Professor of Internal Medicine,
Professor of Molecular and Integrative Physiology,
Professor of Cell and Developmental Biology
Gary D. Hammer, M.D., Ph.D. serves as the Director of the Endocrine Oncology Program in the Comprehensive Cancer Center at UM where he holds the Millie Schembechler Professorship in Adrenal Cancer. Under his leadership, the Program was selected as one of five inaugural Destination Programs singled out for research and clinical excellence at UMHS. The Program is uniquely recognized as an international center of excellence for the treatment of adrenal cancer.
He is also tthe Director of the University’s Center for Organogenesis that brings together groups and faculty – basic scientists and clinicians – focused on organ-specific problems spanning developmental disorders to cancer. Strong relationships with the stem cell community, tissue and biomedical engineering and clinical programs provide unparalleled opportunity for translational partnerships.
Research projects in his own laboratory are aimed at elucidating the mechanisms by which growth factor signaling and transcriptional programs initiate adrenal-specific growth and differentiation with an emphasis on dysregulated growth of adrenocortical stem/progenitor cells in development and cancer. This work has led to the development of new national and international therapeutic trials with biological-based therapies for adrenal cancer that target the molecular defects in cancer stem cells while sparing normal tissue.
In only 11 years, Gary Hammer has become the world leader in adrenal development and adrenal cancer. His work is transformational. His research on SF1 activation by signaling pathways changed the paradigm of orphan nuclear receptor action. Subsequent studies on sumoylation and CDK7-mediated phosphorylation set the stage for how dynamic signaling controls the homeostasis of adrenal development (proliferating versus differentiating cells). Hammer single-handedly defined adrenal stem and progenitor cells and the critical signaling/transcriptional programs that dictate cell fate, self-renewal and multipotency in health and disease. Lastly, he has eloquently translated these discoveries into the first targeted therapies for adrenal cancer.
- Hammer GD and Kapp BS. The effects of naloxone administered into the periaqueductal gray on the shock-elicited freezing behavior in the rat. Behavioral and Neural Biology 46: 189-195 (1986).
- Hammer GD, Fairchild-Huntress V and Low MJ. Pituitary-specific and hormonally regulated gene expression directed by the rat proopiomelanocortin promoter in transgenic mice. Molecular Endocrinology 4 (11): 1689-1697 (1990).
- Hammer GD, Muller G, Liu B, Petrides JS, Roos BA and Low MJ. Ectopic corticotropin-releasing hormone produced by a transfected cell line chronically activates the pituitary-adrenal axis in trankaryotic rats. Endocrinology 130 (4): 1975-1985 (1992).
- Liu B, Hammer GD, Rubinstein M, Mortrud M and Low MJ. Identification of DNA elements cooperatively activating proopiomelanocortin gene expression in the pituitary gland of transgenic mice. Molecular and Cellular Biology. 12 (9): 3978-3900 (1992).
- Asa SL, Kovacs K, Hammer GD, Liu B, Roos BA and Low MJ. Pituitary corticotroph hyperplasia in rats implanted with a medullary thyroid carcinoma cell line transfected with a corticotropin-releasing hormone cDNA expression vector. Endocrinology 131 (2): 715-720 (1992).
- Low MJ, Liu B, Hammer GD, Rubinstein M and Allen RG. Posttranslational processing of proopiomelanocortin (POMC) in mouse pituitary melanotroph tumors induced by a POMC-simian virus 40 large T antigen transgene. Journal of Biological Chemistry 268 (33): 24967-24975 (1993).
- Nachtigal MW, Horokawa Y, Enyeart Van Houten DL, Flanagan JN, Hammer GD and Ingraham HA. Wilms’ Tumor 1 and Dax-1 modulate the orphan nuclear receptor SF-1 in sex-specific gene expression. Cell 93 (3): 445-454 (1998).
