My long-term career goal is to improve the quality of human life, including that of Veterans, through my research. My laboratory focuses on two broad and complimentary research areas: 1) cancer biology and 2) prevention and experimental therapeutics of cancer. My overall goal is to define the critical molecular and biochemical events that occur during cancer development that in turn will assist in identifying targets and new approaches and strategies for cancer management. While interested in cancer in general, my recent focus has been on skin and prostate cancers, both of which disproportionally affect the Veteran population. Examples of ongoing research in my laboratory are as follows. We are studying the role and functional significance of mitotic regulators, including the polo-like kinase (Plk) family of serine/threonine kinases, and how these factors interact with other important cell signaling pathways to influence cancer development and progression. In addition, we are trying to understand the role of nicotinamide adenine dinucleotide (NAD)+ -dependent deacetylases, namely the Sirtuin family proteins, in the development and/or progression of cancer. The second major focus of my research is to define the cancer chemopreventive/therapeutic potential of a variety of agents, such as resveratrol (a phytoalexin antioxidant found in grapes, nuts, berries and red wine), melatonin (the chief secretory product of the pineal gland and a known antioxidant), vitamin E (the major antioxidant in biomembranes) and selenium (an essential micronutrient for humans). My current VA-sponsored research focuses on identifying the mechanism of melanoma development and progression. This research area is extremely relevant to VA healthcare as the U.S. military engages in missions all over the world, including in the Middle East (Iraq and Afghanistan). Deployment to these regions results in significant UV irradiation exposure that increases the risk for malignant melanoma in the Veterans returning from these areas. Based on several studies, an increased incidence of melanoma was reported for World War II Veterans stationed in the Pacific and those exposed to dioxin-contaminated herbicides during Operation Ranch Hand in Vietnam. My ongoing research aims at defining the molecular mechanism of melanoma development. I believe that my research findings are moving towards the identification of novel strategies for the management of this deadly neoplasm. Thus, my work is relevant and significant to Veteran's healthcare and is in line with the mission of the Department of Veterans Affairs. The results of my research are published in a wide range of high-impact scientific journals. I have published more than 170 papers, 150 abstracts and several book chapters (Total Citations: 17,705; h-index, 65; i10-index: 1256 Source: Google Scholar; 8/2016). I serve as an Associate Editor of two well-respected journals, Toxicology and Applied Pharmacology and Photochemistry and Photobiology, and am a member of the Editorial Board of several other journals. I am regularly invited to participate in the peer-review of grants for national and international funding agencies, including the Department of Veterans Affairs, National Institutes of Health, and the Department of Defense. I am currently a regular member of the Radiation Therapeutics and Biology (RTB) Study Section of the NIH. I mentored numerous junior scientists at all levels (undergraduate, graduate, post-doctoral, and junior faculty). Many of my previous trainees/mentees have successfully obtained independent positions in academics and industry. In addition, I extensively collaborated with numerous scientists within the VA as well as at the University of Wisconsin, other universities in the U.S., and outside the country (internationally). I have always believed in the notion that `two heads are better than one'. A majority of my collaborations have been very successful, resulting in numerous papers and extramural funding. In summary, I believe that I am well qualified for the BLR&D Merit Review Research Career Scientist (RCS) Award, and I appreciate your consideration of my application.

Public Health Relevance

My current VA sponsored research focuses on identifying the mechanism of cancer development and progression. I have made high-impact research contributions that may have an impact on VA healthcare or advancing Veterans healthcare. I have an extensive record of successfully mentoring and training undergraduate and graduate students as well as post-doctoral fellows and early career scientists. Throughout my career, I have provided significant administrative service to local and national VA and non-VA research administration, by participating in various committees, study sections (VA, NIH, DOD, etc.), and on the editorial boards of many well-respected journals. I am routinely invited to give research talks/presentations at various institutes and scientific meetings. I have been invited to serve on organizing and scientific committees and to chair sessions at many scientific conferences. In addition, I have collaborated with VA and non-VA clinician scientists on various projects resulting in extramural grants and excellent peer-reviewed publications.

Agency
National Institute of Health (NIH)
Institute
Veterans Affairs (VA)
Project #
5IK6BX003780-02
Application #
9457157
Study Section
Research Career Scientist (RCSR)
Project Start
2017-04-01
Project End
2022-03-31
Budget Start
2018-04-01
Budget End
2019-03-31
Support Year
2
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Wm S. Middleton Memorial Veterans Hosp
Department
Type
DUNS #
086683091
City
Madison
State
WI
Country
United States
Zip Code
53705
Chhabra, Gagan; Garvey, Debra R; Singh, Chandra K et al. (2018) Effects and Mechanism of Nicotinamide Against UVA- and/or UVB-mediated DNA Damages in Normal Melanocytes. Photochem Photobiol :
Singh, Chandra K; Chhabra, Gagan; Ndiaye, Mary Ann et al. (2018) The Role of Sirtuins in Antioxidant and Redox Signaling. Antioxid Redox Signal 28:643-661
Denu, Ryan A; Shabbir, Maria; Nihal, Minakshi et al. (2018) Centriole Overduplication is the Predominant Mechanism Leading to Centrosome Amplification in Melanoma. Mol Cancer Res 16:517-527
Chhabra, Gagan; Singh, Chandra K; Ndiaye, Mary Ann et al. (2018) Prostate cancer chemoprevention by natural agents: Clinical evidence and potential implications. Cancer Lett 422:9-18
Wilking-Busch, Melissa J; Ndiaye, Mary A; Liu, Xiaoqi et al. (2018) RNA interference-mediated knockdown of SIRT1 and/or SIRT2 in melanoma: Identification of downstream targets by large-scale proteomics analysis. J Proteomics 170:99-109
Garcia-Peterson, Liz Mariely; Ndiaye, Mary Ann; Singh, Chandra K et al. (2017) SIRT6 histone deacetylase functions as a potential oncogene in human melanoma. Genes Cancer 8:701-712
Gutteridge, Rosie Elizabeth Ann; Singh, Chandra K; Ndiaye, Mary Ann et al. (2017) Targeted knockdown of polo-like kinase 1 alters metabolic regulation in melanoma. Cancer Lett 394:13-21
Cholewa, Brian D; Ndiaye, Mary A; Huang, Wei et al. (2017) Small molecule inhibition of polo-like kinase 1 by volasertib (BI 6727) causes significant melanoma growth delay and regression in vivo. Cancer Lett 385:179-187
Chhabra, Gagan; Ndiaye, Mary Ann; Garcia-Peterson, Liz Mariely et al. (2017) Melanoma Chemoprevention: Current Status and Future Prospects. Photochem Photobiol 93:975-989
Wilking-Busch, Melissa Jean; Ndiaye, Mary Ann; Huang, Wei et al. (2017) Expression profile of SIRT2 in human melanoma and implications for sirtuin-based chemotherapy. Cell Cycle 16:574-577

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