Stuart J. Frank, M.D. – Division Director

StuartFrankDivision 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

Physical Address:
1808 7th Avenue South, BDB 720
Birmingham, AL 35294-0012

Appointment Telephone: (205) 934-9877
Office Telephone: (205) 934-9877
Fax: (205) 934-4389

Training:
B.A., University of Pennsylvania, Philadelphia, PA. (summa cum laude), 1980
M.D., Harvard Medical School, Boston, MA, 1984

Residency:
Internal Medicine, Barnes Hospital, Department of Internal Medicine, Washington University School of Medicine, St.Louis, MO., 1984-87

Fellowship:
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

Certifications:
American Board of Internal Medicine
American Board of Internal Medicine/Endocrinology, Diabetes and Metabolism

Clinical Interests: General endocrinology, diabetes mellitus

Research Interests:
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.

Representative Publications:

  • 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.