Principal Investigator
Edison Biotechnology Institute

Goll Ohio Eminent Scholar & Professor of Molecular Biology

Professor
Department of Biomedical Sciences
College of Osteopathic Medicine

Faculty Affiliate
Molecular and Cellular Biology Program

Education

1972
B.S., Biology
Indiana University of Pennsylvania, Indiana, PA

1975
M.S., Biology-Chemistry
Indiana University of Pennsylvania, Indiana, PA

1980
Ph.D., Virology-Biomedical Sciences
Graduate School of Biomedical Sciences, University of Texas System Cancer Center
M.D. Anderson Hospital and Tumor Institute, Houston, TX

Research associates

Scientific Staff
Darlene Berryman, Assistant Professor
Ryan Clark, Molecular Biology Technician
Elahu Gosney, Molecular Biology Technician
Bruce Kelder, Ph.D., Scientist
Ed List, Post-doctoral Fellow
Shigeru (Nick) Okada, Ph.D., Scientist
Sudha Sankaran, Research Assistant

Graduate Students
Juan Ding

Research interests

My group and I focus on the molecular biology of growth, obesity, insulin resistance, diabetes, and aging. All of our projects use animal models and a proteomics approach to investigate and understand the molecular and cellular events leading to the onset and progression of diseases and the aging process. The goal is to discover biomarkers which can be developed into therapeutics, therapeutic targets, and diagnostics.

An understanding of the molecular basis of growth hormone (GH) action is important, since GH is currently used as a human therapeutic and as a milk production enhancer in animals. The long-term goal of my laboratory is to identify signaling intermediates in GH responsive tissue in vivo.

An approach to this problem has been to generate transgenic mice that express GH or GH antagonists, a new class of human therapeutics discovered in our laboratory. We also use a gene disruption approach. In this case we have "knocked" out the GH receptor gene. The resulting animals are dwarf. Using these models, we evaluate biochemical, endocrine, and physiological properties of these animals and identify signaling intermediates in GH responsive tissue. Also, we use these animals to determine the combined effects of GH and GH antagonists in diabetes-induced end-organ damage. We have recently shown that GH antagonists protect mice from diabetes-induced nephropathy.

Professional activities and memberships

Editorial boards
Journal of Biological Chemistry, June 1995 to 2000
Endocrinology, January 2003 to present
Growth Hormone and IGF Research, January 2003 to present
Molecular Endocrinology, January 2001 to present

Professional organizations
American Association for the Advancement of Science
The American Society for Biochemistry and Molecular Biology
American Society of Microbiology
Endocrinology Society
Growth Hormone and IGF-1 Society
Phi Kappa Phi
Pituitary Society
Sigma Xi

Selected publications

Maamra, M., Kopchick, J.J., Strasburger, C.J. and Ross, R.J.M. Pegvisomant, a growth hormone specific antagonist, undergoes cellular internalization. J. Clinical Endocrinology and Metabolism, 2004, 89(9):4532-4537.

Bartke, A., Peluso, M.R., Moretz, N., Wright, C., Bonkowski, M., Winters, T.A., Shanahan, M.F., Kopchick, J.J., Banz,W.J. Effects of Soy-derived diets on plasma and liver lipids, glucose tolerance, and longevity in normal, long-lived and short-lived mice. Horm. Metab. Res. 2004, 36(8):550-558.

Iida, K., Itoh, E., Kim, D.S., del Rincon, J.P., Coschigano, K.T., Kopchick, J.J. and Thorner, M.O. Muscle mechano growth factor is preferentially induced by growth hormone (GH) and GH deficient lit/lit mice. J. Phys., 2004. 15:560 L Pt 2):341-349.

Nass, R., Liu, J., Hellmann, P., Coschigano, K.T., Gaylinn, B., Berryman, D.E. , Kopchick, J.J., Thorner, M.O. Chronic changes in peripheral growth hormone levels do not affect ghrelin stomach mRNA expression and serum ghrelin levels in three transgenic mouse models. J. Neuroendocrinology, 2004, 16(8):669-675.

Pennisi, P.A., Kopchick, J., Thorgeirsson, S., LeRoith, D. and Yakar, S. Role of growth hormone (GH) in liver regeneration. Endocrinology, 2004, 145(10):4748-4755.

Berryman, D.E., List, E.O., Coschigano, K.T., Behar, K., Kim, Jason, K. and Kopchick, J.J. Comparing adiposity profiles in three mouse models. Growth Hormone & IGF Research, 2004, 14:309-318.

Iida, K., Del Rincon, J.P., Kim, D.S., Itoh, E., Coschigano, K.T., Kopchick, J.J. and Thorner, M.O. Regulation of full-length and truncated growth hormone (GH) receptor by GH in tissues of lit/lit or bovine GH transgenic mice. Am. J. Physiol. Endo. Metab., 2004, 287:E566-E573.

