Jaideep Thottassery, Ph.D.

Biography

Dr. Thottassery obtained his Ph.D. from the School of Biological Sciences at The University of Missouri-Kansas City and subsequently completed a postdoctoral fellowship at St. Jude Children's Research Hospital, Memphis, TN where he worked on the regulation of multi-drug resistance genes by p53, steroid receptors and other transcription factors. At Southern Research Dr. Thottassery has been involved in cancer therapeutics and breast cancer related areas. Dr. Thottassery has received a Susan G. Komen Breast Cancer Foundation grant for the development and characterization of a bitransgenic mouse model of mammary tumorigenesis and a Career Development Grant from the UAB Breast SPORE for the development of estrogen receptor positive mammary metastasis models. Dr. Thottassery is also an adjunct graduate faculty member at the UAB School of Medicine Department of Pathology and a member of the UAB Comprehensive Cancer Center.

Research Interests

There are two main areas of research in this laboratory. One interest is to elucidate mechanisms of antiestrogen resistance in breast cancer patients. In the two-thirds of breast cancer patients that have estrogen receptor positive (ER +ve) disease, estrogen has a critical role in the growth of tumor cells. Tamoxifen, an ER agonist/antagonist, has remained the mainstay of treatment in ER +ve disease, although progression after an initial response remains a significant problem. ICI 182780 (Faslodex), a pure antiestrogen, inhibits the growth of tamoxifen-resistant lines and also has shown effectiveness in tamoxifen-resistant patients, although there were no complete responses. Research in Dr. Thottassery's laboratory seeks to understand the mechanisms of antiestrogen resistance, which could lead to strategies that might either restore or prolong sensitivity to such therapies. Studies in this laboratory have demonstrated that Cks1, a small protein component of cyclin-cdk complexes, which is also a part of the SCF^Skp2 ubiquitin ligase, contributes to multiple essential roles during cell cycle progression in ER+ breast cancer cells (Westbrook et al Cancer Research 67:11393-401, 2007). These studies showed that Cks1 was essential for cycling induced by either estradiol or growth factors that stimulate antiestrogen-resistant growth like heregulin β1. Cks1 depleted cells not only exhibit slowed G1 progression, but also accumulate in G2/M due to blocked mitotic entry as a result of diminished cdk1 expression. This suggests that Cks1 plays certain non-redundant roles in these proliferative pathways in breast cancer cells and therefore can be a target for therapy in addition to adjuvant antiestrogens.

Another interest of this laboratory is to understand the molecular mechanisms whereby newer nucleosides that are being synthesized at Southern Research, and ones currently employed in the clinic, elicit their effects, and to determine whether modulation of cellular pathways can alter the sensitivity of tumors to these compounds.