Dr. Sun's experience in the fields of cancer biology, DNA chemistry, transcriptional regulation, G-quadruplex biology, drug screening via cell-based high throughput assay, and medicinal chemistry has helped him greatly in building his professional career in cancer research areas and qualifies me for the work proposed in this application.
As a PI or co-Investigator on several previous and ongoing state-, NIH-, and privately funded grants, Dr. Sun has successfully administered projects (e.g. staffing, research protections, budget) individually and produced several peer-reviewed publications. As a PI in prior R01 grants, he has contributed to research projects exploring the VEGF G-quadruplex as a potential target for antiangiogenic agents. His publications have also documented the importance of G-quadruplex structures in the transcriptional regulation of human oncogenes.
Dr. Sun's current, ongoing project is to explore a new therapeutic strategy to blunt the effect of mutations in the RET proto-oncogene in human MTC, a tumor type characterized by germline RET point mutations. In particular, he is investigating the use of small molecules (anti-RET agents) to specifically inhibit RET transcriptional activation and ultimately hope to directly evaluate the antitumor effects of anti-RET agents in a preclinical model of human MTC. This experience in G-quadruplex biology as well as in his ongoing project form the technical and scientific basis for his current application. In summary, as a member of the University of Arizona Cancer Center (UACC), Dr. Sun has the expertise, leadership, and motivation necessary to successfully carry out his role in continuing his collaboration with researchers at the UACC.
Dr. Sun’s research activities are directed toward discovering new agents that are more selective for cancer cells than normal cells with novel mechanisms of action, elucidating the mechanisms of action of novel natural products with antineoplastic activity, and understanding drug resistance mechanisms in human cancer cells to anticancer drugs.
Dr. Sun is also involved in teaching Medicinal Chemistry for professional Pharmacy students as well as graduate students from different disciplines.
- Shin YJ, Kumarasamy V, Camacho D, Sun D. Involvement of G-quadruplex structures in regulation of human RET gene expression by small molecules in human medullary thyroid carcinoma TT cells. Oncogene 2014 Mar 24 [Epub ahead of print].
- Kumarasamy VM, Sun D (2013) Current and Future Views in G-Quadruplex Secondary Structure as an Anti-Cancer Target. J Phys Chem Biophys 3: e117 (2013).
- Uribe DJ, Shin YJ, Lau E, Ebbinghaus SW, Sun D. Heterogeneous nuclear ribonucleoprotein K binds to the cytosine-rich sequence of the hypoxia inducible factor 1 alpha proximal promoter that forms a stable i-motif at neutral pH. J Phys Chem Biophys S5: 001 (2013).
- Keerthi K, Rajapakse A, Sun D, Gates KS. Synthesis and characterization of a small analogue of the anticancer natural product leinamycin. Bioorg Med Chem 21(1):235-41 (2013).
- Viswesh V, Hays AM, Gates K, Sun D. DNA cleavage induced by antitumor antibiotic leinamycin and its biological consequences. Bioorg Med Chem 20:4413-21 (2012).
- Sivaramakrishnan S, Breydo L, Sun D, Gates KS. The macrocycle of leinamycin imparts hydrolytic stability to the thiol-sensing 1,2-dithiolan-3-one 1-oxide unit of the natural product. Bioorg Med Chem Lett 22:3791-4 (2012).
- Sinha P, Shin Y, Hays AM, Gates K, Sun D. Cellular responses to the DNA damaging natural compound leinamycin. J Cancer Sci Ther S8:003 (2012).
- Sun D, Guo K, Shin YJ. Evidence of the formation of G-quadruplex structures in the promoter region of the human vascular endothelial growth factor gene. Nucleic Acids Res 39:1256-65 (2011).
- Uribe DJ, Guo K, Shin YJ, Sun D. Heterogeneous nuclear ribonucleoprotein K and nucleolin as transcriptional activators of the vascular endothelial growth factor promoter through interaction with secondary DNA structures. Biochemistry 50:3796-806 (2011).
- Viswesh V, Gates K, Sun D. Characterization of DNA damage induced by a natural product antitumor antibiotic leinamycin in human cancer cells. Chem Res Toxicol 23(1):99-107 (2010).
- Sun D, Hurley LH. Biochemical techniques for the characterization of G-quadruplex structures: EMSA, DMS footprinting, and DNA polymerase stop assay. Methods Mol Biol 608:65-79 (2010).
- Sun D. In vitro footprinting of promoter regions within supercoiled plasmid DNA. Methods Mol Biol 613:223-33 (2010).
- Sun D, Melman G, LeTourneau NJ, Hays AM, Melman M.. Synthesis and antiproliferating activity of the iron chelators of the hydroxyamino-1, 3, 5-triazine family. Bioorg Med Chem Lett 20:2458-460 (2010).
- Zheng J, Liu X, Yuan Q, Shin YJ, Sun D, Lu Y. Thiol-dependent DNA cleavage by aminomethylated Beaucage’s reagent. Org Biomol Chem 8:1293-5 (2010).
Active Member of American Association of Cancer Research (1995-Present)
Active Member of American Chemical Society (2009-Present)
Active Member, Southern Arizona section of the American Chemical Society (2013-present)
2008-2014 Assistant Professor, Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, Tucson, Arizona
2002-2008 Associate Research Scientist, Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, Tucson, Arizona
1998-2002 Assistant member, Institute for Drug Development, Cancer Therapy & Research Center, San Antonio, Texas
1995-1998 Research Scientist, Institute for Drug Development, Cancer Therapy & Research Center, San Antonio, Texas