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Current research is directed at understanding mechanisms of human B cell lymphomagenesis, transcriptional control of cyclosporin A, and FK506 mediated immunosuppression and metabolic treatment of HIV-1 infection. Techniques in immunology, molecular and cell biology are used. In one project, we are investigating potential roles of cytokines and key cell cycle regulators during Epstein-Barr virus-mediated or AIDS-associated B cell transformation. We are currently focusing on TGF-beta-sensitive cyclin/cdk complexes and their inhibitors to evaluate potential drugs for lymphoma. In another project, we have cloned and characterized a new molecular target of cyclosporin A belonging to the NFAT transcription factor family. We have shown that cyclosporin A mediates phosphorylation of the NFAT factor which then fails to bind the IL-2 promoter. We will evaluate the physiological significance of multiple phosphorylation sites and the in vivo role of NFAT with gene knockouts. We are also investigating the efficacy of cellular metabolic products to inhibit HIV-1 infection and have found a product that inhibits viral production and protects infected T cells from apoptosis.
Park, J., Yaseen, N.R., Hogan, P.G., Rao, A. & Sharma, S. Phosphorylation of the transcription factor NFATp inhibits its DNA binding activity in cyclosporin-A-treated human B and T cells. J. Biol. Chem. 270:20653-20659, 1995.
Arvanitakis, L., Yaseen, N. & Sharma, S. Latent membrane protein-1 induces cyclin D2 expression, pRb hyperphosphorylation and loss of TGF-beta1-mediated growth inhibition in EBV-positive B cells. J. Immunol. 155:1047-1056, 1995.
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