Liu, J.L., Coschigano, K.T., Robertson, K., Lipsett, M., Guo, Y., Kopchick, J.J., Kumar,U., and Liu, Y.L. Disruption of growth hormone receptor gene causes diminished pancreatic islet size and increased insulin sensitivity in mice. Am. J. Physiol. Endo. Metab., 2004, 287:E405-413.

Muller, A.F., Kopchick, J.J., Flyvbjer, A and van der Lely, A.J. Growth Hormone Receptor Antagonists. Clinical Review 166, Clinical Endocrinology & Metabolism, 2004, 89(4):1503.

Mellwain, D.L., Hoke, V.B., Kopchick, J.J., Fuller, C.R. and Lund, P.K. Differential inhibition of postnatal brain, spinal cord and body growth by a growth hormone antagonist. Neuroscience, 2004, 23:5(1):6.

Wang, J., Zhou, J., Cheng, C.M., Kopchick, J.J. and Bondy, C.A. Evidence supporting dual, Igf1-independent and Igf1-dependent, roles for GH in promoting longitudinal bone growth. Journal of Endocrinology, 2004, 180:247-255.

Iida, K., del Rincon, J.P., Kim, D.S., Itoh, E., Nass, R., Coschigano, K.T., Kopchick, J.J. and Thorner, M.O. Tissue-specific regulation of growth hormone (GH) receptor and insulin-like growth factor-I gene expression in the pituitary and liver of GH deficient (lit/lit) mice and ransgenic mice that overexpress bGH or a bGH antagonist. Endocrinology, 2004, 145:1564-1570.

Flint, D.J., Binart, N., Kopchick, J.J. Kelly P. Effects of growth hormone and prolactin on adipose tissue development and function. Pituitary, 2004, 6(2):97-102, review.

Yakar, S., Setser, J., Zhao, H., Stannard, B., Haluzik, M., Glatt, V., Bouxsein, M.L., Kopchick, J.J. and LeRoith, D. Inhibition of growth hormone action improves insulin sensitivity in liver IGF-1-deficient mice. J. Clin. Invest., 2004, 113:96-105.

Wang, J., Zhou, J., Cheng, C. M., Kopchick, J. J., and Bondy, C. A. Evidence supporting dual, IGF-I-independent and IGF-I-dependent, roles for GH in promoting longitudinal bone growth. J Endocrinology, 2004, 180, 247-255.

Kopchick, J.J. Pegvisomant: A new drug entity for acromegaly. MIMS Advances, May 2004.

Keiji, I., del Rincon, J.P., Kim, D.S., Itoh, E., Coschigano, K.T., Kopchick, J.J. and Thorner, M.O. Regulation of full-length and truncated growth hormone (GH) receptor by GH in tissues of lit/lit or bovine GH transgenic mice. Am. Jour. Physiol., Endo. Metab., 2004.

Smid, J.R., Rowland, J.E., Young,W.G., Daley, T.J., Coschigano, K.T., Kopchick, J.J. and Waters, M.J. Mouse cellular cementum is highly dependent on growth hormone status. J. Dent. Res., 2004, 83(1):35-39.

Nass, R., Liu, J., Hellman, P., Coschigano, K.T., Gaylinn, B., Berryman, D.E., Kopchick, J.J. and Thorner, M.O. Chronic changes in peripheral growth hormone levels do not affect ghrelin stomach mRNA expression and serum chrelin levels in three transgenic mouse models. J. of Neuroendocrinology, 2004, 16:669-675.

Young,W.G., Ramirez-Yanez, G.O., Daley, T.J., Smid, J.R., Coschigano, K.T., Kopchick, J.J. and Waters, M.J. Growth hormone and epidermal growth factor in salivary glands of giant and dwarf transgenic mice. J. Histochem. Cytochem, 2004, 52:1191-1197.

Kopchick, J.J. History and future of growth hormone research. Horm. Res. 2003:60 Suppl. 3:103-112, review.

Coschigano, K.T., Holland, A.N., Riders, M.E., List, E.O., Flyvbjerg, A., Kopchick, J.J. Deletion, but not antagonism, of the mouse growth hormone receptor results in severely decreased body weights, insulin and IGF-1 levels and increased lifespan. Endocrinology, 2003, 144(9):3799-3810.

Bernichtein, S., Kayser, C., Dillner, K., Moulin, S., Kopchick, J.J., Martial, J.A., Norstedt, G., Isaksson, O., Kelly, P.A., Goffin, V. Development of pure prolactin receptor antagonists. Journal of Biological Chemistry, 2003, 278:38:35988-35999.

Kopchick, J.J. Discovery and mechanism of action of pegvisomant. Society of the European Journal of Endocrinology, 2003, 148:Suppl 2:S21-S.

