Jill Bargonetti, PhD

2008-2009 BCRF Project:
(made possible by generous support from Estée Lauder)

Dr. Bargonetti and her colleagues have detected that when estrogen receptor positive breast cancer cells are exposed to estrogen for a prolonged time, the p53 tumor suppressor pathway is compromised in part by the oncogenic protein Mdm2. Over the past year, with BCRF support, they provoked reactivation of some biochemical functions of p53 by disrupting the p53-Mdm2 interaction using the potential chemotherapeutic molecules Nutlin-3, MI-63 and also by siRNA directed at mdm2. However, they achieved the most robust breast cancer cell killing by using a novel inhibitor of RNA synthesis and by a stereo-chemically specific alkylating agent that is able to induce p53-independent cell death by blocking Chk1. Their work suggests that protocols simultaneously activating p53 dependent and p53-independent cell death pathways are excellent therapeutic approaches for killing breast cancer cells.

Dr. Bargonetti's goal for the upcoming year is to design promising protocols to induce death of breast cancer cells by using genetic vectors to block the p53-Mdm2 interaction and/or mutant p53 and to chemically provoke p53-independent death of estrogen-influenced breast cancers. The need to identify drugs, and pathways, that induce cell death independently of p53 activity, or by reactivation of compromised p53, deserves substantial attention. Much still needs to be discovered about the activation of p53-independent cell death and the potential to reactivate p53.

Bio:
Molecular biologist Jill Bargonett is a renowned cancer researcher, and innovator in the education of minorities in science. She was a member of the National Cancer Policy Board from 2002 until 2005 (a board of the Institution of Medicine and National Research Council of the National Academies). Currently a Professor at Hunter College of the City University of New York, Professor Bargonetti has done extensive research on the p53 protein and the p53 gene, which assists in the suppression of tumor cells.

At Hunter's Center for the Study of Gene Structure and Function in the Department of Biological Sciences, she and her colleagues are currently working to determine if tumor promotion in humans results by inhibition of p53 production. They also examine if DNA damage caused by various chemotherapeutic drugs is able to bring about differential activation of p53 target genes as well as activate alternative cell death pathways that may facilitate killing cancer cells. In addition, her research group investigates how an inherited single nucleotide polymorphism (SNP) in the mdm2 gene causes a predisposition to cancer by inactivating the p53 protein while it is associated with DNA in cancer cells.

Prior to arriving on the Hunter College campus in 1994, Bargonetti-Chavarria was a post-doctoral fellow at Columbia University (1990-1994). She was a visiting professor at Rockefeller University in 2002. Jill Bargonetti holds a M.S. and a Ph.D. in Molecular Biology, both from New York University (1987 and 1990 respectively) and a B.A. from SUNY Purchase. Awarded the prestigious Presidential Early Career Award for Scientists and Engineers by President Bill Clinton in 1997, Bargonetti has received numerous research grants from the National Science Foundation and the National Institutes of Health as well as grants from the American Cancer Society and the Department of Defense Breast Cancer Research program.

In 2001, she received a New York City Mayor's Award for Excellence in Science and Technology and an Outstanding Woman Scientist Award from the Association for Women in Science. She also received the 1998 New York Voice Award, given to those who have made a significant improvement to the quality of life in New York City, and the 1997 Kathy Keeton Mountain Top Award from the New York branch of the NAACP. In December 2004, Working Mother magazine profiled her as one of the nation's "Stellar Moms" and in May of 2005 both NYU and SUNY Purchase gave her distinguished Alumna awards.