The main objective of this application is to seek full support for me to become an independent investigator in the field of cancer prevention. Two primary goals are: (1) to establish my career as an independent researcher in the field of cancer prevention, and (2) to make a research contribution in developing useful new agents for chemoprevention, based on understanding their mechanisms of action. My short-term goals involve the design of new agents, studying mechanisms of action of these new agents, and investigating new agents in preclinical studies. Collaborators from Dartmouth Medical School, Dartmouth College, and Norris Cotton Cancer Center, as well as a distinguished group of consultants, will help me to widen the breadth and increase the depth of my knowledge in the field of cancer prevention areas as diverse as organic chemistry, advanced molecular biology, pathology, and clinical study design. The immediate research plan proposed here has three Specific Aims: 1) to elucidate structure-activity relationships of new synthetic triterpenoids in my molecular biology laboratory; 2) to study molecular and cellular mechanisms of action of new chemopreventive agents. Based on preliminary studies with triterpenoids, specific molecular targets will be investigated as follows: inflammatory genes such as iNOS and COX-2, specific nuclear receptors, such as PPAR-gamma and its associated co-activators and co-repressors, and the TGF-beta receptor and Smad signaling system; and 3) to evaluate new chemopreventive agents in animal models relevant to human disease. Such studies will lead to the most effective clinical translation of my work. New chemopreventive agents will be tested in two models of breast cancer, namely ER positive (NMU-induced breast cancer model in rats) and ER negative (a transgenic mouse model), as well as the azoxymethane-induced colon cancer model in rats. Thus, the short-term goal of my research is to develop new chemopreventive agents whose use can be clinically validated. My long-term goal is to become an independent investigator who can contribute to the entire process of making basic scientific knowledge effective in preventing cancer in men and women.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Career Transition Award (K22)
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Study Section
Subcommittee G - Education (NCI)
Program Officer
Eckstein, David J
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Rutgers University
Schools of Pharmacy
New Brunswick
United States
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Suh, Nanjoo; Paul, Shiby; Lee, Hong Jin et al. (2007) Mixed tocopherols inhibit N-methyl-N-nitrosourea-induced mammary tumor growth in rats. Nutr Cancer 59:76-81
Lee, Hong Jin; Ji, Yan; Paul, Shiby et al. (2007) Activation of bone morphogenetic protein signaling by a Gemini vitamin D3 analogue is mediated by Ras/protein kinase C alpha. Cancer Res 67:11840-7
Suh, Nanjoo; Paul, Shiby; Hao, Xingpei et al. (2007) Pterostilbene, an active constituent of blueberries, suppresses aberrant crypt foci formation in the azoxymethane-induced colon carcinogenesis model in rats. Clin Cancer Res 13:350-5
Lee, Hong Jin; Wislocki, Andrew; Goodman, Catherine et al. (2006) A novel vitamin D derivative activates bone morphogenetic protein signaling in MCF10 breast epithelial cells. Mol Pharmacol 69:1840-8
Liby, Karen; Rendi, Mara; Suh, Nanjoo et al. (2006) The combination of the rexinoid, LG100268, and a selective estrogen receptor modulator, either arzoxifene or acolbifene, synergizes in the prevention and treatment of mammary tumors in an estrogen receptor-negative model of breast cancer. Clin Cancer Res 12:5902-9
Ji, Yan; Lee, Hong Jin; Goodman, Catherine et al. (2006) The synthetic triterpenoid CDDO-imidazolide induces monocytic differentiation by activating the Smad and ERK signaling pathways in HL60 leukemia cells. Mol Cancer Ther 5:1452-8
Banach-Petrosky, Whitney; Ouyang, Xuesong; Gao, Hui et al. (2006) Vitamin D inhibits the formation of prostatic intraepithelial neoplasia in Nkx3.1;Pten mutant mice. Clin Cancer Res 12:5895-901
Lee, Hong Jin; Liu, Hao; Goodman, Catherine et al. (2006) Gene expression profiling changes induced by a novel Gemini Vitamin D derivative during the progression of breast cancer. Biochem Pharmacol 72:332-43
Liby, Karen; Hock, Thomas; Yore, Mark M et al. (2005) The synthetic triterpenoids, CDDO and CDDO-imidazolide, are potent inducers of heme oxygenase-1 and Nrf2/ARE signaling. Cancer Res 65:4789-98