Institute for Medical Research Israel-Canada, Hadassah Medical School - Hebrew University, Jerusalem, Israel.
Prof. Katzav is the Bernard L. and Mary T. Sachs Professor of Cancer Studies. She earned her Ph.D. at the Weizmann Institute of Science and her post-doctorate at the National Cancer Institute in Frederick, Maryland. Prof. Katzav was a visiting scientist at St. Jude Children's Research Hospital in Memphis, Tennessee and an Associate Professor at McGill University in Montreal, Canada. Since 1995, Prof. Katzav is a member of the Institute of Medical Research Israel-Canada (IMRIC) at the Hebrew University, Jerusalem, Israel.
The main focus of Prof. Katzav’s laboratory is the link between signal transduction and cancer. For that, she is investigating a signal transducer protein, Vav, which is involved in coupling extracellular events to alterations in gene expression in the hematopoietic system. Prof. Katzav discovered Vav when she tested DNA from five esophageal carcinomas for transforming activity. This newly identified gene represented the sixth transforming gene (oncogene) detected in the laboratory and it was designated Vav, the sixth letter of the Hebrew alphabet. Recently, she was the first scientist to demonstrate that Vav plays a major role as an oncogene in human cancer such as neuroblastoma, breast and lung cancer. Vav was also shown to be important for the development of pancreatic cancer. This indicates that Vav can be a promising target protein in anti-tumor therapy.
Prof. Katzav served as the Chairperson of the Research Committee of the Faculty of Medicine (2005-2009). In this capacity, she was responsible for the research activity at the faculty of medicine. This also included allocation of grants to various scientists at the faculty and being responsible in part for the future direction of research. She was also the Chairperson of the Search Committee for recruitment of young academic members ("Vaadat Sinun") and the Chairperson of the Department of Development Biology and Cancer Research at the Faculty of Medicine, the Hebrew University (2009-2014). Prof. Katzav is currently the vice dean of the Faculty of Medicine, the Hebrew University, Jerusalem. She also participated in activities outside the Hebrew University as the Chairperson of several study sections of the Israel Science Foundation and a member of a study section at the Israel Health Ministry.
Pancreatic Ductal Adenocarcinoma (PDAC), the predominant form of pancreatic cancer, develops via acinar-ductal metaplasia (ADM) and neoplastic precursor lesions, such as pancreatic intraepithelial neoplasia (PanIN). Mutant K-Ras is present in >90% of PDAC and represents the most frequent and the earliest genetic alteration found in low-grade PanIN1A lesions. Identification of additional molecular lesions that affect PDAC is of cardinal importance. One such potential protein is Vav1, a hematopietic specific signal transducer. Overexpression of Vav1 is implicated in human PDAC and is indicative of a worse survival rate. We generated transgenic mice that express Vav1, K-RasG12D, or both Vav1 and K-RasG12D (K-RasG12D;Vav1) in the pancreas. The number of lesions in the pancreata of K-RasG12D;Vav1 mice exceeded at least 3 times the number obtained in K-RasG12 mice already at 3-months post transgene induction. Also, the number of Ki-67 (indicative of proliferation) positive cells in K-RasG12D;Vav1 mice was significantly higher than in Vav1 or K-RasG12D transgenic mice. Thus, expression of Vav1 together with K-RasG12D in the pancreas has a dramatic synergistic effect enhancing ADM formation. Also, continuous Vav1 expression is needed for maintenance of the ADM lesions formed. Interestingly, a dramatic increase in phosphorylation of EGFR and activation of Rac1 was noted in pancreatic malignant lesions of K-RasG12D;Vav1 mice compared to the pancreas of the control transgenic mice. These results suggest that Vav1 regulates a cross-talk between tumor cells and the microenvironment resulting in upregulation of signal transduction pathways.
Identification of Vav1 as a protein that synergizes with mutant K-Ras in PDAC development might pave the way to choosing good candidates for therapeutic drug design.