About Us & Contact Information

Dr. Gary Hammer's research focuses on the molecular underpinnings of adrenocortical growth in development and cancer. His 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.

Dr. Hammer's Contributions to Science

ADRENAL STEM CELLS, DEVELOPMENT AND HOMEOSTASIS 

Dr. Hammer defined adrenal stem and progenitor cells and the key signaling and transcriptional programs that control their self-renewal, multipotency, and differentiation. His lab redefined the adrenal cortex’s zonal structure (zG, zF, zR), showing it to be more heterogeneous than previously thought. He identified a progenitor cell population beneath the adrenal capsule and mapped the SHH-Wnt signaling relay that governs their fate. His work also revealed that CDK7-mediated phosphorylation of SF1 drives SHH progenitor differentiation into zG cells and that Wnt signaling enables the zG-to-zF cell transition. He demonstrated that Dax-1, regulated by Wnt and glucocorticoids, maintains progenitor cell identity. Clinically, he linked Dax-1 mutations to adrenal hypoplasia and Wnt2B loss to isolated zG failure.

ADRENOCORTICAL CARCINOMA (ACC)

Under Dr. Hammer’s leadership, the program has been singled out for research and clinical excellence at the University of Michigan Health System. The program is recognized as an international center of excellence for the basic-translational-clinical study and treatment of adrenal cancer.

SIGNALING/TRANSCRIPTION/BIOCHEMISTRY

Dr. Hammer’s work on SF1 activation transformed the understanding of orphan nuclear receptor function. His studies on sumoylation and CDK7-mediated phosphorylation revealed how dynamic signaling regulates adrenal cell proliferation and differentiation. He was the first to show cyclic transcriptional regulation of a nuclear receptor via phosphorylation and sumoylation. His lab also played a key role in launching the TCGA-ACC project and pan-cancer analyses of oncogenic signaling. Additionally, mouse models from his group uncovered novel mechanisms of telomere protection and paracrine hormone (e.g., inhibin) regulation in adrenal homeostasis and disease.

TRANSLATIONAL / CLINICAL GENETICS

Dr. Hammer has directed several landmark genomic studies of adrenal cancer that have defined critical signaling pathways involved in the disease's biology. Constitutive activation of Wnt signaling (and hence Dax1) leads to progenitor expansion and the development of adrenal cancer in both mice and humans. With Wnt and IGF signaling being essential pathways for maintaining stem cells, the Hammer lab has defined these pathways as critical initiators of human adrenal cancer – data that Dr. Hammer has used to launch national and international clinical trials for adrenal cancer. For these patients, this is a first in 50 years.

CLINICAL TRIALS / THERAPEUTICS

Dr. Hammer has served as an international PI on both investigator-initiated and industry-sponsored trials for adrenal disease. He has also founded two biotech companies, Millendo and Sling Therapeutics, that focus on rare endocrine/adrenal diseases.