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 Principal Investigator/Program Director (Last, first, middle):

BIOGRAPHICAL SKETCH

Provide the following information for the Senior/key personnel and other significant contributors.
Follow this format for each person. DO NOT EXCEED FOUR PAGES.

NAME POSITION TITLE

Gary D. Hammer Millie Schembechler Professor of Adrenal Cancer;
Professor of Int Medicine, Mol & Integrative
eRA COMMONS USER NAME (credential, e.g., agency login) Physiology and Cell & Developmental Biology

ghammer

EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, include postdoctoral training and

residency training if applicable.)

INSTITUTION AND LOCATION DEGREE MM/YY FIELD OF STUDY
(if applicable)

University of Vermont B.A. 1985 Psychology

Tufts University School of Medicine M.D. 1992 Medicine

Tufts University School of Grad. Biomed. Sci Ph.D. 1992 Neuroscience

A. Personal Statement
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 the 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 diseases.

B. Positions and Honors

Positions and Employment

1992-1994 Internal Medicine Resident, University of California-San Francisco

1994-1997 Endocrinology and Metabolism Fellow, University of California-San Francisco

1996-1999 Assistant Research Physiologist, University of California-San Francisco

1999-2005 Assistant Professor, Departments of Medicine and Physiology, University of Michigan

2005-2011 Associate Professor, Departments of Medicine and Physiology, University of Michigan

2005-present Millie Schembechler Professor of Adrenal Cancer, University of Michigan

2011-present Professor, Depts of Int Med; Mol & Integrative Phys; Cell & Dev Bio, University of Michigan

Other Experience and Professional Memberships

2000-2003 Minorities Affairs Committee, The Endocrine Society

2000-2008 Student Affairs Committee, The Endocrine Society (Chair 2003-2008)

2002 NIH NIDDK ZDK1 GRB-B (M2): Study Section RFA DK01-026

2002-2009 Editorial Board, Molecular Endocrinology (Inaugural Reviewer of the Year Awardee: 2005)

2007-2010 Annual Meeting Steering Committee, The Endocrine Society

2009 Annual Meeting Trainee Day (Basic Science Chair)

2009-2010 Publication Committee, The Endocrine Society

2010-2013 Council, The Endocrine Society

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 Principal Investigator/Program Director (Last, first, middle):

Honors Outstanding Contribution to Research Award, University of Vermont
1984 Elected Membership, Sigma Xi
1985 Elected Membership, Phi Beta Kappa
1985 Outstanding Senior, Department of Psychology, University of Vermont
1985 Kidder Medal for Outstanding Senior, University of Vermont
1985 Wasson Award for Outstanding Scholar-Athlete, University of Vermont
1985 Earl P Charlton Research Competition, Second Prize, Tufts University School of Medicine
1990 Outstanding Achievement in Neuroscience Award, Tufts University School of Medicine
1992 Merck Senior Fellow Award, Endocrine Society
1999 Gordon Research Conference in Hormone Action Research Award
1999 Outstanding Reviewer Award; Molecular Endocrinology
2005 Jerome Conn Award for Outstanding Research, Department of Medicine, Univ of Michigan
2005 Millie Schembechler Professor of Adrenal Cancer, Univ of Michigan
2005 American Society of Clinical Investigation, inductee
2008 American Association of Physicians, inductee
2012

C. Selected Peer-reviewed Publications (Selected from 66 peer-reviewed publications)

1. 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 (2003). Molecular Cellular Biology 23 (11): 3951-3964. PMID: PMC155220
2. 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 (2005). Human Molecular Genetics 14 (1): 113-123. PMID: 15537664
3. Winnay JN and Hammer GD. ACTH-mediated signaling cascades coordinate a cyclic pattern of SF-1-
dependent transcriptional activation (2006). Molecular Endocrinology 20 (1): 147-166. PMID: 16109736
4. Looyenga BD and Hammer GD. Origin and Identity of Adrenocortical Tumors in Inhibin Knockout Mice:
Implications for Cellular Plasticity in the Adrenal Cortex (2006). Molecular Endocrinology 20 (11): 2848-63.
PMID: 16873442
5. 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 (2006).
Molecular Endocrinology 20 (11): 2711-23. PMID: 16857744
6. 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 (2007). Nature
Structural and Molecular Biology 14(8): 754-61. PMID: 17632522
7. 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 (2007). Molecular
Endocrinology 21: 2440-2457. PMID: 17652186
8. Kim AC, Reuter AL Zubair M, Serecky K, Else T, Bingham NC, Lavery GG, Parker KL and Hammer
GD. Targeted Disruption of -catenin in Sf-1-expressing Cells Impairs Development and Maintenance of the
Adrenal Cortex (2008). Development 135 (15): 2593-602. PMID: 18599507
9. 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 (2009).
Molecular and Cellular Biology 29(7):1719-34. PMCID: 2655620
10. 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 (2009). (invited, peer-
reviewed) Endocrine Reviews 30 (3): 241-263. PMCID: 2726842
11. Else T, Kim AC, Trovoto A, Ferguson DO, Lucas PC and Hammer GD. Genetic p53 deficiency partially
rescues adrenocortical dysplasia (acd) phenotype at the expense of increased tumorigenicity (2009). Cancer
Cell 15(6): 465-476. PMCID: 2703790

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 Principal Investigator/Program Director (Last, first, middle):

