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Dr. Karin Halevi-Tobias

Karin holds a Ph.D. degree in Molecular Biology from the Weizmann Institute of Science Rehovot. Her Ph.D. thesis, in the field of molecular and cellular biology, focused on the proto-oncogene c-Myc as a transcription factor and inducer of apoptosis and on the control of c-Myc degradation. She worked for more than ten years in biotechnology start-up companies in the fields of drug discovery and drug development. Karin joined IMBM in January 2008.

Scientific activity in 2010

Over the past year, Karin has been involved in two research topics:

Development of a general algorithm for in-treatment guidance of individualized therapy, based on validated mathematical models. The algorithm, tested for PCa vaccination therapy, showed that clinical data collected early in treatment suffice for calibrating and verifying a reliable patient–tailored model. The model can predict treatment outcomes and search for more effective therapeutic protocols in a patient–specific manner. This work was done with Yuri Kogan, Moran Elishmereni and Zvia Agur from IMBM and Stanimir Vuk-Pavlović from Mayo Clinic, Rochester, USA.

Development of a mathematical model for the Wnt signaling pathway, from receptors binding down to ß Catenin accumulation, and for the effects of inhibitors, such as secreted frizzled-related proteins (sFRP) and Dickkopf (DKK). This model will hopefully provide a flexible framework for identifying potential targets for intervention in the Wnt signaling pathway, which is often linked to different types of diseases, including cancer. The work was a joint project with Yuri Kogan, Gili Hochman and Zvia Agur.

Work Program for 2011

This year, Karin's research subjects continue to be focused on the Wnt signaling pathway. We will represent several cancer-related mutations in the Wnt signaling model and use the mathematical analysis to look for treatment modality that will be effective for these mutants. The Wnt signaling model will be extended to a molecular mathematical model including the main signaling pathways controlling cell replication and differentiation in order to study normal and cancerous cell behavior. Eventually, the model will be integrated with mathematical descriptions of inter-cellular regulation as well as the overall tissue dynamics in order to develop a multi-scale framework that will be employed to study normal and cancerous tissue behavior. In addition, Karin will be involved in testing the general algorithm for in-treatment guidance of individualized therapy for more indication and treatment.

Publications

Kogan Y., Halevi-Tobias K., Hochman G., Baczmanska A. K., Leyns L., Agur Z. Synergistic effect of sFRP1 and Dkk1 on ß Catenin accumulation: results from a new mathematical model of the Wnt signaling pathway. 2011 In preparation.
Kogan Y., Halevi-Tobias K., Elishmereni M., Vuk Pavlović S., Agur Z. In–Treatment Personalization of Immunotherapy by a New Algorithm Applied to Clinical Data. 2011 In preparation.
Kronik N., Kogan Y., Elishmereni M., Halevi-Tobias K., Vuk Pavlović S., Agur Z. (2010) Predicting Effect of Prostate Cancer Immunotherapy by Personalized Mathematical Models PLoS one 2010 5(12): e15482
Gross-Mesilaty, S., Reinstein, E., Bercovich, B., Tobias, K.E., Schwartz , AL., Kahana, C. & Ciechanover, A. Basel and human papilloma virus E6 oncoprotein-induced degradation of Myc proteins by the ubiquitin pathway. Proc. Natl . Acad. Sci. U S A, 1988 95, 8058-8063.
Tobias K.E., Kahana C. Exposure to ornithine results in excessive accumulation of putrescine and apoptotic cell death in ornithine decarboxylase overproducing mouse myeloma cells. Cell Growth & Differ. 1995 6 1279-1285.
Tobias K.E., Shor J. & Kahana C. c-Myc and Max transregulate the mouse ornithine decarboxylase promoter through interaction with two downstream CACGTG motifs. Oncogene 1995 11, 1721-1727.
Tobias K.E., Mamroud-Kidron E., Kahana, C. Gly387 of murine ornithine decarboxylase is essential for the formation of stable homodimers Eur. J. Biochem. 1993 218, 245-250.
Tobias K.E., Kahana C. Intersubunit location of the active site of mammalian ornithine decarboxylase as determined by hybridization of site-directed mutants. Biochemistry 1993 32, 5842-5847.