Uddhav P. Kelavkar, PhD
Assistant Professor
Maharaja Sayajirao University of Baroda, India, 1993
Email: kelavkarup@upmc.edu
Research Interests:
Americans now consume substantially more processed plant fats and oils as compared with animal fats, and studies indicate that this high-fat diet likely plays a role in an increased risk for prostate cancer (PCa). Ideally, the ratio of omega (n)-3 to n-6 fatty acids should be 1-4:1, but many Americans ingest 10 to 20 times more n-6 than n-3 fatty acids, leading to an imbalanced ratio and higher cancer incidence of PCa. PCa remains the second most commonly diagnosed cancer in American men, with over 230,000 new cases predicted for 2005 alone. Specifically, consumption of omega (n)-6 polyunsaturated fatty acids (PUFAs), such as linoleic acid (LA) and arachidonic acid (AA) from plant oils, correlates with increased risk whereas consumption of n-3 fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) found in fish oils, correlates with decreased risk. With the "baby boomer" generation approaching the target age for PCa screening, this number is expected to rise precipitously to 300,000 unless major advances in prevention become available. Treatment options depend largely on the stage of the disease, the age and health of the patient, as well as whether the cancer has just been diagnosed or has recurred. Unfortunately though, many of these treatments can negatively impact the quality of life. Moreover, every year approximately 70,000 men present with recurrent disease and no curative therapy exists for advanced metastatic PCa. Given the long latency period for PCa progression along with the close association between aging and disease incidence, therapies that impede growth would make PCa clinically irrelevant. Thus, a major goal of our laboratory has been to identify key events that can be pro-actively targeted to slow PCa development. Our laboratory is studying the roles of polyunsaturated omega-6 fatty acid metabolism in PCa initiation and progression, particularly an enzyme called 15-lipoxygenase-1, using animal models and cell lines including a recently generated transgenic mouse model of prostate neoplasia. Other areas of interest are bladder cancer, epigenetics and molecular profiling.
Recent Publication
Kelavkar UP, Hutzley J, Dhir R, Kim P, Allen K, McHugh K (2006). Prostate tumor growth and recurrence can be modulated by the omega (¦Ø)-6: ¦Ø-3 ratio in diet: Athymic mouse xenograft model simulating radical prostatectomy. Neoplasia, 8: 112-124.
Kelavkar UP, Lin Y, Landsittel D, Chandran U, Dhir R (2006). The Yin and Yang of 15-lipoxygenase-1 and Delta-5-desaturase: Dietary omega-6 Linoleic acid metabolic pathway in prostate carcinogenesis. Journal of Carcinogenesis, 5:9.
Kelavkar UP, Parwani A, Shappell S, Martin W (2006). Conditional expression of human 15-lipoxygenase-1 in adult mouse prostate induces prostatic intraepithelial neoplasia: the FLiMP mouse model. Neoplasia, 8: 510-522.
Sen M, McHugh K, Dhir R, Hutzley J, Philips B, Parwani A, Kelavkar UP (2006). Forced overexpression of human 15-lipoxygenase (LO)-1, in the prostate of normal wild-type C57BL/6 mouse, causes neoplasia. Prostaglandins & other Lipid Mediators, 81: 1-13.
Kelavkar UP, Harya N, Hutzley J, Bacich DJ, Monzon FA, Chandran U, Dhir R and O¡¯Keefe DS (2007). DNA methylation paradigm shift: 15-lipoxygenase-1 upregulation in prostatic intraepithelial neoplasia and prostate cancer by atypical promoter hypermethylation. Prostaglandins & other Lipid Mediators, 82: 185-197.
Philips B, Hutzley J, Dhir R, Sen M, Kelavkar UP (2007). 15-Lipoxygenase-1 expression in normal and cancerous human bladder. Applied Immunohistochemistry & Molecular Morphology, In Press.
