Prof. Arthur Gutierrez-Hartmann
Arthur Gutierrez-Hartmann completed his MD degree at the University of Texas Southwestern Medical School (UTSW) in 1975. From 1971-1977, he also pursued graduate studies purifying yeast mitochondrial citrate synthase in Dr. Ron Butow’s lab at UTSW.
Arthur completed Internal Medicine residency training at Stanford University Hospital (1977-1980), and then pursued a Molecular Endocrinology training fellowship with Dr. John Baxter at UCSF (1980-83). Dr. Chip Ridgway recruited Arthur to the University of Colorado HSC in 1985, where Arthur was a founding member of the MST Program (1985), the Molecular Biology Graduate Program (1986), the Cancer Center (1987), and the Physician-Scientist Training Program (2011).
Arthur has served on the Advisory Committee of the NIH Director, Task Force on the Future of the Biomedical Workforce, Council of the American Cancer Society (ACS) and NIGMS, and he serves on multiple editorial boards. Arthur has been selected for many awards and visiting professorships, including: an A. P. Giannini/Bank of America Fellowship (1980-1982); a PEW Scholar Award in the Biomedical Sciences (1986-1990); elected to the American Society of Clinical Investigation (1992) and Association of American Physicians (2012); the 2002 SACNAS Distinguished Scientist of the Year Award; the 2008 AACR Jane Coffin Wright – Minority in Cancer Research Award; the 2009 Endocrine Society’s Distinguished Educator Award; and the inaugural ASBMB 2010 Ruth Kirchstein Diversity in Science Award.
The main focus of my laboratory is to determine the role of Ras/MAPK signaling and ETS transcription factors in epithelial cell development and tumorigenesis, with a focus on pituitary, mammary and GI model systems. With regards to the pituitary project, over the past 30 years, we have studied how the combinatorial action of ETS factors, acting in concert with the POU-homeodomain transcription factor, Pit-1, serve to regulate the lactotrope-specific basal and Ras-regulated expression of the prolactin gene. Utilizing biochemical, structural, molecular and transgenic approaches, we have discovered that ETS factors play a critical role in specifying lactotrope cell identity in pituitary ontogeny.
Currently, we are focusing on the roles of PI3K and menin in regulating lactotrope proliferation. We began studying breast cancer in 2002, using in vitro and in vivo approaches to elucidate the role of the epithelial-specific ETS transcription factor, ESE-1, in human mammary epithelial cell tumorigenesis. With DOD Breast Cancer grant support, we discovered a novel nongenomic, cytoplasmic mechanism by which ESE-1 initiates transformation in immortalized, but nontransformed MCF-12A human mammary epithelial cells. Focusing on established luminal, HER2+ and triple-negative breast cancer cell lines, we find that they gain ESE-1 expression in the nucleus, and we have demonstrated that ESE-1 is required in breast cancer cells to maintain the transformed state by using shRNA knockdown. Importantly, we’ve generated highly-specific mAbs targeting ESE-1, which work well in multiple assays (WB, IF, ICC, IHC, IP, and ChIP).
We’ve used these MAbs in collaborative IHC studies of breast cancer specimens (Ann Thor and Susan Edgerton), and found that increased ESE-1 levels correlate with poor clinical outcomes. Currently, we’re working with Dr. Mark Borden, in Mechanical Engineering at CU-Boulder, to use ultrasound-mediated delivery of siRNA-loaded microparticles to target ESE-1 as a means to treat breast cancer. In the GI project, we have used transgenic approaches to show that ETS factors are critical for enterocyte differentiation and, surprisingly, that ETS factors function as tumor suppressors, rather than tumor promoters, in this system.
See complete list of published work in MyBibliography: