Dr. Gili Hochman has completed studies towards a Ph.D. degree in the field of theoretical chemistry, in the department of chemistry at Bar-Ilan University. Her thesis work, under the supervision of Prof. Kenneth G. Kay, included an analytical and numerical research in the area of semiclassical mechanics, using classical mechanics to approximate solutions to problems in quantum mechanics. Gili joined IMBM in January 2010. In IMBM, she takes part in the Cancer Stem Cell project.
Scientific activity in 2011
During this year, Gili’s research has been focused on signaling pathways in cancer stem cells, particularly the Wnt signaling pathway. The Wnt canonical pathway is one of the intracellular pathways responsible for fate decision of stem cells, and aberrant activation of this pathway is common in different types of diseases, including cancer. This year, the mathematical model developed in 2009-2010 (with Yuri Kogan, Karin Halevi-Tobias and Zvia Agur), describing the Wnt signaling pathway, has been expanded, and further adjusted to represent cancer-related mutations in this pathway. The model describes Wnt-induced Lef/Tcf transcriptional activity, followed by ?-Catenin accumulation. Several mutations in Apc, which are known to be common in several cancer indications, have been studied, and the model has been used to simulate the aberration in Wnt pathway activity in mutated cells. As the model includes the pathway regulation by inhibitors, such as Dickkopf (DKK) and secreted frizzled-related proteins (sFRP), it enabled studying the effects of Wnt and its inhibitors on the Wnt pathway activity in the mutated cells. This allowed to suggest effective targets for therapeutic intervention in the Wnt signaling pathway, which would hinder the cancer-deriving effect of the oncogenic mutation, and restore normal functioning of the cells.
Work Program for 2012
This year, Gili's research subjects continue to be focused on signaling pathways in cancer stem cells. The model for the Wnt signaling pathway with cancer-related mutations will be further expanded, to explicitly include the effect of the pathway activity on cell proliferation. It will be used to study the effect of specific oncogenic mutations in the Wnt pathway on cancer progression, especially on the metastatic process. For this purpose, Gili is coordinating the initiation of a joint project of IMBM with Dr. Prahlad T. Ram's research group, in the Department of Systems Biology in UT MD Anderson Cancer Center. Experiments will be designed and conducted to yield systems-biological information, both on intracellular processes proteins and cell-cell interactions, which will be used to validate, expand and train the model to study the effect of specific mutations on cancerous phenotypes. Hopefully, this model will enable better understanding of the effects of critical mutations in the Wnt pathway on the metastatic process, and will be used to look for the most effective possible treatment modalities for these mutants.
In addition, the Wnt pathway model will be extended to include other major pathways involved in cell fate decision, such as Notch and Shh. Therapeutic modulation of these pathways, switching SCs from proliferation to differentiation, may represent a novel treatment approach for cancer. Eventually, the model will be integrated with mathematical descriptions of inter-cellular regulation and microenvironmental interactions, as well as the overall tissue dynamics. This multi-scale framework will be employed to study normal and cancerous tissue behavior, aiming to find how tissue homeostasis is normally controlled, how it is altered in cancer, and how this alteration can be manipulated.
- Hochman G., Kogan Y., Vainstein V., Shukron O., Lankenau A., Boysen B., Lamb R., Berkman T., Clarke R.,Duschl D., Agur Z. Evidence for Power Law Tumor Growth and Implications for Cancer Radiotherapy. in Mathematical modelling of cancer growth and treatment, M Bachar, J Batzel, M Chaplain (eds). in Springer Lecture Notes in Mathematics Biosciences (LNMBIOS) Series, Volume 4, In press.
- Hochman G., Agur Z. Deciphering Fate Decision in Normal and Cancer Stem Cells – Mathematical Models and Their Experimental Verification. in Mathematical Models and Methods in Biomedicine, A. Friedman, E. Kashdan, U. Ledzewicz and H. Sch?ttler (eds). Springer 2012, pp. 203-232.
- Kogan Y, Halevi-Tobias KE, Hochman G, Baczmanska AK, Leyns L, Agur, Z. A new validated mathematical model of the Wnt signaling pathway predicts effective combinational therapy by sFRP and Dkk Biochem J 2012, 443, pp. 115–125 PMID; 22356261.
- Hochman G., Kay K. G. Tunneling in two-dimensional systems using a higher-order Herman–Kluk approximation, J. Chem. Phys. 2009 130,
- Hochman G., Kay K. G. Tunneling by a semiclassical initial value method with higher order corrections, J. Phys. A: Math. Theor. 2008 41(38), 385303
- Hochman G., Kay K. G. Semiclassical Corrections to the Herman-Kluk Propagator, Phys. Rev. A 2006 73, 064102
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