Hammer Laboratory

Dr. Hammer lives in Ann Arbor with his wife Lisa Hammer, M.D.
and their three children Maggie, Max, Zach and their dog Bella.

 

 

Gary D. Hammer, M.D., Ph.D.

Other Useful or Interesting Information

 

LABORATORY INFORMATION

Research projects in my 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 that target the molecular defects in stem cells while sparing normal tissue.

CLINIC INFORMATION

As the Director of the Endocrine Oncology Program in the Comprehensive Cancer Center at the University of Michigan, I hold the Millie Schembechler Professorship in Adrenal Cancer. Under my leadership, the Program was selected as one of five inaugural Destination Programs singled out for research and clinical excellence at the University of Michigan Health System. The Program is uniquely recognized as an international center of excellence for the treatment of adrenal cancer.

CENTER FOR ORGANOGENESIS

I am also the newly appointed 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.

 

 

Short Research Statement

My research focuses on the molecular underpinnings of adrenocortical growth in development and cancer. My laboratory's goals are to characterize the adrenocortical stem/progenitor cell population and elucidate how altered regulation of these cells contributes to adrenocortical disease, namely hypoplasias, dysplasias and cancer. Classic molecular approaches to signaling and transcriptional activation are combined with whole animal biology to examine adrenocortical development and function as it pertains to human disease. My laboratory has shown that the orphan nuclear receptor SF-1 (steroidogenic factor-1) is absolutely required for proliferation of the adrenocortical stem/progenitor cells while the orphan receptor Dax-1 serves to maintain the multipotency of these cells in vivo. Moreover, my group has provided a novel paradigm by which a key stem cell renewal pathway (Wnt signaling) can influence nuclear receptor function, namely that beta-catenin can directly bind and activate SF-1 mediated transcription in the adrenal cortex. Targeted loss- and gain-of-function of canonical Wnt signaling results in loss and expansion of adrenocortical stem/progenitor cells and ultimate adrenal failure and adrenal cancer, respectively. Ongoing molecular studies detail the mechanisms by which such membrane-initiated signals mediate the cyclic entrainment of SF-1 transcription complexes - predicting a unique layer of regulatory control common to multiple classes of transcription factors. Work on inhibin null mice has unraveled a unique role of inhibin as a gatekeeper of adrenal versus gonadal differentiation in the adrenal gland. In the absence of adrrnal inhibin, unopposed TGFb2/Smad3 signaling in the adrenocortical stem/progenitor cell results in uncontrolled stem/progenitor cell expansion and ultimate differentiation into ovarian tissue. The positional cloning of the mutation responsible for adrenocortical dysplasia in mice by my group has provided clues to the role of telomere maintenance in these cells. As this gene was simultaneously described as a telomere regulatory protein, this is the first characterization of a viable tissue-specific defect in a mouse with a mutation in such a regulatory gene. Because Wnt signaling and telomere biology are intimately involved in stem/progenitor cell biology, my lab's current efforts are heavily weighted towards understanding the signaling and transcriptional mechanisms involved in the regulation of adrenocortical stem/progenitor cells in development and cancer. With U-M collaborators, my lab is also investigating how gene profiles can be used to diagnose adrenal cancer or predict how well a patient will respond to treatment. I hope to develop new treatments, including targeted biological-based therapies designed to hone in directly on the cancer cells while sparing normal tissue. A national NCI-sponsored trial using a monoclonal antibody to the IGF1R receptor is my labs first of such therapies for adrenal cancer.