- Hammer GD, Kylova I, Zhang Y, Darimont BD, Simpson K, Weigel NL and Ingraham HA. Phosphorylation of the nuclear receptor SF-1 modulates cofactor recruitment: Integration of hormone signaling in reproduction and stress. Molecular Cell 3 (4): 521-526 (1999).
- Hammer GD and Ingraham HA. Steroidogenic Factor 1: Its role in endocrine organ development and differentiation. (invited, peer-reviewed) Frontiers in Neuroendocrinology 20: 199-223 (1999).
- Babu PS, Bavers DL, Beuschlein F, Shah S, Jeffs B, Jameson JL and Hammer GD. Interaction between Dax-1 and SF-1 in vivo: Increased adrenal responsiveness to ACTH in the Absence of Dax-1. Endocrinology 143 (2): 665-673 (2002).
- Beuschlein F, Mutch C, Bavers DL, Ulrich-Lai Y, Engeland WC, Keegan C and Hammer GD. Steroidogenic Factor-1 is essential for compensatory adrenal growth following unilateral adrenalectomy. Endocrinology 143 (8): 3122-35 (2002).
- Keegan CE and Hammer GD. Recent Insights into Organogenesis of the Adrenal Cortex. (invited, peer-reviewed) Trends in Endocrinology and Metabolism 13 (5): 200-208 (2002).
- Beuschlein F and Hammer GD. Ectopic POMC Syndromes in Endocrine Manifestations of Systemic Disease. (invited, peer-reviewed) Endocrinology Clinics of North America 31: 1-44 (2002).
- Beuschlein F, Looyenga BD, Mutch C, Bleasdale S, Bavers DL, Parlow AF, Nilson JH and Hammer GD. 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 JA, OLeary EE, Gummow BM, Hammer GD and MacDougald OA. 2003. TCF-4N, a novel isoform of mouse TCF-4, synergizes with b-catenin to coactivate C/EBPa and SF-1 transcription factors. Molecular and Cellular Biology 23 (15): 5366-75 (2003).
- Beuschlein F, Looyenga BD, Reincke M and Hammer GD. Role of the Inhibin/activin System and Luteinizing Hormone in Adrenocortical Tumorigenesis. (invited, peer-reviewed) Hormone and Metabolic Research 36: 392-396 (2004).
- Hammer GD, Tyrrell JB, Lamborn KR, Applebury CB, Hannegan ET, Bell S, Rahl R., Lu A and Wilson CB. Transphenoidal Microsurgery for Cushing's Disease: Initial Outcome and Long Term Results. Journal of Clinical Endocrinology and Metabolism 89 (12): 6348-6357 (2004).
- Keegan CE, Hutz JE, Else T, Adamska M, Sah SP, Kent AE, Howes J, Beamer WG and Hammer GD. 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): 113-123 (2005).
- Hammer GD, Parker KL and Schimmer BP. Transcriptional Control of Adrenocortical Development. (invited, peer-reviewed) Endocrinology 146 (3): 1018-24 (2005).
- Park SY, Raverot G, Meeks JJ, Pfaff LE, Weiss J, Hammer GD and Jameson JL. 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 (3): 667-680 (2005).
- Else T and Hammer GD. Genetic analysis of adrenal absence: agenesis and aplasia. Trends in Endocrinology and Metabolism 16 (10): 458-468 (2005).
- Winnay JN, Xu Z, O'Malley BW and Hammer GD. SRC‑1‑deficient Mice Exhibit Altered Hypothalamic‑Pituitary‑Adrenal Axis Function. Endocrinology. 147 (3): 1322-32 (2006).
- Winnay JN and Hammer GD. ACTH-mediated signaling cascades coordinate a cyclic pattern of SF-1-dependent transcriptional activation. Mol Endocrinol. 20 (1): 147-166 (2006).
