Rachel Hazan, PhD

2009-2010 BCRF Project:
The First Step Award, made possible by generous support from QVC and the Fashion Footwear Charitable Foundation
Co-Investigator: Larry Norton, MD, Memorial Sloan-Kettering Cancer Center, New York, NY

Aggressive breast cancers abnormally express the cell-cell adhesion molecule N-cadherin, and Dr. Hazan and her colleagues showed that this expression stimulates metastasis although it reduces primary tumor growth. This relationship implies that N-cadherin targeted therapies might eradicate metastasizing cells and be useful at a clinically intractable stage. New data suggest that N-cadherin induces a phenotypic switch to an aggressive phenotype, known as epithelial to mesenchymal transition, due to activation of the FGF receptor signaling pathway, leading to the expression of transcription factors, which render cells metastatic. Dr. Hazan proposes to investigate this relationship and evaluate available drugs that may disrupt the cooperation of N-cadherin with the FGF receptor as a therapeutic modality for metastasis. The information gained will have important clinical implications for treatment of late-stage breast cancer.

Bio:
Dr. Rachel Hazan received her PhD from George Washington University in 1990. She accomplished her thesis work in the laboratory of Dr. Joseph Schlessinger where she studied the role of Her2/neu signal transduction in breast cancer. During this work, she characterized the tyrosine phosphorylation sites on Her2/neu and generated a panel of monoclonal antibodies against HER2/neu which were successful in suppressing breast cancer cell growth and transformation.

She then joined the laboratory of Dr. Gerald Edelman at Rockfeller University and Scripps Research Institute as a postdoctoral fellow to learn about adhesion molecules which were just beginning to be implicated in cancer progression. This background served as a basis for her current work in which she is investigating how cadherin adhesion molecules and growth factor receptors cooperate in tumor metastasis.

In 1994, she joined the department of Surgery at Memorial Sloan-Kettering Cancer Center as an Assistant Laboratory Member and initiated work on the role of adhesion molecules in breast cancer. In 1997, she joined Mount-Sinai School of Medicine as an Assistant Professor and in 2003 the Albert Einstein College of Medicine as Associate Professor of Pathology.

Dr. Hazan found that a neural cadherin, N-cadherin was overexpressed in most invasive and metastatic human breast cancer cell lines and tumors. N-cadherin induces metastasis due to its ability to bind and potentiate signaling by the FGF receptor. She is currently pursuing the genes and downstream signaling pathways that are promoted by the N-cadherin-FGFR axis as well as how N-cadherin adhesive interactions with the host microenvironment also play a role in tumor dissemination. Her current studies involve the use of transgenic breast cancer mouse models in which mammary co-expression of N-cadherin with the PyVmT antigen or the Her2/neu oncogene were found to dramatically increase the metastatic potential of breast cancer cells. These models will serve as a basis to determine the molecular mechanisms underlying N-cadherin metastatic activity and identify targets for translational or therapeutic application in breast cancer.