Dr. Gary D. Hammer, M.D., Ph.D., is a medical endocrinologist specializing in the treatment of adrenal disease.  Research projects in his 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.  Adrenocortical carcinoma (ACC) is a very rare endocrine cancer (1-2/million population/year) but its importance is magnified by its dismal prognosis, lack of therapies with proven efficacy and its association with several genetic syndromes.

Adrenal cancer and adult stem cell maintenance and dysregulation.  Cancer results from mutations in specific genes that participate in a variety of signaling pathways that normally control the growth of cells within a given organ.  Research is beginning to uncover the specific aberrant pathways that are defective in individual cancers and the unique cells in which such aberrant signaling initiates the oncogenic transformation.  It has recently become established that the continued growth maintenance of any organ is mediated by the presence of tissue (adult) stem cells (ASCs) within the organ. Recent developments indicate that many, if not all, cancers are caused by defects within these organ‑specific ASCs  that become dysregulated cancer stem cells.  Understanding how such cancer stem cells arise and proliferate indefinitely is considered a most critical “next step” in finding effective cures for cancer.  While most cytotoxic chemotherapies are effective at killing 99.99% of the cells within a tumor, current data suggests that the therapy does not target the stem cells that remain in the patient, preventing cure and allowing for frequent cancer recurrences.

Growth Factor Signaling: Current research aims to understand the signaling pathways that control normal ASCs and how perturbation of such pathways allows such cells to escape regulatory control * resulting in a rouge cancer stem cell and ultimately cancer.   Such information is deemed critical to finding effective treatments that target the actual defective pathways that contribute to cancer.  Indeed, in many cancer types ‑ both familial and sporadic ‑ pathways such as the Wnt and IGF pathways are constitutively active and have been proven to be critical for both ASC survival and cancer initiation or maintenance ‑ lending credence for targeted (“biologically based”) therapies aimed at these signaling pathways in cancer stem cells.  Research efforts include basic and translational (“bench‑to‑bedside”) studies together with clinical trials with compounds that specifically inhibit these pathways unique to the cancer stem cell to ultimately find effective cures for cancer.

Wnt signaling

Telomeres and Telomerase: Telomeres are the far ends of chromosomes and in normal cells telomeres shorten with each cell division allowing appropriate cell aging.  Stem cells and most cancer cells have mechanisms that maintain telomere length and allow indefinite cell expansion.  Telomerase is an enzyme that is critical in this process of stem cell and cancer stem cell “immortality."

Transcription factors and transcriptional regulation:  The objective of this area of research is to understand the biochemical mechanisms by which cell-type specific transcription factors direct the differentiation of adrenocortical cells within the adrenal gland.  The focus has been on the nuclear receptors Sf-1 and Dax-1.