Stuart J. Frank, M.D. – Division Director
Professor of Medicine
Chief, Endocrinology Section, Birmingham VAMC Medical Service
Primary Appointment: Medicine / Endocrinology, Diabetes, and Metabolism
Secondary Appointments: Cell, Developmental and Integrative Biology
1808 7th Avenue South, BDB 720
Birmingham, AL 35294-0012
Appointment Telephone: (205) 934-9877
Office Telephone: (205) 934-9877
Fax: (205) 934-4389
B.A., University of Pennsylvania, Philadelphia, PA. (summa cum laude), 1980
M.D., Harvard Medical School, Boston, MA, 1984
Internal Medicine, Barnes Hospital, Department of Internal Medicine, Washington University School of Medicine, St.Louis, MO., 1984-87
Endocrinology and Metabolism, Developmental Endocrinology Branch, National Institute of Child Health and Human Development, NIH. Bethesda, MD. 1987-90
Medical Staff Fellow/Senior Staff Fellow, Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, NIH, Bethesda, MD. 1988-91
American Board of Internal Medicine
American Board of Internal Medicine/Endocrinology, Diabetes and Metabolism
Clinical Interests: General endocrinology, diabetes mellitus
The focus of research in my laboratory is understanding mechanisms of action of growth hormone (GH), an important metabolic and growth promoting hormone. In particular, I am interested in various aspects of GH receptor (GHR) structure and signal transduction. Our studies have examined the interaction of the GHR with a critical non-receptor cytoplasmic tyrosine kinase, JAK2, which is required for initiation of GHR signaling. We have explored the downstream signaling pathways (STAT, MAP kinase, and PI-3 kinase) activated by GH and their effects on GH-induced gene expression.
Our current interests surround several aspects of the actions of GH and prolactin. Specifically, we are intensely investigating: 1) molecular studies of mechanisms of GH-induced activation of the JAK2 tyrosine kinase; 2) the cellular determinants of sensitivity to GH and modulation of GHR availability and function; 3) inducible GHR metalloproteolysis as a mechanism of generation of the GH binding protein (GHBP) and as a regulator of in vivo hepatic GH sensitivity; 4) mechanisms of GH action in bone and muscle; 5) crosstalk between the GH and epidermal growth factor (EGF) signaling pathways, between the GH and insulin-like growth factor-1 (IGF-1) signaling pathways, and between the PRL and EGF signaling pathways.
In addition to these basic research activities, I have also taken on a leadership role in the realm of translational research. Since 2010, I have served as Co-Director (and co-PI) of the UAB Center for Clinical and Translational Science (CCTS; www.uab.edu/ccts/). The CCTS is UAB’s NIH-funded CTSA, an award that helps to fund this trans-institutional center with major efforts pertaining to clinical research resources, training and education, investigator services, and institutional research priorities. In my role, I assist the Director (Robert Kimberly, M.D.) in all aspects of the Center, focusing particularly on coordination of clinical services and clinical trials, the establishment and growth of a partnership network with institutions outside of UAB, and the development of novel programs to assist investigators in project design and implementation.
- Yang, N., Wang, X., Jiang, J., Frank, S.J. Role of the GH receptor transmembrane domain in receptor predimerization and GH-induced activation., Mol. Endocrinol., 21(7):1642-1655, 2007.
- Deng, L., He, K., Wang, X., Yang, N., Thangavel, C., Jiang, J., Fuchs, S.Y., Frank, S.J. Determinants of GH receptor downregulation., Mol. Endocrinol., 21(7):1537-1551, 2007.
- Asa, S.L., DiGiovanni, R., Jiang, J., Ward, M.L., Loesch, K., Yamada, S., Sano, T., Yoshimoto, K., Frank, S.J., Ezzat, S. A growth hormone receptor mutation impairs growth hormone autofeedback signaling in pituitary tumors. Cancer Research., 67(15): 7505-7511, 2007.
- Huang, Y., Li, X., Jiang, J., Frank, S.J. Prolactin modulates phosphorylation, signaling and trafficking of epidermal growth factor (EGF) receptor in human T47D breast cancer cells. Oncogene 25(58): 7565-7576, 2006.
- Frank, S.J., Wang, X., He, K., Yang, N., Fang, P., Rosenfeld, R.G., Hwa, V., Chaudhuri, T.R., Deng, L., Zinn, K.R. In vivo Imaging of Hepatic Growth Hormone Signaling. Mol. Endocrinol., 20(11): 2810-2830, 2006.
- Loesch, K., Deng, L., Cowan, J.W., Wang, X., He, K., Jiang, J., Black, R.A., Frank, S.J. JAK2 influences growth hormone receptor metalloproteolysis. Endocrinol., 147(6): 2839-2849, 2006.
- Cowan, J., Wang, X., Guan, R., He, K., Jiang, J., Baumann, G., Black, R.A., Wolfe, M.S., Frank, S.J. GH receptor is a target for both metalloprotease-mediated and ?-secretase cleavage. J. Biol. Chem., 280(19): 19331-19342, 2005.
- Jiang, J., Wang, X., He, K., Li, X., Chen, C., Sayeski, P.P., Waters, M.J., Frank, S.J. A conformationally-sensitive GHR (growth hormone (GH) receptor) antibody: impact on GH signaling and GHR proteolysis. Mol. Endocrinol., 18(12): 2981-2996, 2004.
- Huang, Y., Kim, S.-O., Yang, N., Jiang, J., Frank, S.J. Physical and functional interaction of GH and IGF-1 signaling elements. Mol. Endocrinol., 18(6): 1471-1485, 2004.
- He, K., Wang, X., Guan, R., Jiang, J., Bernstein, K.E., Sayeski, P.P., Frank, S.J. JAK2 determinants for growth hormone receptor association, surface assembly, and signaling. Mol. Endocrinol. 17(11): 2211-2227, 2003.
- Huang, H., Kim, S.-O., Jiang, J., Frank, S.J. GH-induced phosphorylation of EGF receptor in 3T3-F442A cells: modulation of EGF-induced signaling and trafficking. J. Biol. Chem., 278(21):18902-18913, 2003.
- Wang, X., He, K., Gerhart, M., Huang, Y., Jiang, J., Paxton, R.L., Yang, S., Lu, C., Menon, R.K., Black, R.A., Baumann, G., Frank, S.J. Metalloprotease-mediated GH receptor proteolysis and GHBP shedding: determination of extracellular domain stem region cleavage site., J. Biol. Chem., 277(52): 50510-50519, 2002.
- Guan, R., Zhang, Y., Jiang, J., Baumann, C.A., Black, R.A., Baumann, G., Frank, S.J. Phorbol ester- and growth factor-induced growth hormone receptor proteolysis and growth hormone binding protein shedding: relationship to growth hormone receptor downregulation. Endocrinology 142(3):1137-1147, 2001.
- Zhang, Y., Jiang, J., Black, R.A., Baumann, G., Frank, S.J. Tumor necrosis factor-alpha converting enzyme (TACE) is a growth hormone binding protein (GHBP) sheddase: the metalloprotease TACE/ADAM-17 is critical for (PMA-induced) growth hormone receptor proteolysis and GHBP generation. Endocrinology 141(12): 4342-4348, 2000.
- Kim, S.-O., Houtman, J., Jiang, J., Ruppert, J.M., Bertics, P.J., Frank, S.J. Growth hormone-induced alteration in ErbB-2 phosphorylation status in 3T3-F442A fibroblasts. J. Biol. Chem. 274 (50): 36015-36024, 1999.