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Faculty Detail    
Name STUART J FRANK
  
Campus Address FOT 1224 Zip 0000
Phone  (205) 934-9877
E-mail  sjfrank@uab.edu
Other websites Stuart Frank
     

Education
Undergraduate  University of Pennsylvania    1980  B.A. 
Medical School  Harvard Medical School     1984  Medical 
Residency  Barnes Hospital, Department of Internal Medicine,    1987  Residency 
Residency  Washington University School of Medicine    1987  Residency 
Fellowship  Endocrinology and Metabolism, Developmental Endocrinology Branch, National Institute of Child Health and Human Development    1990  Fellowship 
Fellowship  Medical Staff Fellow/Senior Staff Fellow. Cell Biology and Metabolism Branch, NICHD, National Institutes of Health, Bethesda, MD.     1991  Fellowship 


Faculty Appointment(s)
Appointment Type Department Division Rank
Primary  Med - Endocrinology, Diabetes & Metabolism  Med - Endocrinology, Diabetes & Metabolism Professor Emeritus

Graduate Biomedical Sciences Affiliations
Biochemistry and Structural Biology 
Cancer Biology 
Cell, Molecular, & Developmental Biology 
Cellular and Molecular Biology Program 
Hughes Med-Grad Fellowship Program 
Integrative Biomedical Sciences 
Medical Scientist Training Program 
Pathobiology and Molecular Medicine 
Waiting to be Seated 

Biographical Sketch 
Stuart J. Frank (b. 1958, Wilkes-Barre, PA), Professor of Medicine, Cell Biology, and Physiology, received his B.A. summa cum laude in 1980 as a Benjamin Franklin Scholar at the University of Pennsylvania. He earned his M.D. in 1984 from Harvard Medical School. After residency in Internal Medicine at Washington University in St. Louis, Dr. Frank began fellowship training at the National Institutes of health from 1987 to 1991. His research there in Dr. Richard Klausner’s laboratory focused on T-cell antigen receptor signal transduction. Dr. Frank has been a UAB faculty member since 1991 in the Division of Endocrinology and Metabolism in the Department of Medicine, where his studies are aimed at understanding growth hormone (GH) receptor signal transduction and structure/function relationships and mechanisms of generation of the GH binding protein. He is also Chief of the Endocrinology Section in the Medical Service at the Birmingham Veterans Affairs Medical Center. His research is supported by grants from NIH and the Department of Veterans Affairs.

Society Memberships
Organization Name Position Held Org Link
AAAS  Member   
Endocrine Society  Member   
Massachusetts Medical Society  Member   
Southern Society for Clinical Investigation  Member   
 



Research/Clinical Interest
Title
Growth Hormone Action and GH Receptor Structure and Function
Description
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. Further, we are interested in the cellular determinants of sensitivity to GH and modulation of GHR availability and function. Current efforts include: 1) molecular studies of mechanisms of GH-induced activation of the JAK2 tyrosine kinase and the role of JAK2 in GHR stability and trafficking; 2) studies of mechanisms of generation of GH binding protein (GHBP), the shed extracellular domain of the GHR found in the circulation of humans, rabbits, and rodents that may modulate GH signaling; 3) studies of the role of a GH-induced disulfide-linked form of the GHR in signaling and receptor trafficking; 4) crosstalk between the GH and epidermal growth factor (EGF) signaling pathways, particularly EGF receptor and the oncogene, ErbB-2; and 5) crosstalk between the GH and insulin-like growth factor-1 (IGF-1) signaling systems. Multiple techniques including molecular and cell biological and protein chemistry approaches are being employed to achieve these goals.

