DEPARTMENT OF UROLOGY

A. Pratap Kumar, Ph.D.

  • A. Pratap Kumar, Ph.D.   photoA. Pratap Kumar, Ph.D.

    Professor

    Email: Kumara3@uthscsa.edu
    Telephone: 210-562-4116
    Fax: 210-562-4133

    Faculty Profile | Research Profile

     

    Education

    Ph.D., University of Hyderabad, India (1989)
    M.S., G. B. Pant University of Agriculture and Technology, India (1983)
    B.S (Hons)., Osmania University, Hyderabad, India (1980)

    Research

    While cancer deaths have dropped in the US, the human and financial cost of treatment has skyrocketed during this period. Therefore the old adage, 'prevention is better than cure' is the motto of our laboratory. We develop primary, secondary and tertiary chemoprevention approaches against cancer. To achieve this goal, we use a two-pronged approach- firstly we identify deregulated molecular mechanisms involved in development, progression and dissemination of cancer and secondly we develop chemoprevention/intervention strategies to target the identified mechanisms for clinical translation. To achieve these current research goals we use integrated approaches comprising of in vitro cell culture models and in vivo animal models including whole animal imaging, genomic and proteomics and validation studies using human tissues. Another important aspect of Dr Kumar's research program is to train and mentor next generation of cancer researchers.

    Project 1: High-grade prostate intraepithelial neoplastic lesions (HGPIN) are precursor lesions of prostate cancer. Since these lesions take decades to progress to clinical cancer, our efforts are focused on strategies to prevent the progression of HGPIN lesions. Anecdotal and epidemiological observations provide compelling evidence for beneficial effects of the calorie restriction mimetic resveratrol (RES) in preventing cardiovascular diseases and cancer. Our recently published work shows that RES intervention reduces the number of HGPIN lesions. A project to develop RES to prevent clinical prostate cancer by targeting HGPIN lesions via SIRT1-mediated autophagy is currently under investigation.

    Project 2: Androgen-independent prostate cancer is the most aggressive and less understood form of prostate cancer. There is a great need to find strategies to prevent progression to hormone-independent state. Ongoing efforts in our lab have led to the identification of a transcriptional network in androgen-independent prostate cancer as well as compounds that can be used as tools to target players involved in the network and prevent the development of this fatal form of prostate cancer.

    Project 3: Radiation therapy (RT) is an important modality of treatment for early, localized disease. RT is also associated with side effects such as radiation proctitis, rectal toxicity, impotence, gastro-intestinal bleeding and urinary dysfunction affecting quality of life. In addition, presence of radio-resistant cells is a major obstacle in successful treatment of PCA patients with radiotherapy. These observations underscore an unmet need to develop less toxic alternatives that (a) are safe and more effective in enhancing RT effects, (b) reduce side effects related to RT (c) prevent the progression and emergence of recurring cancer and (d) improve overall quality of life. Based on these lines of evidence, we focus on identifying compounds that can decrease the toxic effects of chemotherapy and/or radiotherapy. Along these lines we made a seminal discovery that Nexrutine, a Phellodendron amurense bark extract inhibits growth of prostate cancer cells in vitro and tumor growth in vivo. Subsequently, we tested whether Nexrutine synergizes with radiation so that lower doses of radiation can be used to decrease toxicity-associated side effects. We found that Nexrutine exhibits strong synergistic growth inhibitory activity in cell culture models. In addition, Nexrutine in combination with radiation showed remarkable effect in reducing the number of animals developing well differentiated tumors compared to radiation alone. Based on these exciting findings, we investigated the potential of Nexrutine in combination with radiation and surgery in prostate cancer patients. These results show Nexrutine is well tolerated with no grade 3 toxicity and 81% of patients showed decreased PSA during neo-adjuvant portion of the trial. Currently we are focusing on deciphering the underlying mechanisms associated with chemo-radioresistance to develop targeted approaches for effective management of PCA.

    Project 4: We are also developing biomarkers to distinguish indolent vs. aggressive prostate cancer. Identification of a panel of markers that can accurately predict aggressive disease will allow patient stratification and save men with sluggish disease the financial cost and mental agony of cancer diagnosis. Discoveries from our laboratory identified a combination of markers (patent pending) is an excellent predictor of biochemical recurrence. Ongoing studies are examining whether this biomarker signature can predict risk of aggressive disease in ethnic groups at high risk for prostate cancer.

    Project 5: Pancreatic cancer is a disease of near equal mortality. Current literature suggests that fibrosis may be an impediment for clinical management of pancreatic cancer patients. Our group has identified a potential role for transcription factor GLI and glutamine in mediating the interaction between pancreatic stellate cells (stroma) and pancreatic cancer cells in fibrosis development. On the translational side we are screening natural compounds that inhibit markers of fibrosis in vitro and a preclinical animal model of pancreatic cancer. Collaborative efforts with transplant surgeons at UTHSA/CTRC are focused on developing lead compounds in conjunction with conventional therapy for effective management of pancreatic cancer.

    Education outreach: An important goal of the Kumar laboratory is to ensure that we produce the best next generation of cancer prevention scientists. Students who have graduated from my laboratory are receiving additional training at prestigious institutions in the country including Sloan Kettering, Yale, Harvard, MD Anderson Cancer Center and industry.

    For post-doctoral or research assistant positions, please contact kumara3@uthscsa.edu

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