12. 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 (2009). Molecular and Cellular Biology
29(3):613-25. PMCID: 630698
13. Kelly VR, Xu B, Koenig RJ and Hammer GD. Dax1 upregulates OCT4 expression in mouse embryonic
stem cells via LRH-1 and SRA (2010). Molecular Endocrinology 24 (12): 2281-2291. PMCID: 2999479
14. Looyenga BD, Waters E, Vale WW and Hammer GD. Inhibin-A Antagonizes TGFβ2 Signaling by
Downregulating Cell Surface Expression of the TGFβ Co-receptor Betaglycan (2010). Molecular Endocrinology
24(3): 608-620. PMCID: 2840806
15. 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 b-catenin (2012).
American Journal of Pathology - In Press: AJP #12-0079

D. Research Support

Ongoing Research Support

R01-DK-062027-09 Hammer (PI) 02/01/09 - 01/31/13

NIH (PI)

Mechanisms of Adrenal Differentiation

Our strategy for this proposal is to focus on the role of SF1 and the SF1 target gene Dax1 in the regulation of

adrenocortical growth maintenance. Based on our preliminary data, we hypothesize that unique transcriptional

programs in subcapsular undifferentiated progenitor cells serve to maintain the functional capacity of the

adrenal cortex. Our specific aims are directed towards a systematic characterization of novel functions of SF1

critical to this process. We propose to determine the origin of SF1 positive subcapsular cells, define the role of

Dax1 in the self-renewal and multipotent properties of these cells in vivo and determine mechanisms by which

SF1 is activated to initiate a unique proliferation-associated transcriptional profile in this population.

R01CA CA134606-03 Hammer (PI) 12/01/09 – 11/30/14

NIH (PI)

Wnt-responsive adrenocortical cells in organ maintenance and cancer
The major goal of this project is to focus on the mechanism and consequences of Wnt-mediated activation of
gene expression in adrenal cancer as it fits in with the objective of understanding the cellular and molecular
mechanisms by which signaling pathways and downstream transcription factors coordinate the specification
of adrenocortical cells within the adrenal gland in health and disease.

Role: PI

288 DP Incent to Collaborate Hammer (PI) 6/01/11 – 05/31/14

University of Michigan (MICHR UL1RR024986) (PI)

Telemedicine in mitotane management for ACC

The major goal of this project is to conduct the clinic trial titled: A randomized comparative trial of an

automated interactive voice response (IVR) system to monitor time to therapeutic serum mitotane levels, dose

adjustment, and symptom management for patients with adrenocortical carcinoma.

Role: PI

OSI-906-301 Hammer (PI) 5/3/10 – 7/31/12

OSI Pharmaceuticals

Phase 3 Study of OSI-906 in Patients with Locally Advanced or Metastatic Adrenocortical Carcinoma

The major goal of this project is to conduct a randomized, double-blind, placebo-controlled trial to test the

efficacy of the IGF1R antagonist OSI-906 in adrenocortical carcinoma.

Role: PI

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 Principal Investigator/Program Director (Last, first, middle):

C107-415 Schteingart (PI) 09/23/09 – 09/23/12

Corcept Therapeutics

Corlux extension study    

The major goal of this project is to conduct an open label extension study of the efficacy and safety of
mifepristone in the treatment of the signs/symptoms of endogenous Cushing’s Syndrome

Role: Co-I

C107-405 Schteingart (PI) 10/18/10 – 10/17/14

Corcept Therapeutics

Corlux compassionate use study

The major goal of this project is to conduct a compassionate use protocol for the administration of mifepristone

in the treatment of the signs/symptoms of Cushing’s Syndrome.

Role: Co-I

Completed Research Support

R01 DK62027 Hammer (PI) 7/01/04-01/31/09

NIDDK NIH Mechanisms of Adrenal Differentiation

The major goal of this project is to determine the unique transcriptional programs in subcapsular

undifferentiated progenitor cells serve to maintain the functional capacity of the adrenal cortex. Our specific

aims in the parent grant are directed towards a systematic characterization of novel functions of SF1 critical to

this process.

NIH R01 DK062027-07S1 Hammer (PI) 01/01/10-04/30/10

NIDDK NIH Administrative Supplement Application for parent grant above (RO1 DK62027)

Funding of the parent grant began February 1, 2009.

University of Wisconsin Jefcoate (PI) 07/22/08-05/31/11

Regulation of StAR Expression and Activated Cholesterol Metabolism Via mRNA 3’UTR

While we continue to address the integration of transcriptional and post-transcriptional control of StAR

expression in adrenal cells, we have focused and reorganized the Specific Aims (see below). The new

proposal builds on recent published progress from other laboratories and on our own new experiments,

particularly on the mechanism of TIS11b. Importantly, we have used a very effective siRNA treatment to lower

the Br-cAMP stimulation of TIS11b by over 80 percent in Y-1 and MA10 cells.

NCI 8199 Hammer (PI) 10/15/08-10/14/12

National Cancer Institute

Multi-institutional phase II study of IMC-A12, a recombinant human IgG1/λ monoclonal antibody directed at the

Type I Insulin-Like Growth Factor Receptor (IGF-1R), in adrenocortical carcinoma: A randomized trial

comparing the activity of IMC-A12 with mitotane versus mitotane alone. Discontinued 06/12.

C1073-400 Schteingart (PI) 06/10/08-06/01/11

Corcept Therapeutics

Corlux study

The major goal of this project is to conduct the clinic trial titled: An Open Label Study of the Efficacy and

Safety of CORLUX® (mifepristone) in the Treatment of the Signs and Symptoms of Endogenous Cushing’s

Syndrome Role: Co-I

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