Zafar Nawaz, Ph.D.
Senior Associate Dean, Office of Graduate & Postdoctoral Studies; Professor of Biochemistry & Molecular Biology; Associate Research Director, Braman Family Breast Cancer Institute at Sylvester
Description of Research
Dr. Nawaz's research focuses on mechanisms of steroid hormone receptor and coactivator action in normal, cancerous and nervous tissues, with important emphasis on estrogen receptor (ER) and androgen receptor (AR) regulation. Steroid hormones are important regulators of cell growth and influence cancer development as well as the nervous system organization and function, exerting biological effects on target tissues through intracellular receptor proteins. Coactivators positively influence steroid hormone receptor-mediated transcription. Dr. Nawaz was among the first to show that the ER is ubquitinated and that ligand binding activates rapid steroid hormone receptors proteolysis via the ubiquitin-proteasome pathway. For certain receptors, this is required for their proper functioning. He also demonstrated that an E3 ubiquitin-protein ligase enzyme named, E6-associated protein (E6-AP) and an E2 ubiquitin-conjugation enzyme, UbcH7, both act as coactivators of steroid hormone receptors. Dr. Nawaz is studying the role of E6-AP and UbcH7 in the regulation of steroid hormone receptors protein stability, steroid hormone receptor-dependent gene transactivation, breast and prostate carcinogenesis and central nervous system development. Additionally, Dr. Nawaz’s laboratory has also identified protein complexes consist of yes associated protein, WW domain-containing oxidoreductase and WW domain binding proteins (PY:WW domain complexes) as regulators of steroid hormone receptor signaling and breast tumorigenesis. Dr. Nawaz's laboratory has developed mammary gland specific transgenic mice, knockout mice, stable in vitro cell line models and other state of the art techniques to further its cutting edge scientific investigations.
- Discovered protein degradation is linked to steroid hormone receptor gene transcription
- Discovered novel proteins that regulate the functions of steroid hormone receptors, mammary gland and prostate gland development and tumorigenesis. These findings will be helpful in designing novel smart drugs for treatment of breast and prostate cancers.
- Developed novel cell and animal model systems for the study of breast and prostate cancers and of neurogenetic syndromes
- Fu W, Ma Q, Chen L, Li P, Zhang M, Ramamoorthy S, Nawaz Z, Shimojima T, Wang H, Yang Y, Shen Z, Zhang Y, Zhang X, Nicosia SV, Zhang Y, Pledger JW, Chen J, Bai W. MDM2 Acts Downstream of p53 as an E3 Ligase to Promote FOXO Ubiquitination and Degradation. J Biol Chem 284:13987-4000, 2009. Read more »
These discoveries, in addition to the ongoing leading edge research in the lab, will be helpful in designing novel smart drugs for treatment of breast and prostate cancers as well as numerous neurological diseases.
Selected Cancer-Related Publications
Collaborating in the Multidisciplinary Research Program(s):