Brief profile and research contributions

   Dr. Karunagaran is a Professor at the Department of Biotechnology, Indian Institute of Technology Madras, Chennai. He started his career as a lecturer in Biochemistry at the PSG college of Arts and Science, Coimbatore in 1979 and taught a number of BSc and MSc students for more than a decade.He has made significant contributions in the field of signal transduction, mediated by epidermal growth factor receptors (EGFRs) and their ligands implicated in the development of human cancer. A novel concept proposed by him (with Dr. Yosef Yarden from Israel) is that ErbB-2 (the second member of EGFR family) acts as the preferred heterodimeric partner of all the known members of the EGFR family, and at least, part of the transforming ability of an over expressed ErbB-2 is due to transactivation of growth factor signaling. Moderate expression of ErbB-2 is biased for heterodimerization with ErbB-3 and ErbB-4 receptors that bind neu differentiation factor. A monoclonal antibody against neu differentiation factor raised by him is being marketed by a U. S. Company. Dr. Karunagaran (with Dr. Mien-Chie Hung from Houston) discovered that adenoviral E1A suppressed the radiation-induced activation of Nuclear Factor kappa B (NF-κB), a transcription factor known to protect cells from cell death. This finding provides a plausible mechanism for the long-known susceptibility of cells to radiation-induced apoptosis in the presence of E1A.

Dr. Karunagaran joined the Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram in December 1997. His laboratory studies are focused on cervical cancer, an important public health problem for adult women in India. Cervical cancer causes about 250,000 deaths annually worldwide, with women in the developing countries accounting for 80% of these deaths. Although human papilloma virus (HPV) infection is the major risk factor for cervical cancer, molecular alterations of tumor suppressor genes and/or oncogenes either associated with HPV infection or independent of it are necessary for the cervical cancer progression. Dr. Karunagaran has shown that the transcription factor, nuclear factor-kappa B (NF-κB) is constitutively activated in high-grade squamous intraepithelial lesions and squamous cell carcinomas during human cervical cancer progression (cited in text book “the biology of Cancer” on page 195, by Robert A. Weinberg, Garland Science http://www.garlandscience.com/textbooks/0815340788.asp).

Many chemopreventive agents induce programmed cell death or apoptosis, a potent mechanism by which they eliminate preneoplastic or cancer cells. Curcumin, the yellow pigment derived from Curcuma longa, is a pharmacologically safe compound and possesses antioxidant, antiinflammatory and anticancer activities. Curcumin inhibits cell proliferation and induces apoptosis of several, but not all cancer cells. Dr. Karunagaran has proposed that differential over expression of certain antiapoptotic proteins may account for the failure of curcumin to induce apoptosis in some cancer cells. Results from his laboratory suggest antiapoptotic roles for NF-κB, Bcl-XL and heat shock proteins such as hsp70 in curcumin-induced apoptosis. His laboratory has identified that NF-κB can also regulate epidermal growth factor-induced apoptosis by a similar mechanism.

Loss of transforming growth factor-β (TGF-β) sensitivity is observed in a wide variety of cancers including cervical cancer. His laboratory has reported a novel Smad 2 mutation in a human cervical tumor sample and loss of expression of Smad 2 and Smad 4 in different stages of cervical cancer progression and also the mutations of Smad 2 and Smad 4 in two of the six human cervical cancer cell lines analyzed revealing an important role for Smads in human cervical cancer for the first time.

Two of his research publications are now recognized as classic citations (more than 400 citations each) and two more have more than 200 citations each and his ‘h-index’ can be found in Google Scholar. For further details on current research interests, browse through the ongoing research projects.

Indian Institute of Technology, Madras
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Website updated 05-09-2013