Selected Publications 
Publication PUBMEDID
Alele, J., Jiang, J., Goldsmith, J.F., Yang, X., Maheshwari, H.G., Black, R.A., Baumann, G., Frank, S.J. Blockade of Growth Hormone Receptor Shedding by a Metalloprotease Inhibitor. Endocrinology 139 (4): 1927-1935, 1998.  9528979 
Kim, S.-O., Jiang, J., Yi, W., Feng, G.-S., Frank, S.J. Involvement of the SH2-containing Tyrosine Phosphatase SHP-2 in Growth Hormone Signalling. J. Biol. Chem. 273(4): 2344-2354, 1998.  9442080 
Wang, X., Cowan, J.W., Gerhart, M., Zelickson, B.R., Jiang, J., He, K., Wolfe, M.S., Black, R.A., Frank, S.J. gamma-Secretase-mediated growth hormone receptor proteolysis: mapping of the intramembranous cleavage site. Bioch. Biophys. Res. Comm. 408(3): 432-436, 2011  21514282 
Xu, J., Zhang, Y., Berry, P.A., Jiang, J., Lobie, P.E., Langenheim J.F., Chen, W.Y., Frank, S.J. Growth hormone signaling in human T47D breast cancer cells: potential role for a growth hormone receptor-prolactin receptor complex. Mol. Endocrinol. 25(4): 597-610, 2011.  21310852 
Li, X., Huang, Y., Jiang, J., Frank, S.J. Synergy in ERK activation by cytokine receptors and tyrosine kinase growth factor receptors. Cellular Signalling, 23(2):417-424, 2011.  20946955 
Mavalli, M.D., DiGirolamo, D.J., Riddle, R.C., Fan, Y., Campbell, K.S., Sperling, M.A., van Groen, T., Frank, S.J., Bamman, M.M., Clemens, T.L. Distinct growth hormone receptor signaling modes control skeletal muscle development and insulin sensitivity. J. Clin. Invest., 120(11): 4007-4020, 2010.   20921627 
Gan, Y., Zhang, Y., DiGirolamo, D., Jiang, J., Wang, X., Cao, X., Zinn, K.R., Carbone, D.P., Clemens, T.L., Frank, S.J. Deletion of Insulin-like Growth Factor-1 Receptor (IGF-1R) in primary osteoblasts reduces GH-induced STAT5 signaling. Mol. Endocrinol. 24(3): 644-656, 2010.   20133448 
Yang, N., Jiang, J., Deng, L., Waters, M.J., Wang, X., Frank, S.J. Growth hormone receptor targeting to lipid rafts requires extracellular subdomain 2. Bioch. Biophys. Res. Comm., 391(1): 414-418, 2010.   19914217 
Wang, X., Yang, N., Deng, L., Li, X., Jiang, J., Gan, Y., Frank, S.J. Interruption of growth hormone signaling via SHC and ERK in 3T3-F442A preadipocytes upon knockdown of insulin receptor substrate-1. Mol. Endocrinol. 23(4): 486-496, 2009.   19164446 
Li, X., Huang, Y., Jiang, J., Frank, S.J. ERK-mediated threonine phosphorylation of EGF receptor: impact on receptor downregulation and signaling. Cellular Signalling, 20(11):2145-2155, 2008.  18762250 
Wang, X., Jiang, J., Warram, J., Baumann, G., Gan, Y., Menon, R.K., Denson, L.A., Zinn, K.R., Frank, S.J. Endotoxin-induced proteolytic reduction in hepatic growth hormone (GH) receptor: a novel mechanism for GH insensitivity. Mol. Endocrinol., 22(6):1427-1437, 2008.  18323468 
Frank, S.J. Mechanistic Aspects of Crosstalk Between GH and PRL and ErbB Receptor Family Signaling. J Mammary Gland Biol Neoplasia 13(1):119-29, 2008  18236142 
Zinn, K.R., Chaudhuri, T.R., Szafran, A.A., O'Quinn, D., Weaver, C., Dugger, K., Lamar, D., Kesterson, R.A., Wang, X., Frank, S.J. Noninvasive bioluminescence imaging in small animals. ILAR J: 49(1):103-15, 2008  18172337 
Yang, N., Langenheim, J.F., Wang, X., Jiang, J., Chen, W.Y., Frank, S.J. Activation of growth hormone receptors by growth hormone and growth hormone antagonist dimers: insights into receptor triggering. Mol Endocrinol 22(4):978-88, 2008.   18096690 
Loesch, K., Deng, L., Wang, X., He, K., Jiang, J., Frank, S.J. Endoplasmic reticulum-associated degradation of growth hormone receptor in Janus kinase 2-deficient cells. Endocrinology 148(12):5955-65, 2007.  17761766  
DiGirolamo, D.J., Mukherjee, A., Fulzele, K., Gan, Y., Cao, X., Frank, S.J., Clemens, T.L. Mode of growth hormone action in osteoblasts.J Biol Chem. 2007 Oct 26;282(43):31666-74  17698843 
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 Res. 2007 Aug 1;67(15):7505-11.  17671221  
Deng, L., He, K., Wang, X., Yang, N., Thangavel, C., Jiang, J., Fuchs, S.Y., Frank, S.J. Determinants of growth hormone receptor down-regulation. Mol Endocrinol. 2007 Jul;21(7):1537-51.   17488973 
