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Last Updated: 9/5/2007
| Young E Whang, M.D., Ph.D.
Associate Professor of Medicine and Pathology |  |
Clinical Interests
I am a medical oncologist and my clinical interests are predominantly in genitourinary cancers. In particular, I am interested in developing novel targeted agents for treatment of prostate cancer. I am the Principal Investigator of several clinical trials of early and lates stages of prostate cancer, examining novel agents and chemotherapy in treatment of prostate cancer. I also care for patients with bladder and testicular cancer.
Research Interests
My laboratory is interested in characterizing the role of cytoplasmic signaling pathways in regulation of androgen receptor activity and progression of prostate cancer. Our studies have focused on HER-2 receptor tyrosine kinase and we have demonstrated that HER-2 activation stimulates androgen receptor activity and HER-2 inhibition inhibits androgen receptor transcriptional function at the level of recruitment to the androgen responsive enhancers. These findings have led to the design and initiation of the protocol involving lapatinib, a clinical HER-2 inhibitor, in treatment of patients with prostate cancer. More recently, we have demonstrated that activated Cdc42-associated kinase Ack1 promotes progression of prostate cancer via tyrosine phosphorylation of androgen receptor at Tyr-267 and Tyr-363 residues. We are interested in further characterizing the role of tyrosine phosphorylation of androgen receptor in prostate cancer and development of Ack1 targeted therapy for clinical use.
Recent Accomplishments and Honors
We have shown that tyrosine kinases HER-2 and Ack1 regulate androgen receptor activity in prostate cancer cells and mapped phosphorylation sites in androgen receptor.
We have designed and initiated a phase 2 clinical trial of lapatinib, the dual EGFR/HER-2 inhibitor, in patients with hormone refractory prostate cancer.
Honors and Awards
1999-Glaxo Wellcome Junior Faculty Award in Prostate Cancer Research
2000-Department of Defense Prostate Cancer Research Program New Investigator Award
2000-NIH K08 Physician Scientist Award
Training
Ph.D. 1988. University of Chicago
M.D. 1989. University of Chicago Pritzker School of Medicine
Internship and Residency in Internal Medicine. 1990-93. UCLA Medical Center
Fellowship in Hematology/Oncology. 1993-96. UCLA Medical Center
Board Certifications
Internal Medicine, 1993
Hematology, 1996
Medical Oncology, 1997
Publications
Yuan, X.J. and Whang, Y. (2002) PTEN sensitizes prostate cancer cells to death receptor-mediated and drug-induced apoptosis through a FADD-dependent pathway. Oncogene, 21, 319-327.
Mayo, M., Madrid, L., Westerheide, S., Jones, D., Yuan, X., Baldwin, A., and Whang, Y. (2002) PTEN blocks tumor necrosis factor-induced NF-kB-dependent transcription by inhibiting the transactivation potential of the p65 subunit. J. Biol. Chem., 277, 11116-11125.
Wu, W., Wang, X., Zhang, W., Reed, W., Samet, J., Whang, Y., and Ghio, A. (2003) Zinc-induced PTEN protein degradation through the proteasome pathway in human airway epithelial cells. J. Biol. Chem., 278, 28258-28263.
Nan, B., Snabboon, T., Unni, E., Yuan, X., Whang*, Y., and Marcelli*, M. (2003) The PTEN tumor suppressor is a negative modulator of androgen receptor transcriptional activity. J. Mol. Endocrin., 31, 169-183. *Contributed equally and considered co-senior authors.
Zhou, C., Gehrig, P., Whang*, Y., and Boggess, J. (2003) Rapamycin inhibits telomerase activity by decreasing the hTERT mRNA level in endometrial cancer cells. Mol. Cancer Therapeutics, 2, 789-795. *Corresponding Author.
Gregory, C., Whang, Y., McCall, W., Fei, X., Liu, Y., Ponguta, L., French, F., Wilson, E., and Earp, H. S. (2005) Heregulin-induced activation of HER2 and HER3 increases androgen receptor transactivation and CWR-R1 human recurrent prostate cancer cell growth. Clin. Cancer Res., 11, 1704-1712.
Liu, Y., Majumder, S., McCall, W., Sartor, C., Mohler, J., Gregory, C., Earp, H.S, and Whang, Y. (2005) Inhibition of HER-2/neu kinase impairs androgen receptor recruitment to the androgen responsive enhancer. Cancer Res., 65, 3404-3409.
Mahajan, N., Whang, Y., Mohler, J., and Earp, H.S. (2005) Activated tyrosine kinase Ack1 promotes prostate tumorigenesis: Role of Ack1 in polyubiquitination of tumor suppressor Wwox. Cancer Res., 65, 10514-10523.
Bae-Jump, V., Zhou, C., Gehrig, P., Whang, Y. and Boggess, J. (2006) Rapamycin inhibits hTERT telomerase mRNA expression, independent of cell cycle arrest. Gynecol. Oncol., 100, 487-494.
Zhou, C., Bae-Jump, V., Whang, Y., Gehrig, P., and Boggess, J. (2006) The PTEN tumor suppressor inhibits telomerase activity in endometrial cancer cells by decreasing the hTERT mRNA level. Gynecol. Oncol., 101, 305-310.
Majumder, S., Liu, Y., Harris, O. H., Mohler, J., and Whang, Y. (2006) Involvement of arginine methyltransferase CARM1 in androgen receptor function and prostate cancer viability. Prostate, 66, 1292-1301.
Hsiang, C., Tunoda, T., Whang, Y., Tyson, D., and Ornstein, D. (2006) The impact of altered annexin I protein levels on apoptosis and signal transduction pathways in prostate cancer cells. Prostate, 66, 1413-1424.
Boggess, J., Zhou, C., Bae-Jump, Gehrig, P., and Whang, Y. (2006) Estrogen receptor dependent regulation of telomerase activity in human endometrial cancer cell lines. Gynecol. Oncol., 103, 417-424.
Mahajan, N., Liu, Y., Majumder, S., Warren, M., Parker, C., Mohler, J., Earp, H. S., and Whang, Y. (2007) Activated Cdc42-associated kinase Ack1 promotes prostate cancer progression via androgen receptor tyrosine phosphorylation, Proc. Natl. Acad. Sci. USA, 104, 8438-8443.
E-mail: ywhang@med.unc.edu
Telephone: (919) 966-8645
FAX: (919) 966-8212
Address: Lineberger Comprehensive Cancer Center, Rm 22-016 CB# 7295 Chapel Hill, NC 27599-7295