- Hutz JE, Krause AS, Achermannm J, Vilain E, Tauber M, Lecointre C, McCabe ERB, Hammer GD and Keegan CE. IMAGe association and congenital adrenal hypoplasia: No disease-causing mutations found in the ACD gene. Molecular Genetics and Metabolism 88 (1): 66-70 (2006).
- Martin M and Hammer GD. Pheochromocytoma: Risk Groups, Diagnosis and Management in Primary Care. Hospital Physician 42 (2): 17-24 (2006).
- Beuschlein F, Slawik M, Shapiro I, Hartmann M, Wudy S, Hammer GD and Reincke M. Gonadectomy in mice of the inbred strain CE/J induces proliferation of subcapsular adrenal cells expressing gonadal marker genes. Journal of Endocrinology 190 (1): 47-57 (2006).
- Looyenga BD and Hammer GD. Origin and Identity of Adrenocortical Tumors in Inhibin Knockout Mice: Implications for Cellular Plasticity in the Adrenal Cortex. Molecular Endocrinology 20 (11): 2848-63 (2006)
- Gummow BM, Scheys JO, Cancelli VR and Hammer GD. Reciprocal Regulation of a GR-SF-1 Transcription Complex on the Dax-1 Promoter by Glucocorticoids and ACTH in the Adrenal Cortex. Molecular Endocrinology 20 (11): 2711-23 (2006)
- Lichtenauer U, Duchniewicz M, Kolanczyk M, Höflich A, Hahner S, Else T, Bicknell AB, Tomasz Zemojtel T, Stallings NR, Hammer GD, Scheele J and Beuschlein F. Pbx-1 and SF-1 synergistically affect adrenocortical growth and steroidogenesis. Endocrinology 148 (2): 693-704 (2007).
- Kim A and Hammer GD. Functional Characterization of Undifferentiated Adrenocortical Cells with Stem/Progenitor Cell Properties: Review of Literature and Recent Advances. (invited, peer-reviewed) Molecular and Cellular Endocrinology 265-266: 10-16 (2007).
- Keegan CE, Hutz JE, Krause AS, Koehler K, Metherell LA, Boikos S, Stergiopoulos S, Clark AJ, Stratakis CA, Huebner A, and Hammer GD. Novel polymorphisms and lack of mutations in the ACD gene in patients with ACTH resistance syndromes. Clinical Endocrinology; 67(2): 168-174 (2007).
- Hockemeyer D, Else T, Daniels J-P., Palm W, Ye JZ-S., deLange T, and Hammer GD. Cooperative telomere protection provides evidence for correspondence of POT1/TPP1 to ciliate TEBPα/β. Nature Structural and Molecular Biology 14(8): 754-61 (2007)
- Looyenga BD and Hammer GD. Genetic Removal of Smad3 from Inhibin-null Mice Attenuates Tumor Progression by Uncoupling Extracellular Mitogenic Signals from the Cell Cycle Machinery. Molecular Endocrinology 21: 2440-2457 (2007).
