Jill Bargonetti, PhD
New York, New York
Professor, Hunter College
Chair, Molecular, Cellular, and Development PhD Program
Department of Biological Sciences Hunter College Belfer Research Building
Graduate Center, City University of New York
Adjunct Assistant Professor, Weill Cornell Medical College Department of Cell Biology
To develop new ways to target triple-negative breast cancer, an aggressive form of breast cancer, and prevent its growth and metastasis.
Triple-negative breast cancer (TNBC) is a group of diseases that are difficult to treat and have a high likelihood of spreading to other tissues —a process called metastasis. Part of the challenge is that TNBCs currently have few biomarkers that can be used to detect, diagnose, and manage it. TNBCs can evade DNA damaging agents such as PARP inhibitors by adapting their DNA damage repair system—this adaptation often results in genomic instability. Dr. Bargonetti is studying three critical biomarkers—mtp53, MDMX and MDM2—known to drive TNBC and other types of breast cancer to determine their role in this adaptation. Since these biomarkers correlate with increased sensitivity to PARP inhibitors, Dr. Bargonetti’s lab is focused on determining the molecular mechanisms involved in their interaction. These studies will potentially uncover novel ways to exploit the mtp53-MDMX-MDM2 axis and target the breast cancers that use it—thus providing druggable targets in a breast cancer subtype with limited therapeutic options.
Dr. Bargonetti has advanced the understanding of the role mtp53, MDMX, MDM2 in the spread of TNBC. Her work has shown that: 1) metastatic TNBCs that harbor a mutated p53 protein (mtp53) are sensitive to PARP inhibitors; 2) MDM2 and MDMX are often upregulated along with mtp53 in highly metastatic breast cancer; and 3) upregulation of MDMX increases circulating tumor cells (CTCs) thereby facilitating TNBC metastasis. In the last year, the Bargonetti lab demonstrated that PARP inhibition promotes breast cancer cell death and correlates with a progressive reduction in MDMX protein while MDM2 interacts with a critical DNA repair protein. The team has also developed laboratory models in which these proteins have been manipulated in order to delve further into how they influence PARP inhibitor sensitivity.
Dr. Bargonetti and her team will continue to explore the mtp53-MDMX-MDM2 axis as a target for development of novel strategies to accurately identify and kill TNBC cells. Specifically, they will continue to investigate the molecular mechanisms of PARP inhibitor sensitivity driven by these breast cancer biomarkers.
Jill Bargonetti, PhD 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, studying how MDM2 promotes breast cancer proliferation and the survival of circulating tumor cells. She received her B.A. from SUNY Purchase, her MS and PhD from New York University and her postgraduate training from Columbia University. In 1994, she joined the professoriate at The City University of New York (CUNY) at Hunter College and The Graduate Center in the PhD Programs of Biology and Biochemistry and currently holds the title of Full Professor at CUNY along with an adjunct professoriate appointment at the Weill Cornell Medical College in the Department of Cell Biology.
Dr. Bargonetti was awarded the prestigious Presidential Early Career Award for Scientists and Engineers by President Bill Clinton in 1997 and has received research grants from the American Cancer Society, The Department of Defense, The National Science Foundation (NSF), The National Institutes of Health (NIH), and the Breast Cancer Research Foundation (BCRF). 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 served on the NIH Tumor Cell Biology study section from 2012-2018.
The Estée Lauder Companies' Brands Award in Memory of Evelyn H. Lauder
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