Research Faculty Bio
A. Pratap Kumar, Ph.D.
Research Goals of the laboratory:
The long-term objective of my research program is to understand molecular and cellular mechanisms involved in development, progression and dissemination of prostate cancer using in vitro and in vivo pre-clinical animal models for potential translation to the bed side. Numerous cutting edge technologies including magnetic resonance imaging (to monitor in vivo tumor development), chromatin immunoprecipitations, gene and proteomic array along with functional assays are routinely used in the laboratory to achieve these goals. Accordingly one of the current projects is to understand the (i) signal transduction pathways (cis-elements and trans-factors) involved in the transcriptional activation of Cyclin D1, Cox-2, SIRT1 and FLIP and associated downstream cellular processes and (ii) mechanisms through which FLIP or Cox2-mediated resistance to apoptosis contributes to the development of hormone refractory prostate cancer (HRPCA). Another focus of our laboratory is to develop novel agents from natural products including curcumin, eugenol and resveratrol either alone or in combination that target such deregulated signaling pathways either to prevent or delay development and progression of prostate cancer.
Transcriptional regulation of FLIP during prostate carcinogenesis:
Studies from our laboratory identified a non-toxic estrogen metabolite namely 2-methoxyestradiol as an inhibitor of prostate tumor development in pre-clinical animal model that is associated with down regulation of FLIP. Studies also identified a critical role for transcription factor Sp1/Sp3 in the regulation of FLIP during prostate carcinogenesis (Clinical Cancer Research 2006 and 2009). Studies are in progress to investigate precise mechanism of FLIP de-regulation during development of hormone-refractory prostate cancer including the role of transcription factors and their interactions and microRNA’s.
Development of natural products for cancer management:
Studies from our laboratory identified NexrutineR, a bark extract from cork-tree (Phellodendron amurense) that inhibits prostate tumor development in a pre-clinical animal model. These studies further identified inhibition of transcriptional activation of Cox-2 through Akt mediated activation of CREB as a potential mechanism for the observed biological activities (Neoplasia, 2006 and 2007; Clinical Cancer Research 2007; The Prostate 2009; Anticancer Research 2010). Currently studies are in progress to develop NexrutineR as an agent for prostate cancer management either by itself or in combination with existing standard of care due to its ability to target Akt/mTOR signaling axis.
Studies are also in progress to develop NexrutineR for pancreatic cancer management specifically targeting EP receptor signaling.
Development of combinatorial approaches:
Studies are ongoing to understand the molecular events associated with development of metastatic prostate cancer to develop as targets for prostate cancer management using combination of agents.
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