- Else T, Theisen BK, Hutz JE, Keegan CE, Hammer GD and Ferguson DO. Tpp1/Acd maintains genomic stability through a complex role in telomere protection. Chromosome Research 15(8): 1001-13 (2007)
- Barlaskar FM and Hammer GD. The molecular genetics of adrenocortical carcinoma. Rev Endocr Metab Disord 8(4): 343-8 (2007) (invited, peer-reviewed)
- Else T, Giordano TJ, Hammer GD. Evaluation of telomere length maintenance mechanisms in adrenocortical carcinoma. J Clin Endocrinol Metab. Apr;93(4):1442-9 (2008)
- Rui X, Tsao J, Scheys JO, Hammer GD, Schimmer BP. Contributions of Sp1 and Steroidogenic Factor 1 to Adcy4 Expression in Y1 Mouse Adrenal Cells. Endocrinology 149(7) 3668-78. (2008)
- Kim AC, Reuter AL Zubair M, Serecky K, Else T, Bingham NC, Lavery GG, Parker KL and Hammer GD. Targeted Disruption of b-catenin in Sf-1-expressing Cells Impairs Development and Maintenance of the Adrenal Cortex. Development 135 (15): 2593-602 (2008)
- White ML, Cho KJ, Gauger PG, Doherty GM, Hammer GD, Miller BS. The Role of Radiologic Studies in the Evaluation and Management of Primary Hyperaldosteronism. Surgery 2008 Surgery. 144(6):926-33 (2008)
- Giordano TJ, Kuick R, Else T, Gauger PG, Vinco M, Bauersfeld J, Sanders D, Thomas DG, Doherty G and Hammer GD. Molecular Classification and Prognostication of Adrenocortical Tumors by Transcriptome Profiling. Clinical Cancer Research. 15(2): 668-76 (2009)
- Barlaskar FM, Spalding AC, Heaton JH, Davis MA, Ben-Josef E, and Hammer GD. The Type 1 Insulin-like Growth Factor Receptor as a Novel Therapeutic Target in Adrenocortical Carcinomas. JCEM. 94(1): 204-12 (2009)
- Yang W-H, Heaton JH, Brevig H, Mukherjee S, Iñiguez-Lluhí JA. and Hammer GD. Sumoylation inhibits SF-1 activity by reducing CDK7 mediated Ser 203 phosphorylation MCB. 29(3): 613-25 (2009)
- Xu B, Yang W-H, Gerin I, Hu C-D, Hammer GD and Koenig RJ. DAX-1 and Steroid Receptor RNA Activator (SRA) Function as Transcriptional Coactivators for Steroidogenic Factor-1 in Steroidogenesis. Molecular and Cellular Biology 29(7):1719-34 (2009)
- Kim AC, Barlaskar FM, Heaton JH, Else T, Kelly VR, Krill KT, Scheys JO, Simon DP, Trovato A, Yang W-H, and Hammer GD. In Search of Adrenocortical Stem and Progenitor Cells. (invited, peer-reviewed) Endocrine Reviews 30 (3): 241-263 (2009)
- Else T, Kim AC, Trovoto A, Ferguson DO, Lucas PC and Hammer GD. Genetic p53 deficiency partially rescues adrencortial dysplasia (acd) phenotype at the expense of increased tumorigenicity. Cancer Cell 15(6): 465-476 (2009)
- Strosberg JR, Hammer GD and Doherty GM. Management of Adrenocortical Carcinoma. (invited, peer-reviewed) Journal of the National Comprehensive Cancer Network 7(7):752-9 (2009)
- Haluska P, Worden F, Olmos D, Yinv D, Schteingart D, Batzel GN, Paccagnella ML, de Bono JS, Richardson RL, Gualberto AG and Hammer GD. Safety, tolerability, and pharmacokinetics of the anti-IGF-1R monoclonal antibody CP-751,871 in patients with refractory adrenocortical carcinoma. Cancer Chemotherapy and Pharmacology 65(4):765-73 (2010)
- Looyenga BD, Wiaters E, Vale WW and Hammer GD. Inhibin-A Antagonizes TGFβ2 Signaling by Downregulating Cell Surface Expression of the TGFβ Co-receptor Betaglycan. Molecular Endocrinology 24(3): 608-620 (2010).
- Watson RL, Spalding AC, Zielske SP, Morgan A, Kim M, Bommer GT, Eldar-Finkelman H, Giordano T, Fearon ER, Hammer GD Lawrence TS and Ben-Josef E. GSK3b and b-catenin Modulate Radiation Cytotoxicity in Pancreatic Cancer. Neoplasia 12(5): 357-365 (2010).
