My Contact Information

Research Professor of Biochemistry and Biophysics, and Obstetric and Gynecology
D.V.M. Turkey-Ankara, Ankara Uni Fac Vet Med 1980
Ph.D. University of California at Davis 1991

Our research interest is to understand the molecular mechanisms of action of steroid hormone, estrogen. 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) a and b. The estrogen bound ERs mediate many nuclear and cytoplasmic events. One nuclear estrogen signaling involves the interaction of ERs with specific DNA sequences within gene promoters, known as estrogen responsive elements (EREs). ERs subsequently recruits co-activators/regulators to initiate local chromatin remodeling and to bridge with general transcription factors, thereby enabling gene 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 by tethering to a transcription factor bound to its cognate regulatory element on DNA. This is the DNA-dependent and ERE-independent signaling pathway that 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 basis for the distinct transcription mode of ERs in order to provide a functional characterization of the ERaand ERb subtypes. We also use structurally modified ER subtypes and various in vitro and in situexperimental models to focus on the dissection of estrogen signaling pathways to elucidate the relative importance of each pathway in physiology and pathophysiology of target tissue functions. A better conceptualization of regulatory mechanisms for estrogen signaling is pivotally important to understand 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.

Recent Publications

Chen M, Ni J, Zhang Y, Muyan M, Yeh S (2008) ERAP75 functions as a coactivator to enhance estrogen receptor alpha transactivation in prostate stromal cells. Prostate, 68:1273-82

Li X, Nott SL, Huang Y, Hilf R, Bambara RA, Qiu X, Yakovlev A, Welle S, Muyan M (2008) Gene expression profiling reveals that the regulation of estrogen-responsive element-independent genes by 17beta-estradiol-estrogen receptor beta is uncoupled from the induction of phenotypic changes in cell models. J Mol Endocrinol, 40:211-29

Li X, Huang J, Fluharty BR, Huang Y, Nott SL, 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,

Huang J, Li X, Qiao T, Bambara RA, Hilf R, Muyan M (2006) A tale of two estrogen receptors (ERs): how differential ER-estrogen responsive element interactions contribute to subtype-specific transcriptional responses. Nucl Recept Signal, 4:e015

Huang J, Li X, Hilf R, Bambara RA, Muyan M (2005) Molecular basis of therapeutic strategies for breast cancer. Curr Drug Targets Immune Endocr Metabol Disord, 5:379-96

Li X, Huang J, Yi P, Bambara RA, Hilf R, Muyan M (2004) Single-chain estrogen receptors (ERs) reveal that the ERalpha/beta heterodimer emulates functions of the ERalpha dimer in genomic estrogen signaling pathways. Mol Cell Biol, 24:7681-94

Huang J, Li X, Yi P, Hilf R, Bambara RA, Muyan M (2004) Targeting estrogen responsive elements (EREs): design of potent transactivators for ERE-containing genes. Mol Cell Endocrinol, 218:65-78

Sathya G, Yi P, Bhagat S, Bambara RA, Hilf R, Muyan M (2002) Structural regions of ERalpha critical for synergistic transcriptional responses contain co-factor interacting surfaces. Mol Cell Endocrinol, 192:171-85

Yi P, Bhagat S, Hilf R, Bambara RA, Muyan M (2002) Differences in the abilities of estrogen receptors to integrate activation functions are critical for subtype-specific transcriptional responses. Mol Endocrinol, 16:1810-27

Yi P, Driscoll MD, Huang J, Bhagat S, Hilf R, Bambara RA, Muyan M (2002) The effects of estrogen-responsive element- and ligand-induced structural changes on the recruitment of cofactors and transcriptional responses by ER alpha and ER beta. Mol Endocrinol, 16:674-93

Muyan M, Yi P, Sathya G, Willmert LJ, Driscoll MD, Hilf R, Bambara RA (2001) Fusion estrogen receptor proteins: toward the development of receptor-based agonists and antagonists. Mol Cell Endocrinol, 182:249-63

Cluster Affiliation    

Contact Information

E-Mail: mesut_muyan@urmc.rochester.edu

Mesut Muyan
Department of Biochemistry and Biophysics
University of Rochester School of Medicine and Dentistry
601 Elmwood Ave, Box 712
Rochester, New York 14642

Office: Medical Center 3-7537
Telephone: (585) 275-5613; Fax: (585) 275-6007