 |
|
|
Usha Ponnappan, Ph.D.
Professor, Department of Microbiology & Immunology Immunology Research Interest: Aging and immune regulation Ph.D., University of Bombay, India Postdoctoral, University of Toronto, Toronto, Canada Phone: (501) 296-1252 Research Description Research in my laboratory is focused on understanding signal transduction in T lymphocytes. Using aging as a model system for immune dysregulation, our studies have delineated the regulation of transcription factor, Nuclear factor kappa B, during aging. Our long-term research objective is to identify changes in T cell signal transduction cascades relevant to the initiation and manifestation of immune dysregulation. Current areas of research in my laboratory include, (a) transcriptional regulation and transcriptional cross talk in immune regulation/dysregulation; (b) Ubiquitin Proteasome pathway and immune senescence; (c) oxidative stress and proteasomal dynamics in T cell function (d) ubiquitination and deubiquitination in innate and adaptive immunity and (e) Upregulation of Ubiquitin proteasome pathway in immune potentiation. Through studies in our laboratory, we have now clearly defined age-associated changes in signal transduction as it relates to immune function. Using splenic T lymphocytes from long-lived strains of mice and human peripheral blood T lymphocytes from young (21-30 years) and elderly (65-80 years) human donors, we have now demonstrated significant changes in signal induction and amplification. These changes occur both in early events such as activation and induction of phospho-tyrosine kinases such as p56lck and downstream events such as the induction and regulation of transcription factor NF k B. Our key finding of lowered enzymatic activity associated with the proteasome during aging in the immune apparatus is likely to shed light on diverse age-related processes such as T cell repertoire skewing, accumulation of aberrant proteins and protein turn-over in the elderly, multi-ubiquitinated protein deposits in senile dementia, lowered responses to viral antigens and defects in cell cycle regulation during proliferation and apoptosis in the elderly. References S . Ponnappan, S.J. Cullen and U. Ponnappan (2005) Constitutive degradation of IkBa in primary human T lymphocytes is mediated by calpain. BMC: Ageing and Immunity 2:15. S.Ponnappan and U. Ponnappan (2004). Age-associated alterations in proteasomal subunits may underlie defect in function during aging. International Proceedings, Immunology 2004. E718C1104, 171-175. U. Ponnappan, F.E. Yull and Soderberg, L.S.F. Inhaled isobutyl nitrite inhibited macrophage inducible nitric oxide by blocking NFkB signaling and promoting degradation of inducible nitric oxide synthase-2. (2004) Int. Immunopharm, 4:1231-1239. S. Ponnappan, G.U-Trebilcock, M.Lidquist and U. Ponnappan Tyrosine phosphorylation-dependent activation of NFkB is compromised in T cells from the elderly. (2004) Exptal. Geron. 39.:559-566 Ponnappan Usha and Ponnappan Subramaniam (2003) Ubiquitin-proteasome pathway in immune senescence ( invited review). Recent Research developments in Biochemistry 4:779-793. Ponnappan, U. Ubiquitin-Proteasome pathway is compromised in CD45RO+ and CD45RA+ T lymphocyte subsets during aging. (2002) Experimental gerontology 37, 359-367.
Questions about this page? Send us an email. |
 |
||||||||||||||||||||||||||||||||||||||