Parsons, S.A., Banks, G.B., Rowland, J.A., Coschigano, K.T., Kopchick, J.J., Waters, M.J. and Noakes, P.G. Genetic disruption of the growth hormone receptor does not influence motoneuron survival in the developing mouse. Int. J. Devl. Biol., 2003. 47:41-49.

Bartke, A., Chandrashekar, V., Dominici, F., turyn, D., Kinney, B., Steger, R., Kopchick, J.J. Insulin-like growth factor 1 (IGF-1) and aging: controversies and new insights. Biogerontology, 2003, 4(1):1-8.

Li, Y., Knapp, J.R., and Kopchick, J.J. Enlargement of interscapular brown adipose tissue in growth hormone antagonist transgenic and in growth hormone receptor gene-disrupted dwarf mice. Society for Experimental Biology and Medicine, 2003, 207-215.

Bartke, A., Kopchick, J.J., Dominici, F., Turyn, D. IGF-1 and insulin signaling in the control of longevity. Book: Endocrine Aspects of Successful Aging: Genes, Hormones and Lifestyles, 2003, 19-33.

Li, Y., Knapp, J.R. and Kopchick, J.J. Enlargement of interscapular brown adipose tissue in growth hormone antagonist transgenic and in growth hormone receptor gene-disrupted dwarf mice. Exp. Biol. Med. (Maywood) 2003, 228, 207-215.

Higashimori, T., Kim, H.J., Coschigano, K.T., Park, S.Y., Choi, H., Kopchick, J.J., Shulman, G.I., and Kim, J.K. Transgenic mice overexpressing growth hormone are insulin resistant due to decreased insulin-stimulated glucose uptake in skeletal muscle and adipose tissue. Paper presented at American Diabetes Association 63 rd Scientific Sessions (New Orleans, LA). 2003.

Kohn, D.T. and Kopchick, J.J. Growth hormone receptor antagonists. Minerva Endocrinologica, 2002, 27:4:287-298.

Kelly, P.A., Bachelot,A., Kedzia, C., Hennighausen, L., Ormandy, C.J., Kopchick, J.J., Binart, N. The role of prolactin and growth hormone in mammary gland development. Molecular & Cellular Endocrinology, 2002, 197:1-2, 127-131.

Miller, R.A., Chang, Y., Galecki, A.T., Al-Regaiey, K., Kopchick, J.J. and Bartke, A. Gene expression patterns in calorically restricted mice: partial overlap with long-lived mutant mice. Molecular Endocrinology, 2002, 16(11):2657-2666.

Hauck, S.J., Aaron, J.M, Wright, C., Kopchick, J.J. and Bartke, A. Antioxidant Enzymes, free-radical damage, and response to paraquat in liver and kidney of long-living growth hormone receptor/binding protein gene-disrupted mice. Hormone and Metabolic Research, 2002, 34:481-486.

Kopchick, J.J., Parkinson, C., Stevens, E.C. and Trainer, P.J. Growth hormone receptor antagonists: discovery, development, and use in patients with acromegaly. Endocrine Reviews, 2002, 23:5:623-646.

Leonard, A.E., Kelder, B., Bobik, E.G., Chuang, L.T., Lewis, C.J., Kopchick, J.J., Mukerji, P. and Huang, Y.S. Identification and expression of mammalian long-chain PUFA elongation enzymes. Lipids, 2002, 37(8):733-740.

Zaczek, D., Hammond, J., Suen, L.,Wandji, S., Service, D., Bartke, A., Chandrashekar, V., Coschigano, K. and Kopchick, J.J. Impact of growth hormone resistance on female reproductive function: New insights from growth hormone receptor knockout mice. Biology of Reproduction, 2002, 67:1115-1124.

Bachelot, A., Monget, P., Imbert-Bollore, P., Coschigano, K., Kopchick, J.J., Kelly, P.A. and Binart, N. Growth hormone is required for ovarian follicular growth. Endocrinology, 2002, 143, 4104-4112.

Keene, D.E., Suescun, M.O., Bostwick, M.G., Chandrashekar, V., Bartke, A. and Kopchick, J. Puberty is delayed in male growth hormone receptor gene disrupted mice. Journal of Andrology, 2002, 23:661-668.

Kopchick, J.J., List, E.O., Kohn, D.T., Keidan, G.M.O., Qiu, L. and Okada, S. Perspective: Proteomics – See "Spots" Run. Endocrinology, 2002, 143(6):1990-1004.

Kopchick, J.J. In vitro mutagenesis of the Growth Hormone Gene. GH and Growth Factors, Current Medical Literature, 2002, 17:27-32.

Bachelot, A., Monget, P., Imbert-Bollore, P., Coschigano, Kopchick, J.J., Kelly, P.A. and Binart, N. Growth hormone is required forovarian follicular growth. Endocrinology, 2002, 13:4104-4112.

