac Regeneration and Stem Cell Therapy, Blackwell publications, pp178-86, 2007.
Kishore R and Hoxha E. Induced Pluripotent Cells in cardiovascular Biology: Epigenetics, Promises and Challenges. In Conn P. Michael, Tang Y (eds.) Progress in Molecular Biology and Translational Science, Vol. 111: Genetics of Stem cells, Elsevier Inc. Publishers: 1-25, 2013.
Krishnamurthy P, Verma SK, Kishore R. Murine Bone marrow Transplantation Model. In Bolli R, Losordo DW, Ardehali H (eds), Manual of Research Techniques in Cardiovascular Medicine; Wiley-Blackwell publishers, Oxford, UK, 2013 (in press).
Verma SK, Krishnamurthy P, Kishore R. Transverse Aortic Constriction: A Model to Study Heart Failure in small animals. In Bolli R, Losordo DW, Ardehali H (eds), Manual of Research Techniques in Cardiovascular Medicine; Wiley-Blackwell publishers, Oxford, UK, 2013 (in press).
Thal MA and Kishore R. Role of cytokines in angiogenesis: Turning it on and off. In, Mehta J and Dhalla s (eds) Biochemical basis of Angiogenesis; Springer Science publishers, pp: 25-51; 2013.
Lambers E and Kishore R. mRNA Stability in cardiac Function and Disease. Current Hypertension Reports: Mediators, Mechanisms and pathways in Tissue Injury section. Volume 14, issue 6, 2013 (in press).
24711449. P Sasi S, Song J, Park D, Enderling H, McDonald JT, Gee H, Garrity B, Shtifman A, Yan X, Walsh K, Natarajan M, Kishore R, Goukassian DA. TNF-TNFR2/p75 Signaling Inhibits Early and Increases Delayed Non-Targeted Effects in Bone Marrow-Derived Endothelial Progenitor Cells. J Biol Chem. 2014 Apr 12. [Epub ahead of print]