- Garcia-Perez JL, Morell M, Scheys JO, Kulpa DA, Morell S, Carter CC, Hammer GD, Collins KL, O’Shea KS, Menendez P and Moran JV. Efficient and reversible epigenetic silencing of LINE-1 retrotransposition events in embryonic carcinoma cells. Nature 466(7307):769-73 (2010)
- Miller BS, Ammori JB, Gauger PG, Broome JT, Hammer GD, Doherty GM. Laparoscopic resection is inappropriate in patients with known or suspected adrenocortical carcinoma. World J Surg. 34(6):1380-5 (2010)
- Miller BS, Gauger PG, Hammer GD, Giordano TJ and Doherty GM. Ann Arbor Proposal for modification of the ENSAT staging system for adrenocortical carcinoma using tumor grade, Langebeck's Archives of Surgery 395(7): 955-961 (2010)
- Sabolch A, Feng M, Griffith K, Hammer, G, Doherty G, and Ben-Josef E. Adjuvant and Definitive Radiotherapy for Adrenocortical Carcinoma. Int. J. Radiation Oncology Biol. Phys. 80(5):1477-84 (2011)
- Kelly VR, Xu B, Koenig RJ and Hammer GD. Dax1 upregulates OCT4 expression in mouse embryonic stem cells via LRH-1 and SRA. Molecular Endocrinology 24 (12): 2281-2291 (2010)
- Kelly VR and Hammer GD. LRH and Nanog regulate Dax1 transcription in mouse embryonic stem cells. Molecular and Cellular Endocrinology 332(1-2):116-24 (2011)
- Wood MA and Hammer GD. Adrenocortical Stem and Progenitor Cells: Unifying Model of Two Proposed Origins. Molecular and Cellular Endocrinology. 336(1-2):206-12 (2011)
- Dobrosotskaya IY, Hammer GD, Schteingart DE, Maturen KE, and Worden FP. Mebendazole Monotherapy Provides Long-Term Disease Control in Metastatic Adrenocortical Carcinoma. Endocrine Practice March 31:1-13 (2011)
- Scheys JOA, Heaton JH and Hammer GD. Evidence of adrenal failure in aging Dax1-deficient mice. Endocrinology Sep;152(9):3430-9 (2011)
- Nasonkin OI, Ward RD Bavers DL, Beuschlein F, Mortensen AH, Keegan CE, Hammer GD and Camper SA. Prop1 Deficient Dwarf Mice Maintain ACTH Production and Stress Response. PLOS 6(12) 2011
- Simon DP and Hammer GD. Adrenocortical Stem and Progenitor Cells—Implications for Adrenocortical Carcinoma. Molecular and Cellular Endocrinology (Accepted) 2011
- Simon DP, Giordano TJ and Hammer GD. Upregulated JAG1 Enhances Cell Proliferation in Adrenocortical Carcinoma. Clinical Cancer Research (Accepted) 2012 (highlighted on cover)
- Barbra S. Miller, Kathleen M. Ignatoski, Stephanie Daignault, Ceit Lindland, Megan Doherty, Paul G. Gauger, Gary D. Hammer, Stewart C. Wang, Gerard M. Doherty and The University of Michigan Analytical Morphomics Group. Worsening Central Sarcopenia and Increasing Intra-Abdominal Fat Correlate with Decreased Survival in Patients with Adrenocortical Carcinoma. World Journal of Surgery. 2012, DOI: 10.1007/s00268-012-1581-5
- Barbra S. Miller, Paul G. Gauger, Gary D. Hammer and Gerard M. Doherty. Resection of adrenocortical carcinoma is less complete and local recurrence occurs sooner and more often after laparoscopic adrenalectomy than after open adrenalectomy. Surgery (Accepted) 2012
- Heaton JH, Wood MA, Kim AC, Lima LO, Barlaskar FM, Almeida MQ, Fragoso MCBV, Kuick R, Lerario AM, Simon DP, Soares IC, Starnes E, Thomas DG, Latronico AC, Giordano TJ, Hammer GD. Progression to Adrenocortical Tumorigenesis in Mice and Humans through Insulin-like Growth Factor 2 and -catenin. American Journal of Pathology (Accepted) 2012