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Jill Bargonetti, PhD

Professor, Department of Biological Sciences
Hunter College, City University of New York
New York, New York

Current Research

  • Studies are focused on identifying new therapeutic approaches in advanced breast cancer.
     
  • A new combination approach is being tested in triple negative breast cancer, while new targets are explored in estrogen receptor-positive breast cancers.
     
  • This work can have significant impact in expanding the use of PARP inhibitors to more TNBC patients.

PARP inhibitors are a class of drugs that specifically target cells with defects in DNA repair processes. Many triple negative breast cancers fall into this category. TNBC also frequently harbor mutations in the p53 gene and Dr. Bargonetti has found that TNBC with mutant p53 are very sensitive to PARP inhibitors. She is looking for ways to identify these cells in tissue and blood to more accurately target them for more personalized therapy for all breast cancer types. 

Full Research Summary

Dr. Bargonetti’s research focuses on three of the most critical proteins that promote different subtypes of breast cancer. These proteins carry mutations in the genes encode for p53 (mtp53), MDM2, and MDMX, all which drive triple negative breast cancer (TNBC). In addition, MDM2 also drives estrogen receptor (ER) positive breast cancers. 

In normal cells p53 is not mutated and levels of MDM2 and MDMX are kept low. In breast tumor cells and highly metastatic breast cancers, p53 is often mutated, and MDM2 and MDMX are overexpressed.  

In earlier work, Dr. Bargonetti and colleagues discovered that metastatic TNBC that harbor a mutation in p53 are sensitive to PARP inhibitors, a class of drugs that target cells with deficient DNA repair. One form of the drug called olaparib (Lynparza®) was recently approved for treatment of advanced BRCA breast cancers, many of which are triple negative. 

Her team is testing a novel approach that couples the mutant p53 biomarker to PARP inhibitors in a combined platform for diagnostics and therapeutics for TNBC.

The Bargonetti team is determining ways to accurately image tumors and liquid biopsy material to identify and kill cells with mutant p53 and high levels of MDM2 and MDMX.  They are studying the roles of mtp53, MDM2, and MDMX in metastasis and proliferation of the different subtypes of breast cancers and will determine how to best target these pathways for improved cancer cell death. 

Their ongoing research is geared to discover personalized therapeutic strategies for mtp53, MDM2, and MDMX driven breast cancers. 

Biography

Dr. Bargonetti began at Hunter College as an Assistant Professor in 1994 and is currently a Full Professor and the Chair of the Molecular, Cellular and Developmental PhD Subprogram in Biology at the CUNY Graduate Center. Professor Bargonetti has carried out extensive research on the wild-type p53 protein (which assists in the suppression of tumor cells) and oncogenic mutant p53 (which is a tumor promoter). She is also a leader in the field of MDM2 research concerning its involvement in the promotion of breast cancer through both chromatin-based inhibition of the p53 pathway and cell growth promotion through p53-independent mechanisms. 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) and currently serves on the NIH Tumor Cell Biology study section.

BCRF Investigator Since

2005

Area(s) of Focus