Chawnshang Chang
George Hoyt Whipple Professor of Pathology & Laboratory Medicine, Oncology, and Urology
Ph.D. 1988 (University of Chicago)

Website:George Whipple Lab for Cancer Research

E-Mail: Chang@urmc.rochester.edu

      Since cloning androgen receptors (AR) (Science, 1988), finding the first AR coactivators (PNAS, 1996) and their linkage in prostate cancer (Lancet, 1997), and generation the first tissue- specific knockout AR mouse via cre-lox system (PNAS, 2002). Our laboratory has continued to focus on the study of molecular mechanisms of steroid hormone function, especially androgen action in prostate, testis, breast and brain. The lab goals are to study the physiological functions of AR in various target organs, to elucidate the mechanisms of how prostate cancer progresses from an androgen-dependant to an androgen-independent stage, and also develop the new antiandrogene without progression into antiandrogen withdrawal syndrome.The following summarizes our current AR research efforts from FIVE different directions:

1.	How does AR interact with transcriptional factors to regulate their target genes and how do other coregulators interact with AR to modulate target gene expression at the translation/transcription levels?
2.	Purification/crystallization of AR and AR coregulators and their use in screening antiandrogens.
3.	How can we identify T- or DHT-specific target genes and develop T- or DHT- specific antiandrogens?
4.	How can we clone AR-associated proteins and, from them, develop new types of antiandrogens by inhibiting the interaction of AR and ARAs?
5.	Generation and characterization of individual tissue-specific knockout mouse to study AR in vivo functions in (a) prostate/breast/liver/bladder cancers, (b) immune system, (c) male& female fertility, (d) baldness/acne and (e) brain-neuron.

For the orphan nuclear TR2/TR3/TR4 receptors that our Lab cloned, we will concentrate on the following topics:

1.	Identifying new ligands/hormones for TR2/TR3/TR4.
2.	Finding physiological roles of these ligands/hormones in proliferation, differentiation, and apoptosis.
3.	Studying the potential role of these ligands/hormones in resistance to radiation and chemo-therapeutic drugs
4.	Studying the bi-directional regulation between orphan receptors and (a) brain neuro-systems, (b) vitamin A and D systems, and (c) p53 tumor suppressors.
5.	Studying TR2/TR4 physiological roles in TR2/TR4 knock-out mice and in TR2/TR4-overexpressing transgenic mice.

In summary, by combining basic and clinical studies of androgen receptors and orphan nuclear receptors, we hope to develop a better understanding of androgen mechanisms and produce better antiandrogens leading to more effective drug therapies in the near future.

Ma WL, Hsu CL, Wu MH, Wu CT, Wu CC, Lai JJ, Jou YS, Chen CW, Yeh S, Chang C. Androgen Receptor Is a New Potential Therapeutic Target for the Treatment of Hepatocellular Carcinoma. Gastroenterology. 2008 May 22. [Epub ahead of print]

Ting HJ, Chang C. Actin associated proteins function as androgen receptor coregulators: An implication of androgen receptor's roles in skeletal muscle. J Steroid Biochem Mol Biol. 2008 Jun 11. [Epub ahead of print]

Lin HY, Yu IC, Wang RS, Chen YT, Liu NC, Altuwaijri S, Hsu CL, Ma WL, Jokinen J, Sparks JD, Yeh S, Chang C. Increased hepatic steatosis and insulin resistance in mice lacking hepatic androgen receptor. Hepatology. 2008 Jun;47(6):1924-1935.

Chen YT, Collins LL, Chang SS, Chang C. The roles of testicular orphan nuclear receptor 4 (TR4) in cerebellar development. Cerebellum. 2008 Mar 27. [Epub ahead of print]

Li G, Lee YF, Liu S, Cai Y, Xie S, Liu NC, Bao BY, Chen Z, Chang C. Oxidative stress stimulates testicular orphan receptor 4 through forkhead transcription factor forkhead box O3a. Endocrinology. 2008 Jul;149(7):3490-3499

Cai Y, Lee YF, Li G, Liu S, Bao BY, Huang J, Hsu CL, Chang C. A new prostate cancer therapeutic approach: combination of androgen ablation with COX-2 inhibitor. Int J Cancer. 2008 Jul 1;123(1):195-201.

Yu IC, Lin HY, Liu NC, Wang RS, Sparks JD, Yeh S, Chang C. Hyperleptinemia without obesity in male mice lacking androgen receptor in adipose tissue. Endocrinology. 2008 May;149(5):2361-2368.

Chen LM, Wang RS, Lee YF, Liu NC, Chang YJ, Wu CC, Xie S, Hung YC, Chang C. Subfertility with defective folliculogenesis in female mice lacking testicular orphan nuclear receptor 4. Mol Endocrinol. 2008 Apr;22(4):858-867.

Yeh, S., Miyamoto, H., Shima, H. and Chang, C. 1998. From estrogen to androgen receptor: a new pathway for sex hormone in human prostate. Proc. Natl. Acad. Sci. U S A , 95:5527-5532.

Chang, C., Kokontis, J., and Liao, S. 1988. Molecular cloning of human and rat complementary DNA encoding androgen receptors. Science, 240:324-326.