Alexander Levitzki

The Hebrew University of Jerusalem


Primary Section: 41, Medical Genetics, Hematology, and Oncology
Secondary Section: 21, Biochemistry
Membership Type: International Member (elected 2017)

Biosketch

Alexander Levitzki was born in Jerusalem and studied chemistry and microbiology at the Hebrew University of Jerusalem where he received his M.Sc degree in 1963. He then served in the army and went to graduate for his PhD at the Weizmann Institute of Science in Rehovoth. He developed polyhistidine/Cu as a model for oxidases and published his work (with I. Pecht) in Nature. He then went to the University of California, Berkeley to work with Daniel E. Koshland, Jr. with whom he made seminal contributions to the studies on allosteric enzymes. In 1971 he assumed a faculty position at the Weizmann Institute where he received tenure in 1974. At the Institute the Levitzki laboratory continued to make seminal contributions to the field of allosteric regulation and began his work on signal transduction of G protein coupled receptors. In 1975 Levitzki moved the Hebrew University and continued the research he began at the Weizmann Institute on the beta-adrenergic receptor and its mode of coupling to Gs. In his laboratory in Jerusalem Levitzki is working on the development of various cancer therapies using small molecules and vectors that target PolyIC to the tumor, thus recruiting the immune system to attack the tumor.

Research Interests

Alexander Levitzki is recognized for his contributions to enzymology, signal transduction and signal transduction therapy. Initially he became known for his work on the allosteric regulation of regulatory enzymes. He developed methods to study coopertaivity and the phenomenon of half-of-the-sites reactivity. He later moved to the study of the mode of coupling of beta adrenergic receptors with G proteins. In this field he has shown that one receptor can activate many adenylyl cyclase molecules ('collision coupling”), and that the Gs protein remains associated with the enzyme throughout the cycle with no loss of the beta-gamma subunits. Genetic studies on the G protein of the mating system of S.cerevisiae confirm that the G protein remains intact during the activation cycle. In parallel to these studies the Levitzki laboratory became known to generate the first tyrosine phosphorylation inhibitors (Tyrphostins, TKIs) that do not inhibit Ser/Thr kinases. The Levitzki laboratory was the first to generate inhibitors for EGFR, PDGFR, VEGFR2, Bcr-Abl and Jak2. This work stimulated the development of Gleevec and 15 other kinase inhibitors, used in the clinic with dozens in development. Recently he developed an IGF1R/Stat3 dual inhibitor for that inhibit the tumor as well as the tumor microenvironment. In parallel, since 2006 the Levitzki laboratory develops vectors that deliver polyinosine/polycytosine (PolyIC) to tumors.

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