Richard G. Pestell, MD, PhD
Director, Kimmel Cancer Center
2012-2013 BCRF Project:
(made possible by generous support from ULTA Beauty)
Jefferson Chairman Department of Cancer Biology
Vice President for Oncology Services at Thomas Jefferson University Hospitals
Breast cancer is the second most prevalent cancer-related death in women in the United States. Basal breast cancer includes triple negative breast cancer, defined by the absence of three receptors (estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 [HER2]). Triple negative breast cancer is prominent among African-American women, and currently no targeted therapies for this type of breast cancer exist. Within human breast cancer a subset of cells have characteristics of stem cells (BTIC), which may contribute to recurrence and therapeutic resistance. The mechanism by which the gene DACH1 inhibits BTIC is being determined as a new approach to enhance therapeutic responsiveness. Dr. Pestell's findings over the last year that DACH1 binds to and enhances function of the p53 tumor suppressor, but fails to bind mutations of p53 identified in human breast cancer, adds further weight to the original hypothesis that DACH1 is a breast tumor suppressor. Dr. Pestell's studies in 2012-2013 will continue to define the role of endogenous DACH1 as a breast cancer suppressor.
Mid-year Progress: Dr. Pestell's team attempted to identify a tractable therapeutic target by identifying a biochemical activity associated with DACH1. Eya1 is a phosphatase that they have now shown binds directly to DACH1, representing a tractable biochemical target. The mechanisms by which DACH1 inhibits BTIC via EYA1 are being determined as a new approach to enhance therapeutic responsiveness. Dr. Pestell's team will continue to determine the mechanisms by which DACH1 regulates p53. If DACH1 regulates p53 stability, scientists have an additional avenue to enhance therapies potentially for triple negative breast cancer. also It is also vital to understand the significance of the different expression patterns for EYA1 vs DACH1 in different genetic subtypes of breast cancer as it may affect precision treatment of genetic subtypes of human breast cancer.
Dr. Pestell's research has made significant contributions to understanding cell cycle regulation and the aberrations that can lead to cells turning cancerous. His laboratory was the first to show that nuclear receptors (estrogen and androgen receptors) are acetylated, and that this event is rate-limiting in hormone signaling and growth control- thus a new target for cancer therapy. His laboratory demonstrated that this was a general mechanism conserved among nuclear receptors that affect diverse biological processes. In the cell cycle field, Dr. Pestell's research has shown: the discovery that cyclins are direct transcriptional targets of oncogenic and tumor suppressor signals. That cyclin expression is rate-limiting for oncogene-induced breast tumor growth in vivo and that cyclin D1 regulates diverse function including cellular migration, mitochondrial metabolism, angiogenesis, and nuclear receptor function in vivo. In breast cancer stem cell research, his laboratory was the first to define key target genes required for breast cancer stem cell expansion in vivo including p21CIP1, c-Jun, the canonical NFkB pathway and the cell fate determination pathway protein Dach1.
Dr. Pestell has authored 372 original publications and book chapters and 190 published abstracts. His papers have been published in journals including Cell, Science, Nature Medicine, Molecular Cell, and European Molecular Biology Organization Journal. His work is well cited (>30,000 citations).
Dr. Pestell received his M.D. (1981) and Ph.D. in Australia where he completed Oncology and Endocrinology training. As recipient of the Royal Australian College of Physicians Winthrop and Neil Hamilton Fairley awards (1991-1994) he continued research at Harvard University and was a Clinical Fellow at Massachusetts General Hospital. From 2002 he served as Chairman of the Department of Oncology, Charlotte Gragnani Endowed Chair, Director of the Lombardi Cancer Center and Associate Vice President of Georgetown University Medical Center. From 2005 he has been Director of the Kimmel Cancer Center, Associate Dean and Vice President Oncology Services, Thomas Jefferson University and Hospitals, Philadelphia. The Jefferson Cancer Network includes 22 hospitals in the USA Northeast. He is past President of INCTR (USA), and was the founding Director of the Delaware Valley Institute for Clinical and Translational Science (2008).
Some of Dr Pestell's recent awards for his scientific discoveries in breast and prostate cancer including elected membership to the American Society of Clinical Investigators, Fellow of the Royal Society of Medicine, the Irma T. Hirschl Weil Caulier Career Scientist Award, Diane Belfer Faculty Scholar in Cancer Research, Gragnani endowed Chair, the Pfeiffer Award, the Harrison award, (the highest award of the Australian Endocrine Society), the R.D. Wright medal, Komen Light of Life award, a Doctorus Honoris Causa, and the Raine Distinguished Professor. Dr Pestell serves as a reviewer for 11 funding agencies and has been an active member of NIH study sections (RO1, SPORES, Cancer Centers, Program projects). He serves as scientific advisory board member to 7 NCI Cancer Centers and many Funding agencies. Dr Pestell has been a reviewer for 18 distinct scientific journals, has served on editorial boards of 6 journals and founded 3 Biotechnology companies.
Born in Perth Western Australia he is married and has two sons.