 |
 |
|
 |
||
 |
 |
|
 |
|
|
Last Updated: 11/16/2009
| William Y Kim, M.D.
Assistant Professor of Medicine |  |
Clinical Interests
Renal Cell Carcinoma
Bladder Cancer
Prostate Cancer
Research Interests
My research explores the role of hypoxia-inducible factor (HIF) in tumorigenesis. HIF is a transcription factor that plays a key role in oxygen sensing and is critical for cellular adaptation to hypoxia and low pH both conditions known to characterize the tumor microenvironment. HIF has been demonstrated to be over expressed in the majority of solid tumors and has been correlated with poor prognosis and resistance to both radio and chemotherapy. These attributes make HIF a likely promoter of solid tumor growth, particularly as tumors outgrow their vascular supply and undergo a phenomenon termed the angiogenic switch. We have created and characterized a mouse model that will conditionally express a stabilized form of HIF, allowing us to spatially and temporally control its expression. With this mouse in hand we will characterize the effects of HIF over expression on the phenotype of several mouse models of human cancer (lung, pancreatic, and prostate).
Recent Accomplishments and Honors
2010 DOD Prostate Cancer Physician Research Training Award
2009 Damon Runyon Clinical Investigator Award
2008 Joan's Legacy Lung Cancer Foundation Award
2008 DOD Prostate Cancer New Investigator Award
2008 Melanoma Research Foundation Award
2004 NIH F32 (CA108314) Kirschstein NRSA Individual Fellowship (declined)
2004 NIH K08 (CA097203) Physician Scientist Training Award
2003 SPORE Renal Cell Carcinoma, Career Development Award
2002 ASCO Young Investigator Award
Training
2002-2005 Instructor in Medicine, Harvard Medical School, Boston, MA
1999-2002 Fellowship, Hematology and Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA
1996-1999 Internship and Residency, Internal Medicine, Beth Israel Hospital, Harvard Medical School, Boston, MA
1992-1996 M.D. Brown University Medical School
Publications
Kim WY, Whang YE, Pruthi RS, Baggstrom MQ, Rosenman JG, Wallen ES, Goyal LK, Grigson G, Watkins C, and Godley PA. Neoadjuvant Docetaxel / Estramustine Prior to Radical Prostatectomy or External Beam Radiotherapy in High Risk Localized Prostate Cancer: a Phase II Trial. Urol Oncol. In Press.
Pruthi RS, Nielsen M, Wallen EM, Rathmell WK, Godley P, Whang Y, Fielding F, Schultz H, Grigson G, and Kim WY. A phase II study of neoadjuvant erlotinib in patients with muscle-invasve bladder cancer undergoing radical cystectomy: clinical and pathological results. BJU Int. In Press.
Kim WY and Ivan M. Molecular responses to hypoxia: ancient pathways, clinical promises. J Cell Mol Med. In Press.
Kim WY*, Perera S*, Zhou B, Carretero J, Yeh JJ, Heathcote SA, Jackson AL, Nikolinakos P, Ospina B, Naumov G, Brandstetter KA, Weigman VJ, Zaghlul S, Hayes DN, Padera RF, Heymach JV, Kung A Sharpless NE, Kaelin WG, and Wong KK, HIF2α cooperates with RAS to promote lung tumorigenesis in mice. Journal of Clinical Investigation. 2009 Aug 119 (8), 2160-70.
Wang Y, Roche O, Yan MS, Finak G, Evans AJ, Metcalf JL, Hast BE, Hanna SC, Wondergem B, Furge KA, Irwin MS, Kim WY, Teh BT, Grinstein S, Park M, Marsden PA, and Ohh M, Regulation of endocytosis via the oxygen-sensing pathway. Nature Medicine. 2009 Mar;15(3):319-24.
Kim WY and Sharpless NE, VHL inactivation: a new road to senescence. Cancer Cell. 2008 Apr;13(4):295-7.
Hanna SC, Heathcote SA, and Kim WY, The mtor pathway in renal cell carcinoma. Expert Review in Anticancer Therapeutics. 2008 Feb;8(2):283-92.
Yang H, Minamishima YA, Yan Q, Schlisio S, Ebert BL, Zhang X, Zhang L, Kim WY, Olumi AF, and Kaelin WG, pVHL acts as an adaptor to promote the inhibitory phosphorylation of the NF-kB agonist card9 by ck2. Molecular Cell 2008, 28(1) Oct 12, 15-27.
Peterman KB, Rozenberg GI, Zedek D, Groben P, McKinnon K, Buehler C, Kim W, Shields JM, Penland S, Bear JE, Thomas NE, Serody J, Sharpless NE, Erk activation induces CD200 expression in melanoma. Journal of Clinical Investigation. 2007 Dec;117(12):3922-9.
Maynard M, Evans A, Shi W, Kim W, Lui FF, Ohh M, Dominant-negative HIF3alpha4 suppresses vhl-null renal cell carcinoma progression. Cell Cycle. 2007 Aug 26;6(22)
Irvin W, MacDonald G, Smith JK, Kim WY, Dexamethasone-induced posterior reversible encephalopathy syndrome. Journal of Clinical Oncology. 2007 Jun 10;25(17):2484-6.
Evans AJ, Russell RC, Roche O, Burry TN, Fish JE, Chow WK, Kim WY, Saravanan A, Maynard MA, Gervais ML, Sufan RI, Roberts AM, Wilson LA, Betten M, Vandewalle C, Berx G, Marsden PA, Irvin MS, The BT, Jewett MAS, Ohh M. VHL promotes e2 box-dependent e-cadherin transcription by hif-mediated regulation of sip1 and snail. Mol Cell Biol. 2007 Jan;27(1)157-69.Epub 2006
Kim WY and Sharpless NE. The regulation of ink4/arf in cancer and aging. Cell. 2006 Oct 20;127(2) 265-75.
Kim WY and Kaelin, WG. Molecular pathways in renal cell carcinoma - rationale for targeted treatment. Seminars in Oncology. 2006 Oct;33(5):588-95.
Kim WY, Safran M, Buckley RM, Ebert, BL, Glickman J, Bosenberg M, Regan M, Kaelin WG, Jr. Failure to prolyl hydroxylate hifa phenocopies vhl inactivation in vivo. EMBO Journal. 2006 Oct 4;25(19):4650-62.
Ji H, Li D, Chen L, Shimanmura T, Kobayashi S, McNamara K, Mahmood U, Mitchell A, Sun Y, Al-Hashem R, Chirieac LR, Padera R, Bronson RT, Kim W, Janne PA, Shapiro GI, Tenen D, Johnson BE, Weissleder R, Sharpless, NE, Wong KK. The impact of human EGFR kinase domain mutations on lung tumorigenesis and in vivo sensitivity to EGFR-targeted therapies.
Cancer Cell. 2006 Jun;9(6):485-95.
Safran M, Kim WY, O'Connell F, Flippin L, Gunzler V, Horner JW, DePinho RA, Kaelin WG Jr,. Mouse model for noninvasive imaging of HIF prolyl hydroxylase activity: assessment of an oral agent that stimulates erythropoietin production. Proc Natl Acad Sci USA. 2006 Jan 3;103(1): 105-10.
Kim, WY and Kaelin, WG. The role of VHL mutation in human cancer. Journal of Clinical Oncology. 2004 Dec;22(24): 4991-5004.
Kim, WY and Kaelin, WG. The von Hippel-Lindau tumor suppressor protein: new insights into oxygen sensing and cancer. Curr Opin Genet Dev. 2003 Feb;13(1):55-60.
Yang H, Ivan M, Min JH, Kim WY, Kaelin WG Jr., Analysis of von Hippel-Lindau Hereditary Cancer Syndrome: Implications of Oxygen Sensing. Methods in Enzymology, 2004; 381: 320-335.
Safran M, Kim WY, Kung A, Horner JW, DePinho RA, Kaelin WG. Mouse reporter strain of non-invasive bioluminescent imaging of cells that have undergone cre-mediated recombination. Mol Imaging 2003; 2(4): 297-302.
Kondo K, Kim WY, Lechpammer M, Kaelin WG Jr., Inhibition of hif2alpha is sufficient to suppress pvhl-defective tumor growth. PloS Biology 2003; 1(3): 439-444.
Ohh M, Kim WY, Moslehi JJ, Chen Y, Chau V, Read MA, Kaelin WG Jr. An intact nedd8 pathway is required for cullin-dependent ubiquitination in mammalian cells. EMBO Reports 2002; 3: 177-182.
Ivan M, Kondo K, Yang H, Kim W, Valiance J, Ohh M, Salic A, Arsara JM, Lane WS, Kaelin WG Jr. HIFalpha targeted for VHL-mediated destruction by proline hydroxylation: implications for O2 sensing. Science 2001; 292: 464-468.
E-mail: wykim@med.unc.edu
Telephone: 966-4765
FAX: 966-8212
Address: LCCC, 22-003 Chapel Hill, NC 27599
URL: cancer.unc.edu/kimlab
