Rachel Hazan, PhD
Bronx, New York
Professor of Pathology
Albert Einstein College of Medicine
Bronx, New York
Understanding what drives tumor growth and survival in order to prevent the spread of breast cancer.
Metastasis—the spread of tumors to other tissues—is the main cause of death from breast cancer. While treatable, metastatic breast cancer is currently incurable. Metastasis is a complex, multi-step process. For tumors to metastasize, cancer cells must travel through the bloodstream or lymphatic system. The mechanisms that give cancer cells the ability to travel through the body and colonize new sites, however, are largely unknown. Dr. Hazan seeks to uncover how cancer cells acquire the ability to spread to ultimately reveal new therapeutic strategies to prevent metastasis from occurring.
Dr. Hazan has shown that an enzyme called glutathione peroxidase 2 (GP2) is a strong inhibitor of metastasis. The loss of GP2 activity in breast cancer has been shown to be associated with short-term survival of breast cancer patients. Dr. Hazan discovered that loss of GP2 function in breast cancer cells renders them highly metastatic. In the past year, Dr. Hazan uncovered a certain kind of tumor cell type that may contribute to metastasis, and hence to a worse clinical outcome. She and her team found a virulent cancer cell state that appears to be exacerbated by GP2 loss in breast cancer. They also found that GP2 loss activates a molecule known as hypoxia inducible factor alpha (HIF1a) which might promote this aggressive state of cancer cells.
In the upcoming year, Dr. Hazan is working to further understand the aggressive state of cancer cells. She and her team will better characterize this state by determining how enriching or repressing this cell state modulates circulating tumor cells that seed new metastases and other factors that drive metastasis. Dr. Hazan will also determine whether targeting HIF1a suppresses the metastatic behavior of breast cancer cells. This information is vital for improving the likelihood of developing novel therapeutic approaches to combat breast cancer metastasis.
Dr. Rachel Hazan received her PhD from George Washington University in 1990. She performed her thesis work under Dr. Joseph Schlessinger, where she studied Her2 signaling in breast cancer, and was the first to map Her2 phosphorylation sites. She then joined Dr. Gerald Edelman, a Nobel laureate at Rockefeller University and Scripps Research Institute to study adhesion molecules and their regulation in neuronal and epithelial cells. This served as a basis for her ongoing work on cadherin adhesion molecules and their role in breast cancer dissemination. In 1994, she joined Memorial Sloan Kettering Cancer Center, where she initiated seminal studies on the role of cadherin switching in breast cancer progression. In 1997, she became Assistant Professor at the Mount-Sinai School of Medicine, and is presently Professor of Pathology at the Albert Einstein College of Medicine. Dr. Hazan has been studying the role of adhesion in invasion and epithelial to mesenchymal transition leading to metastasis. She showed that N-cadherin activates cancer spread by sustaining activation and signaling of the Fibroblast Growth Factor Receptor. Dr. Hazan discovered a variety of signaling pathways that contribute to metastasis and has so far elucidated key signaling modules including the MAPK, AKT and cell cycle regulators as critical promoters of metastasis. Her work uses laboratory models, cell culture systems and validation in clinical breast specimens. These models serve as a platform to elucidate mechanisms of metastatic spread with the goal of identifying pivotal targets for therapeutic application.
The Neil and Jane Golub Award
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