Usha Ponnappan, Ph.D.

Adjunct Professor, Department of Microbiology & Immunology 

Research Interest: Aging and immune regulation
Ph.D., University of Bombay, India
Postdoctoral:  University of Toronto, Toronto, Canada
Phone: (501) 296-1252
Fax:     (501) 686-5359

E-mail 

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

Compensatory increase in USP14 activity accompanies impaired proteasomal proteolysis during aging.  Ponnappan S, Palmieri M, Sullivan DH, Ponnappan U. Mech Ageing Dev. 2013 Jan-Feb;134(1-2):53-9. doi: 10.1016/j.mad.2012.12.007. Epub 2013 Jan 3.

Altered regulation of CXCR4 expression during aging contributes to increased CXCL12-dependent chemotactic migration of CD4(+) T cells. Cané S, Ponnappan S, Ponnappan U. Aging Cell. 2012 Aug;11(4):651-8. doi: 10.1111/j.1474-9726.2012.00830.x. Epub 2012 Jun 4.

Impairment of non-muscle myosin IIA in human CD4+ T cells contributes to functional deficits in the elderly. Cane S, Ponnappan S, Ponnappan U. Cell Mol Immunol. 2012 Jan;9(1):86-96. doi: 10.1038/cmi.2011.41. Epub 2011 Oct 10

Proteasome inhibition up-regulates inflammatory gene transcription induced by an atypical pathway of NF-kappaB activation. Cullen SJ, Ponnappan S, Ponnappan U. Biochem Pharmacol. 2010 Mar 1;79(5):706-14. doi: 10.1016/j.bcp.2009.10.006. Epub 2009 Oct 14.

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