Academic Faculty - Valsala Haridas, Ph.D.

Valsala Haridas, Ph.D. Back Next
Research Associate
mail: 1515 Holcombe Blvd. Box 0041 Houston, TX 77030 phone: 713/745-1147 e-mail: vharidas@notes.mdacc.tmc.edu Education: B.S., Zoology, Madras University, India, 1986 M.S., Life Sciences, Jawaharlal Nehru University, New Delhi, India, 1988 Ph.D., Immunology, Jawaharlal Nehru University, NewDelhi, India, 1994
Professional Experience:
Research Associate, University of Texas M. D. Anderson Cancer Center, Houston, TX, 12-99 - Present. Postdoctoral Fellow, University of Texas M. D. Anderson Cancer Center, Houston, TX, B.B. Aggarwal, Ph.D., 04/96-05/98 Postdoctoral Fellow, University of Texas M. D. Anderson Cancer Center, Houston, TX, J.U. Gutterman, M.D., 05/98-12/99 return to top
Research Interests :
We have recently identified a mixture of triterpenoid saponins from an Australian desert legume plant Acacia victoriae that induces cytotoxicity against a wide variety of human hematopoetic and solid tumor cell lines. It shows minimal cytotoxicity against nontransformed cells. Purification of this mixture has yielded two biologically pure components containing an acacic acid core with two acyclic monoterpene units connected by a quinovose sugar. These pure products have been called avicins. To study the mechanism underlying the cytotoxic activity of avicins we chose Jurkat cells which are highly sensitive to these agents. We have demonstrated that the mixture of triterpenoid saponins and avicins induce apoptosis in the Jurkat human T cell line by directly affecting mitochondrial function. Release of cytochrome c occurs within 30 minutes to 2 hours post-treatment followed by activation of caspase-3 and cleavage of poly (ADP-ribose) polymerase (PARP). Interestingly, in the treated cells no significant changes in the membrane potential preceded or accompanied cytochrome c release. A small decrease in the generation of reactive oxygen species (ROS) was measured. We are presently trying to understand how these agents effect the mitochondrial pore and lead to cytochrome c release. We have also shown that in Jurkat cells the mixture of triterpenoid saponins and avicins inhibit TNF induced NF-kB. This suggests an anti-inflammatory property which is in agreement with the potent invivo anti-inflammatory effects observed previously in a mouse skin carcinogenesis model . These agents were also found to decrease the expression of inducible nitric oxide synthase (iNOS). This could have significant implications in the process of carcinogenesis since overexpression of iNOS has been shown to be involved in the pathogenesis of some cancers such as colon cancer. Thus, these triterpenoid saponins, appear to interrupt critical pathways in a transformed cell and could result in the potential discovery of novel drugs. return to top
Selected Publications:
Haridas, V., Ni, J., Meager, A., Su, J., Yu, G-L., Zhai, Y., Kyaw, H., Akama, K.T., Jingru, H., Van Eldik, L.J., and Aggarwal, B.B. TRANK, A novel cytokine that activates NF-kB and c-jun N-terminal kinase. J. Immunol. 161: 1-6, 1998. Haridas, V., Darnay, B.G., Heller, R., and Aggarwal, B.B. Overexpression of the p80 TNF receptor leads to TNF-dependent apoptosis, NF-kB activation and c-jun kinase activation. J. Immunol. 160, 3152-3162: 1998. Darnay, B.G., Haridas, V., Ni, J., Moore, P.A., and Aggarwal, B.B. Characterization of the intracellular domain of receptor activator of NF-kB (RANK). J. Biol. Chem. 273: 20551-55, 1998. Kwon, B.S., Wang, S., Udagawa, N., Haridas, V., Lee, Z.H., Kim, K.K., Oh, K-O., Greene, J., Li, Y., Su, J., Gentz, R., Aggarwal, B.B., and Ni, J. A new member of the tumor necrosis factor superfamily TR1, induces fibroblast proliferation, and inhibits osteoclastogenesis and bone resorption. FASEB J. 12: 845-854, 1998. Pan, G., Bauer, J.H., Haridas V., Wang, S., Yu, G., Vincenz, C., aggarwal, B.B., Ni, J., and Dixit, V.M. Identification and functional characterization of DR6, a novel death domain-containing TNF receptor. FEBS Letters 431: 351-356, 1998. return to top