Middle East Technical University Üniversiteler Mahallesi, Dumlupınar Bulvarı No:1 Biyolojik Bilimler, 118 06800 Çankaya Ankara/TURKEY

Office Room: 118

Tel: 0090 312 210 7653

Web: www.metu.edu.tr

Education: DVM, Ankara University Veterinary Faculty, 1980 PhD, Ankara University Health Sciences, 1987 PhD, University of California-Davis, 1991

Research Interest: Molecular Mechanism of the Estrogen-Estrogen Receptor Complex Signaling

Description of Research Activities: Our research interest is directed at the understanding of the molecular mechanisms of estrogen hormone action. The homeodynamic regulation of estrogen target tissue physiology relies on transient fluctuations in estrogen levels that are sensed by target organs that reply to hormone through a complex array of convergent and divergent signaling pathways. These pathways orchestrate cellular proliferation, differentiation and death that result in target tissue-specific responses. The flow of estrogen information is primarily conveyed by the transcription factors, estrogen receptors (ERs) α and β. The estrogen bound ERs mediate many nuclear and cytoplasmic events. One nuclear estrogen signaling involves the interaction of ERs with specific DNA sequences, estrogen responsive elements (EREs), of a target gene promoter. ERs subsequently recruits co-activators/regulators to initiate local chromatin remodeling and to bridge with general transcription factors for transcription. This pathway is called the ERE-dependent estrogen-ER signaling. Although ERs display similar biochemical functions, they differ in their mode of transcription in the ERE-dependent signaling pathway. ERs also regulate gene expression through functional interaction with transcription factors bound to their cognate regulatory element on DNA. This is the DNA-dependent and ERE-independent signaling pathway, which also responds to ERs differently. Furthermore, the membrane/cytoplasmic ERs can elicit distinct responses by associating with, and modifying the functions of, a variety of proximal signaling molecules. Utilizing a multidisciplinary approach that includes biochemistry, molecular, cellular, and tumor biology, one focus of our research is to address the underlying basis for the distinct transcription mode of ERs in order to provide a functional definition for the ERα and ERβ subtypes. We also focus on the dissection of estrogen signaling pathways to elucidate the relative importance of each pathway in physiology and pathophysiology of target tissue functions by using structurally modified ER subtypes and various in vitro and in situ experimental models. A better conceptualization of regulatory mechanisms for estrogen signaling is pivotally important for the understanding of the initiation and progression of estrogen target tissue malignancies that result from the uncoupling of regulatory mechanisms involved in cell proliferation and death. This recognition is providing us with an additional research focus that deals with the development of novel receptor-based modalities for the prevention and treatment of estrogen target tissue cancers.

Selected Publications: (Last five years) Huang Y, Li X, Muyan M (2011) Estrogen receptors similarly mediate the effects of 17beta-estradiol on cellular responses but differ in their potencies. Endocrine 39:48-61 Nott SN, Huang Y, Kalkanoglu A, Harper K, Chen M, Paoni S, Fenton B, Muyan M (2010) Designer Monotransregulators Provide a Basis for a Transcriptional Therapy for de novo Endocrine-Resistant Breast Cancer. Mol Medicine, 16:10-18 Nott SN, Huang Y, Li X, Fluharty B, Qui X, Welshons WV, Yeh S, Muyan M (2009) Genomic Responses from the Estrogen Responsive Element-Dependent Signaling Pathway Mediated by ERalpha are Required to Elicit Cellular Alterations. J Biol Chem. 284:15277-15288 Nott SN, Huang Y, Fluharty B, Sokolov A, Huang M, Cox C, Muyan M (2009) Do Estrogen Receptor-beta Polymorphisms play a role in Pharmacogenomics of Estrogen Signaling? Curr Pharmacogenomics Personalized Med, 6, 239-259 Chen M, Ni J, Chang HC, Lin CY, Muyan M, Yeh S. (2009) CCDC62/ERAP75 Functions as a Coactivator to Enhance Estrogen Receptor beta-Mediated Transactivation and Target Gene Expression in Prostate Cancer Cells. Carcinogenesis. 30:841-850 Chen, M, Ni J, Zhang, Y, Muyan M and Yeh S. (2008) ERAP75 functions as a coactivator to enhance estrogen receptor alpha transactivation in prostate stromal cells. Prostate. 68: 1273-1282. Li X, Nott SL, Huang Y, Hilf R, Bambara RA, Qui X, Yakovlev A, Welle S, Muyan M (2008) Gene expression profiling reveals that the regulation of ERE-independent genes by E2-ERbeta is uncoupled from the induction of phenotypic changes in cell models. J Mol Endocrinol 40: 211-229 Li, X, Huang J, Fluharty BR, Huang Y, Nott SL and Muyan, M (2008) What are comparative studies telling us about the mechanism of ERbeta action in the ERE-dependent E2 signaling pathway? J Steroid Biochem Mol Biol. 109: 266-272.

Graduate program affiliation: Molecular Biology and Genetics