Shanmugam Nagarajan, PhD
Associate Professor of Pathology
Dr. Nagarajan is a member of the Division of Experimental Pathology and a member of the Cellular and Molecular Pathology Graduate Training Program.
200 Lothrop Street
Pittsburgh, PA 15213
Office Telephone: 412-648-8811
Lab Telephone: 412-648-8469
- MSc - 1982, Christian Medical College, Vellore, and University of Madras, India
- PhD - 1988, Christian Medical College, Vellore, and University of Madras, India
There are three major areas of research in Dr. Nagarajan's laboratory. In the first project my laboratory is investigating the role of auto-antibodies, specifically antibody against oxLDL in the initiation and progression of atherosclerosis. Moreover because of the central role of modulation of immune system in chronic diseases, his laboratory is interested in understanding the role of immune system in pathophysiology of atherosclerosis. Recent studies have suggested that generation of oxidative products of LDL (oxLDL) is one of the risk factors implicated in the pathogenesis of atherosclerosis. OxLDL induces an autoimmune response as evidenced by the presence of anti-oxLDL IgG in atherosclerotic lesions in patients and animal models. Moreover the titer of autoantibodies against oxLDL correlates with the progression of atherosclerosis in humans and in the hyperlipidemic mouse model. This raises a possibility that in oxLDL-immune complexes binding to Fcγ receptors (FcγR) may contribute to the progression of atherosclerosis. These receptors also play a major role in IC-mediated tissue injury in autoimmune inflammatory disease. FcγRs are classified into activating and inhibitory receptors. Activating FcγRs are involved in cellular functions such as phagocytosis of antibody-opsonized particles, and inflammatory responses. The inhibitory FcγR (CD32B) regulates the inflammatory response initiated by the activating FcγRs and control antibody production by regulating B lymphocyte activation. OxLDL-IC generated during hyperlipidemia could bind to the activating and/or inhibitory FcγRs present in human atherosclerotic lesions and contribute to the inflammatory processes. The central hypothesis of our research focus is that FcγRs play an important role in the progression of atherosclerosis.
In the second project Dr. Nagarajan's research centers on the global issue of how dietary factors modulate the immune system to prevent chronic inflammatory diseases including atherosclerosis. Epidemiological reports suggest that cardiovascular incidence is lower in Asian population. It is plausible that the diets such as soy and rice may modulate the immune system, thus preventing atherosclerotic lesions. In recent studies we have determined that the progression of atherosclerotic lesions were strikingly reduced in soy protein fed hyperlipidemic animal models. There are two major components with potential bioactivity in soy diet or soy protein isolates: phytochemicals such as isoflavones associated with soy protein, and peptides generated from two of the major soy proteins such as β-conglycinin (or 7S globulins) and glycinin (or 11S globulins). We have recently identified isoflavone-free soy protein inhibits the progression of atherosclerosis by blocking inflammatory cytokine/chemokine responses and inflammation induced VCAM-1 expression. Interestingly, maternal hypercholesterolemia has been implicated with a higher incidence and earlier onset of atherosclerotic lesions in neonatal offspring. Currently, we are investigating whether in utero exposure to isoflavone-free soy protein isolate (SPI) diet primes the vessel wall to attenuate development of atherosclerosis in adult life of F1 offspring. Specifically we are studying the effect of in utero dietary exposure of soy or soy derived compounds in preventing chronic inflammatory diseases such as atherosclerosis.
Recent studies have suggested that pathogen-induced inflammation at sites distant from the infection site contributes to the initiation and progression of atherosclerosis. The contribution of urogenital infection with C. muridarum has never been studied in cardiovascular pathogenesis. Recently we have undertaken studies to determine the causal link between genital Chlamydia induced inflammatory responses promoting atherosclerosis. Preliminary studies have established Chlamydia genital infection results in enhanced atherosclerosis in hyperlipidemic mouse models. Currently we are pursuing studies to understand molecular mechanism(s) contributing to the enhanced atherosclerosis during genital Chlamydia infection.
SpecialtiesImmunology, autoimmune diseases, inflammatory diseases
Awards and Honors
- Predoctoral Junior Research Fellowship, Council of Scientific and Industrial Research, India - 1982 85
- Predoctoral Junior Research Fellowship, University Grants Commission, India - 1985 86
- Predoctoral Senior Research Fellowship, Council of Scientific and Industrial Research, India - 1985 88
- Scientist Development Award, American Heart Association, National Center, Dallas, TX - 2001 05
- Lyon New Scientist Development Award, Arkansas Children's Hos Research Institute, Little Rock, AR - 2003 05
- American Association of Immunologists Annual meeting Travel Grant Award - 2011
Selected PublicationsView Dr. Nagarajan's publications on PubMed
- Ng HP, Zhu X, Harmon EY, Lennartz MR, Nagarajan S. Reduced atherosclerosis in apoE-inhibitory FcγRIIb deficient mice are associated with increased anti-inflammatory responses by T cells and macrophages. Arteriosclerosis, Thrombosis and Vascular Biology 35: 1101- 1112, 2015.
- Harmon EY, Fribgifer III V, Keller RS, Zhu X, Aviram D, Jones DM, Nagarajan S, Lennartz MR. Anti-inflammatory skewing is atheroprotective: Role of FcγRIIb. Journal of American Heart Association Dec;3(6):e001232, 2014.
- Kaynar AM, Yende S, Zhu L, Frederick DR, Chambers R, Carter M, Stolz DB, Agostini B, Gregory A, Nagarajan S, Shapiro SD, Angus DC. A murine model of long-term cardiovascular consequences of sepsis Critical Care 18:469 doi: 10.1186/s13054-014-0469-1.
- Zhu X, Ng HP, Lai YC, Craigo JK, Nagilla PS, Raghani P, Nagarajan S. Scavenger receptor function of mouse Fcγ receptor III contributes to progression of atherosclerosis in apolipoprotein E hyperlipidemic mice. Journal of Immunology 193: 2483-2495, 2014.