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Gary D. Hammer, M.D. , Ph.D.
~Mille Schembechler Professor of Adrenal Cancer
~Associate Professor of Internal Medicine and Molecular & IntegrativePhysiology
Ph.D. Tufts University, 1992
5550 MSRB II
(734) 763-3056
ghammer@umich.edu
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Dr. Gary D. Hammer, M.D., Ph.D. is a medical endocrinologist
specializing in the treatment of adrenal diseases. Work in
his laboratory has focused on the mechanisms by which signaling and
transcriptional programs initiate adrenal-specific growth and
differentiation with an emphasis on the dysregulated growth of
adrenocortical stem cells in development and cancer.
Current Research:
Studies in his laboratory are detailed below:
1) Inhibin is an essential component of the
hypothalamic-pituitary-gonadal axis. Produced in granulosa and sertoli
cells, it provides negative feedback to pituitary FSH synthesis and
secretion. In addition, inhibin plays an autocrine/paracrine role in
both the adrenal cortex and gonad. Inhibin null mice develop
spontaneous gonadal tumors and when gonadectomized, adrenocortical
blastomas. We aim to elucidate how stem cells contribute to the
development of the sex-steroid producing adrenocortical and gonadal
neoplasms in inhibin null mice. In addition, our work explored the
autocrine role of inhibin in this process.
2) Wnt ligands are essential stem cell renewal factors. Our
laboratory studies the role of Wnt ligands in adrenocortical stem cell
biology and how dysregulated Wnt signaling through beta-catenin
contributes to adrenocortical carcinoma in mice and human patients.
3) SF-1 is an orphan nuclear receptor that is essential for
adrenocortical and gonadal formation. We aim to understand the
mitogenic signaling mechanisms that initiate the assembly of the orphan
nuclear receptor SF-1 transcription complex using a combination of
biochemical and proteomic technologies such as chromatin
immunoprecipitation assays and tandem affinity purification protocols.
4) We utilize genetic approaches including positional cloning and
candidate gene screening to characterize genes that direct the
adrenogonadal developmental program and contribute to the development of
cancer. We have recently cloned the gene responsible for adrenocortical
dysplasia. Acd is a novel telomere binding protein. We are interested
in the role of telomere maintenance in adrenocortical stem cell renewal
and the development of adrenocortical carcinoma. Detailed phenotypic
analysis reveals that in addition to adrenal dysplasia, the acd mice
present with additional profound urogenital defects restricted to the
kidneys and gonads. Female acd mice exhibit subnormal fertility and
males are completely infertile due to germ cell degeneration in the
testes and an overall decrease in folliculogenesis in the ovary. In
addition, 50% of adult mice develop hydronephrosis due to ureteral
hyperplasia. We are currently exploring the mechanism of action of the
novel gene to elucidate the role of telomere maintenance in urogenital
ridge growth in development and disease.
Representative
Publications:
Keegan, C.E. and Hammer, G.D. Recent Insights into Organogenesis of the Adrenal Cortex. Trends in Endocrinology and Metabolism 13(5): 200-208 (2002).
Beuschlein, F.and Hammer, G.D. Ectopic POMC Syndromes in Endocrine
Manifestations of Systemic Disease. Endocrinology Clinics of North America 31: 1-44 (2002).
Beuschlein, F., Looyenga, B.D., Mutch, C., Bleasdale, S., Bavers, D.L.,
Parlow, A.F., Nilson, J.H. and Hammer, G.D. Activin induces X-zone
apoptosis that inhibits luteinizing hormone-dependent adrenocortical
tumor formation in inhibin deficient mice. Molecular and Cellular
Biology 23(11): 3951-3964 (2003).
Gummow, BM, Winnay, JN and Hammer GD. Convergence of Wnt signaling and SF-1 on transcription of the rat inhibin alpha gene. Journal of
Biological Chemistry 278 (29): 26572-26579 (2003).
Kennell, J.A., E.E. OLeary, B.M. Gummow, Gary D. Hammer, and O.A.
MacDougald. 2003. TCF-4N, a novel isoform of mouse TCF-4, synergizes
with beta-catenin to coactivate C/EBP and SF-1 transcription factors.
Molecular and Cellular Biology 23(15):5366-75 (2003).
Beuschlein, F., Looyenga, B.D., Reincke, M. and Hammer, G.D. Role of
the Inhibin/activin System and Luteinizing Hormone in Adrenocortical
Tumorigenesis. Hormone and Metabolic Research 36: 392-396 (2004).
Hammer, G.D., Tyrrell, J.B., Lamborn, K.R., Applebury, C.B., Elizabeth
T. Hannegan, E.T., Bell, S., Rahl, R., Lu, A. and Wilson, C.B.
Transphenoidal Microsurgery for Cushing's Disease: Initial Outcome and
Long Term Results. Journal of Endocrinology and Metabolism. (12) (2004)
Keegan, C.E., Hutz, J.E., Else, T., Adamska, M., Shah, S.P., Kent,
A.E., Howes, J.M., Beamer, W.G. and Hammer, G.D. Urogenital and caudal dysgenesis in adrenocortical dysplasia (acd) mice is caused by a
splicing mutation in a novel telomeric regulator. Human Molecular
Genetics 14 (1) 2005
Hammer, G.D., Parker, K.L. and Schimmer, B.P. Transcriptional Control of Adrenocortical Development. Endocrinology 146(3): 1018-24 (2005)
Park, S.Y. Raverot, G., Meeks, J.J., Pfaff, L.E., Weiss, J., Hammer, G.D. and Jameson, J.L. Nuclear Receptors Sf1 and Dax1 Function Cooperatively to Mediate Somatic Cell Differentiation During Testis. Development 132(10): 2415-2423 (2005)
Schteingart DE, Doherty GM, Gauger PG, Giordano TJ, Hammer GD, Korobkin M and Worden F. Management of Patients with Adrenal Cancer: Recommendations of an International Consensus Conference. Endocrine-Related Cancer 12(13): 667-80 (2005)
Winnay, JN and Hammer, GD. Characterization of ACTH-dependent signaling pathways regulating cyclic assembly of SF-1-dependent transcriptional complexes. Molecular Endocrinology (In Press, 2005)
Else, T and Hammer GD. Analysis of Adrenal Absence: Agenesis and aplasia. Trends in Endocrinology and Metabolism. (In Press, 2005)
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