Yang, N., Wang, X., Jiang, J., Frank, S.J. Role of the growth hormone (GH) receptor transmembrane domain in receptor predimerization and GH-induced activation. Mol Endocrinol. 2007 Jul;21(7):1642-55.  17456794  
Frank, S.J. Growth hormone, insulin-like growth factor I, and growth: local knowledge. Endocrinology. 2007 Apr;148(4):1486-8.   17369499 
Frank SJ, Wang X, He K, Yang N, Fang P, Rosenfeld RG, Hwa V, Chaudhuri TR, Deng L, Zinn KR. In vivo Imaging of Hepatic Growth Hormone Signaling.
Mol Endocrinol. 2006 Nov;20(11):2819-30.  		 16803867 
Huang Y, Li X, Jiang J, Frank SJ. Prolactin modulates phosphorylation, signaling and trafficking of epidermal growth factor receptor in human T47D breast cancer cells.
Oncogene. 2006 Dec 7;25(58):7565-76. 		 16785991  
Loesch K, Deng L, Cowan JW, Wang X, He K, Jiang J, Black RA, Frank SJ. Janus kinase 2 influences growth hormone receptor metalloproteolysis. Endocrinology. 2006 Jun;147(6):2839-49.
 		 16497804 
He K, Loesch K, Cowan JW, Li X, Deng L, Wang X, Jiang J, Frank SJ. Janus kinase 2 enhances the stability of the mature growth hormone receptor. Endocrinology. 2005 Nov;146(11):4755-65.   16081639 
Cowan JW, Wang X, Guan R, He K, Jiang J, Baumann G, Black RA, Wolfe MS, Frank SJ. Growth hormone receptor is a target for presenilin-dependent gamma-secretase cleavage. J Biol Chem. 2005 May 13;280(19):19331-42.
 		 15743767 
Jiang J, Wang X, He K, Li X, Chen C, Sayeski PP, Waters MJ, Frank SJ A conformationally-sensitive growth hormone receptor antibody: impact on GH signaling and GHR proteolysis. Mol. Endocrinol. 2004 Dec;18(12):2981-96.   15345746 
Huang Y, Chang Y, Wang X, Jiang J, Frank SJ. Growth hormone alters epidermal growth factor receptor binding affinity via activation of extracellular signal-regulated kinases in 3T3-F442A cells. Endocrinology. 2004 Jul;145(7):3297-306. 2004
 		 15070853 
Huang Y, Kim SO, Yang N, Jiang J, Frank SJ. Physical and functional interaction of growth hormone and insulin-like growth factor-I signaling elements. Mol Endocrinol. 2004 Jun;18(6):1471-85. 2004  15044591 
Yang N, Huang Y, Jiang J, Frank SJ. Caveolar and lipid raft localization of the growth hormone receptor and its signaling elements: impact on growth hormone signaling. J Biol Chem. 2004 May 14;279(20):20898-905. 2004
 		 15010456 
He K, Wang X, Jiang J, Guan R, Bernstein KE, Sayeski PP, Frank SJ. Janus kinase 2 determinants for growth hormone receptor association, surface assembly, and signaling. Mol Endocrinol. 2003 Nov;17(11):2211-27. 2003
 		 12920237 
Wang X, He K, Gerhart M, Jiang J, Paxton RJ, Menon RK, Black RA, Baumann G, Frank SJ. Reduced proteolysis of rabbit growth hormone (GH) receptor substituted with mouse GH receptor cleavage site. Mol Endocrinol. 2003 Oct;17(10):1931-43. 2003  12829808  
Huang Y, Kim SO, Jiang J, Frank SJ. Growth hormone-induced phosphorylation of epidermal growth factor (EGF) receptor in 3T3-F442A cells. Modulation of EGF-induced trafficking and signaling. J Biol Chem. 2003 May 23;278(21):18902-13, 2003   12642595 
Kim, S.-O., Loesch, K., Wang, X., Jiang, J., Mei, L., Cunnick, J., Wu, J., Frank, S.J. A Role for Grb2-associated binder (Gab)-1 in Growth Hormone Signaling., Endocrinology, 143(12): 4856-4867, 2002.  12446613 
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.  12403792 
Zhang, Y., Guan, R., Jiang, J., Kopchick, J.J., Black, R.A., Baumann, G., Frank, S.J. GH-induced Dimerization Inhibits Phorbol Ester-stimulated GH Receptor Proteolysis., J. Biol. Chem. 276(27):24565-24573, 2001.  11309389 
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.  11181529 
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.  11108241 
Liang, L., Jiang, J., Frank, S.J. Insulin Receptor Substrate-1-Mediated Enhancement of Growth Hormone-Induced MAP Kinase Activation. Endocrinology 141(9): 3328-3336, 2000.  10965905 
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.  10585492 
Zhang, Y., Jiang, J., Kopchick, J.J., Frank, S.J. Disulfide Linkage of Growth Hormone Receptors Reflects GH-induced GHR Dimerization: Association of JAK2 with the GHR is Enhanced by Receptor Dimerization. J. Biol. Chem. 274 (46): 33072-33084, 1999.  10551877 
 

Keywords
growth hormone, signaling, prolactin, IGF-1, growth factors