Ph.D. Weizmann Institute of Science, Rehovot, Israel
Post-doctorate, National Cancer Institute, Frederick, Maryland, USA
Scientist Associate, National Cancer Institute, Frederick, Maryland, USA
Visiting Scientist, St. Jude Children’s Research Hospital, Memphis, Tennessee, USA
Associate Professor, Faculty of Medicine, McGill University, Montreal, Canada
Associate Professor, Faculty of Medicine, Hebrew University
Bernard L. & Mary T Sachs Chair in Cancer Research
Tasks at the Hebrew University in recent years:
Chairperson, Department of Experimental Medicine and Cancer Research
Chairperson of the Research Committee of the Faculty of Medicine.
Member of the Research Committee of the Hebrew University.
Member of the Senate of the Hebrew University.
Chairperson of the Search Committee of the Faculty of Medicine for academic members ("Vaadat Sinun").
Chairperson of the Department of Developmental Biology and Cancer Research.
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Vav1, an oncogene and a signal transducer protein
My research focuses on discovering the links between the signaling pathways within cells and the transforming processes that cause cancer. Cell behavior, including growth, survival and motility, is regulated by a complex network of intracellular and extracellular signal transduction pathways. There is great interest in identifying and characterizing the components of these signaling pathways, and learning how they go awry in disease states. Cancer is often associated with mis-regulated signal transduction, frequently stemming from mutated versions of normal (onco)genes and tumor suppressor genes. It is therefore critical to learn more about the normal and abnormal function of these signal transduction molecules.
Vav1 is one important example of a signal transducer protein involved in cancer. While working in Dr Mariano Barbacid’s laboratory, I identified Vav1 in a screen for oncogenes in which NIH3T3 cells were transfected with DNA from several esophageal carcinomas. Nucleotide sequence analysis revealed that the Vav oncogene was activated in vitro. Since Vav was the sixth oncogene detected in Dr. Barbacid's laboratory it was designated Vav, the sixth letter of the Hebrew alphabet.
I subsequently identified its wild-type form, now termed Vav1. It is now clear that Vav1 is an important signal transducer with a pivotal role in the hematopoietic system, in which it is exclusively expressed. My research has made a major contribution to the identification, characterization and understanding of the physiological role of Vav1 in hematopoietic cells. Elimination of Vav1 in the mouse genome leads to faulty functions and impaired development of the immune system, highlighting its physiological importance. I have shown that Vav1 encodes a unique protein with several modular motifs known to play a role in tyrosine mediated signal transduction. Activation of Vav1 leads to cytoskeletal rearrangement during activation of hematopoietic cells, an event critical for numerous cell functions.
|Vav1 and Signal Transduction Pathways in T Cells.
||Changes in Cytoskeleton Organization following Overexpression of Vav1.|
Until recently, the Vav1 oncogene had not been detected in human cancer. Thus, although truncated versions of Vav1 lacking the amino terminus transform NIH3T3 fibroblasts and synergize with active Ras in transformation, their role in human tumorigenesis was disputed. My laboratory was the first to demonstrate that ectopic expression of wild-type Vav1, not its mutant form, is involved in human malignancies, strongly suggesting that Vav1 contributes to the neoplastic process in a subset of neuroblastomas. We have since demonstrated that Vav1 is involved in human lung cancer, a malignancy which is the leading cause of cancer death worldwide, as well as in human breast cancer.
Our results suggest that Vav1 plays a role in the neoplastic processes, identifying it as a potential therapeutic target for cancer therapy.
Knock-down of Vav1 in Cancer Cells Inhibits Tumor Progression and Restores Normal Cytoskeleton Organization.
· The role of Vav1 and its responsive genes in lung cancer development-using in vitro and in vivo mouse transgenic models
· Vav1 in Pancreatic Cancer
· The role of Vav1 and its responsive genes in breast cancer development-using in vitro and in vivo mouse transgenic models