Richard G. Pestell, MB, BS, PhD, MD, FACP
Director, Kimmel Cancer Center
Jefferson Chairman Department of Cancer Biology
Vice President for Oncology Services at Thomas Jefferson University Hospitals
2013-2014 BCRF Project:
(The ULTA Beauty Award)
Basal breast cancer includes triple negative breast cancer (TNBC), 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 (i.e. breast tumor initiating cells, BTIC), that may contribute to recurrence and therapeutic resistance. Epithelial mesenchymal transition (EMT) and BTIC are functionally correlated in many cancers. Dr. Pestell’s group has found that DACH1 binds three distinct proteins which regulate EMT (YB-1), BTIC (EYA1) and apoptosis (p53). His team’s research results over the past year lead them to suspect that DACH1 is a breast tumor suppressor. Dr. Pestell will determine the mechanisms by which DACH1 regulates p53. If DACH1 regulates p53 stability, researchers have an additional avenue to enhance therapies for triple negative breast cancer.
Dr. Pestell’s team had previously shown that DACH1 was a key determinant of breast stem cell expansion. They have now shown that the cell fate determination factor DACH1 binds directly to YB1, a protein that induces mammary tumors and epithelial mesenchymal transition (EMT) which correlates with mammary stem cells. The researchers have shown that DACH1 inhibits breast tumor growth and EMT through binding to YB1. We have now shown that DACH1 is phosphorylated and that DACH1 phosphorylation determines whether DACH1 can block YB1 and EMT. As DACH1 inhibits breast cancer stem cell expansion, which plays a role in metastasis and therapy resistance, the mechanisms governing DACH1 phosphorylation may be a key new therapeutic target to suppress breast cancer stem cells.
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 more than 620 published works, including more than 400 original publications and book chapters and more than 200 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, with approximately 35,400 citations and an H-index of 97.
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.
Dr. Pestell was born in Perth, Western Australia, and has two sons.