NYU School of Medicine
New York, New York
Professor, Department of Radiation Oncology
Professor of Microbiology
Co-Director, Breast Cancer Research Program
Albert B. Sabin Professor of Molecular Pathogenesis
Understanding the underlying biology driving breast cancer metastasis and identifying molecular targets for the development of effective therapies to reduce breast cancer deaths.
Breast cancer metastasis, the spread of cancer from the original site to other parts of the body, is a complex and multi-step process. While metastatic breast cancer is treatable, it cannot be cured and is responsible for most deaths due to breast cancer. This makes the development of new therapeutic strategies an urgent priority for researchers such as Dr. Schneider. He was the first to recognize the importance of the protein synthesis machinery to the growth and metastasis of breast cancer cells and has been building on this finding to develop new methods to target protein production in metastatic breast cancer cells. His team has identified key pathways in this process and have developed several experimental drugs to selectively inhibit them. Dr. Schneider discovered a factor called DAP5, one part of a complex of factors involved in the synthesis of proteins necessary for tissue invasion, cell detachment, and migration—key processes required for metastasis. DAP5-mediated metastasis utilizes a mechanism of protein synthesis not previously described and the team has identified an essential protein component of the DAP5 complex, called eIF3d, which interacts with DAP5 to mediate these processes.
Using dynamic structural prediction models, Dr. Schneider and his team have initiated studies to determine how DAP5 and eIF3d interact and to design small molecules that can inhibit this process. In the last year, they showed that DAP5-eIF3d controls the synthesis of proteins that promote cell migration, invasion, and metastasis. They also developed laboratory models to represent different stages of breast cancer from development to metastasis and used them to assess the effects of small molecule inhibitors on the metastatic process. In other studies, his team is exploring how specific immune cells, known as regulatory T cells (Tregs), are actively recruited by tumors shielding the tumor cells from an anti-tumor immune response. Dr. Schneider has found that Tregs use a novel mechanism to produce their essential proteins and blocking this mechanism not only hinders the tumors’ ability to suppress the immune system, it reverts Tregs to tumor killing T cells.
Moving forward, Dr. Schneider and his team will continue to study how the DAP5-eIF3d complex promotes breast cancer metastasis and to test the small molecule inhibitors they have developed. Ongoing investigations will aim to develop other agents that target this complex and test their ability to both treat and prevent metastasis in laboratory models. In addition, they will focus on the mechanism by which DAP5-eIF3d mediates Treg action and how manipulation of DAP5-eIF3d activity can be exploited to impair Treg cell immune suppression and improve the efficacy of anti-PD1 therapy. These laboratory studies will inform strategies to block the immunosuppressive action of Tregs and may be clinically relevant for the treatment of metastatic breast cancer.
Robert J. Schneider, PhD is the Albert Sabin Professor of Molecular Pathogenesis at NYU School of Medicine, an Associate Director of the NYU Cancer Institute, Breast Cancer Program Co-Director and Associate Dean for the Office of Therapeutics and Industry Alliances. He has published more than 140 peer reviewed papers. His research is directed to the development, progression and metastasis of breast cancer and the interplay of the inflammatory response, and the development of new therapeutics for metastatic breast cancer.
Dr. Schneider has received numerous awards and prizes in recognition of his research, including the 2010 Judah Folkman Memorial lecture; the 2011 Distinguished Alumnus Award & Commencement address, University of Delaware and the 2012 Susan E. Donelan Hope for the Future Award for breast cancer research, Dana Farber Cancer Institute. Dr. Schneider is a founding scientist of five biotechnology companies focused on translating oncology research to the clinic.
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