Chandrashekar, V., Bartke, A., Awoniyi, C.A., Tsai-Morris, C.H., Dufau, M.L., Russell, L.D. and Kopchick, J.J. Testicular Endocrine Function in GH Receptor Gene Disrupted Mice. Endocrinology, 142(8):3443-3450, 2001.

Okada, S. and Kopchick, J.J. Biological effects of growth hormone and its antagonist. Trends in Molecular Medicine, 7:3:126-132, 2001.

Li, Yunsheng, Kelder, Bruce, and Kopchick, J.J., Identification, Isolation, and Cloning of Growth Hormone (GH)-Induced Interscapular Brown Adipose Complementary Deoxyribonucleic Acid from GH Antagonist Mice. Endocrinology, 142:2937-2945, 2001.

Bellush, L.L., Doublier, S., Holland, A.N., Striker, L.J., Striker, G.E. and Kopchick, J.J. Protection against diabetes-induced nephropathy in growth hormone receptor/binding protein gene-disrupted mice. Endocrinology, 141:1:163-168, 2000.

Coschigano, K.T., Clemmons, D., Bellush, L.L. and Kopchick, J.J. Assessment of Growth Parameters and Life Span of GHR/BP Gene-Disrupted Mice. Endocrinology, 141:2608-2613, 2000.

Chen, N., Chen,W., Striker, L., Striker, G.E. and Kopchick, J.J. Coexpression of a bovine growth hormone (GH) and a human GH antagonist gene in transgenic mice. Endocrinology,138:2:851-854, 1997.

Kopchick, J.J. and Woodley, F.W. Regulation of Growth Hormone Gene Expression, in Advances in Molecular and Cellular Endocrinology, Chapter 3, 1:51-82, 1997.

Chen, N., Chen, W. and Kopchick, J.J. Liver and kidney growth hormone (GH) receptors are differently regulated in diabetic GH and GH antagonist transgenic mice. Endocrinology, 138:5:1988-1994, 1997.

Yang, C.W., Striker, G.E., Chen,W.Y., Kopchick, J.J. and Striker, L.J. Differential expression of glomerular extracellular matrixand growth factor mRNA in rapid and slowly progressive glomerulosclerosis: studies in mice transgenic for native or mutated growth hormone. Laboratory Investigation, 76:4:467-476, 1997.

Smith, L.E.H., Kopchick, J.J., Chen,W., Knapp, J., Kinose, F., Daley, D., Foley, E., Smith, R.G., and Schaeffer, J.M. Essential Role of Growth Hormone in Ischemia-Induced Retinal Neovascularization. Science, 276:1706-1709, 1997.

Hansen, J.A., Hansen, L.H.,Wang, X., Kopchick, J.J., Gouilleux, F., Groner, B., Nielsen, J.H., Perregaard, A.M., Galsgaard, E.D. and Billestrup, N. The role of growth hormone receptor tyrosine phosphorylation in Stat5 activation. Journal of Molecular Endocrinology, 18: 213-221, 1997.

Thurmond, J. M., Hards, R. G., Seipelt, C. T., Leonard, A. E.,Hansson, L., Stromqvist, M., Systrom, M., Enquist, K., Xu, B. C., Kopchick, J. J. and Mukerji, P. Phosphorylation of a recombinant human protein in Escherichia coli. Protein Expression and Purification, 10:202-208, 1997.

Zhou, Y., He, L., Baumann, G. and Kopchick, J.J. Deletion of the mouse growth hormone binding protein (mGHBP) mRNA polyadenylation and splicing sites does not abolish production of mGHBP. Journal of Molecular Endocrinology, 19:1-13, 1997.

Kopchick, J.J. and Chen,W. Structure/function relationships of GH and other members of the GH family. Handbook of Physiology, Hormone Control of Growth 137:145-162, 1998.

Zhou, Y., Xu, B.C., Maheshwari, H.G., He, L., Reed, M., Lozykowski, M., Cataldo, L.A., Chen, N., Okada, S., Knapp, J.R.,Wagner, T.E., Baumann, G. and Kopchick, J.J.: A Mammalian model for Laron syndrome produced by targeted disruption of the growth hormone receptor/binding protein gene (the Laron mouse). Proc. Nat. Acad. Sci., USA, 94:24, 13215-13220, 1997.

Chen, W.Y., Wight, D.C., Mehta, B.V.,Wagner, T.E. and Kopchick, J.J. Glycine 119 of bovine growth hormone is critical for growth promoting activity. Molecular Endocrinology, 5:12, 1845-1852, 1991.

Chen, W.Y., Wight, D.C., Wagner, T.E., and Kopchick, J.J. Expression of a mutated bovine growth hormone gene suppresses growth of transgenic mice. Proc. Natl. Acad. Sci., USA, 87:13, 5061-5065, 1990.