Moran Elishmereni

Moran joined IMBM in November 2004, after completing a B.Sc. in Computational Biology at Bar-Ilan University. At IMBM, Moran takes part in the Cancer Immunotherapy project. She is also a third-year direct Ph.D. student in the Faculty of Medicine at the Hebrew University of Jerusalem, under the supervision of Prof. Francesca Levi-Schaffer.

Scientific activity in 2008-2009

    Over the past years, Moran has contributed to a number of projects in the context of cancer therapy, particularly immunotherapy (a novel cancer treatment modality designed to stimulate host immune responses against malignant cells). Her work has focused on designing mathematical models representing tumor-immune system interactions, with the aim of aiding the rational development of drugs and drug regimens that will effectively boost anticancer immunity. Together with Dr. Antonio Cappuccio and Yuri Kheifetz, she has constructed a model of the immune-stimulating protein Interleukin (IL)-21, a drug that is being developed for treatment in melanoma and renal carcinoma patients. The work, published in Cancer Research in 2006, served as a basis for the design of a PK/PD model of IL-21 immuno-modulatory effects. The model was prospectively validated using preclinical data from NovoNordisk AG and has yielded important therapeutic insights concerning IL-21 therapy.

    In addition, Moran has been involved in mathematical modeling of interleukin-11 (IL-11), a cytokine aimed at alleviating thrombocytopenia in chemotherapeutically treated cancer patients. Using a multi-scale ODE modeling approach developed together with Yuri Kheifetz, IL-11 PK/PD was reliably modeled and simulated, resulting in interesting therapeutic predictions.

    Moran has also participated in mathematical modeling of immunotherapeutic vaccination in prostate cancer. In a project carried out with Dr. Natalie Kalev-Kronik, Yuri Kogan and Dr. Karin Halevi, and in collaboration with Prof. Stanimir Vuk-Pavlovic (Mayo Clinic, USA) and Dr. Anthony Walker (OnyVax Ltd.), data of whole-cell vaccination in prostate cancer patients was retrieved by the model, validating it at the clinical level. A novel approach of in-trial model calibration and model-aided guidance of treatment design was shown as a promising avenue.

Work program for 2010


    Moran has been involved in efforts to establish a multiscale project including several European experimentalists, computer scientists, and systems biology experts. The project aims at building a multiscale model of tumor-immune system interactions by combining systems biology approaches with dynamic mathematical modeling, and subsequent preclinical validation in the lab. Such a model will hopefully serve as a strong platform for immunotherapeutic design in cancer. This year, we will continue our collaboration with EU groups in efforts to extend the existing immunotherapy models (IL-21, etc.), as well as to develop and validate new models of cytokine and monoclonal Ab immunotherapy.

Presentations in conferences and meetings

  • Elishmereni, Minai, Ben Efraim, Bachelet, Mankuta, Eliashar, Bradding, Alenius, Levi-Schaffer. Mast cells physically interact with eosinophils in vitro and in the allergic tissue. Poster presented in the Mast Cell Network Meeting, October 2008, Jerusalem Israel.
  • Elishmereni, Kheifetz, Agur. A new strategy for improving interleukin-11 therapy for thrombocytopenia based on a mathematical pharmacokinetic/pharmacodynamic analysis. Oral presentation in European Conference on Mathematical and Theoretical Biology (ECMTB) June 2008, Edinburgh Scotland.
  • Elishmereni, Ben Efraim, Bachelet, Levi-Schaffer. Mast cell-eosinophil cross-talk regulates function and viability of both cells in vitro. Poster presented in American Academy of Allergy, Asthma and Immunology (AAAAI) Annual Meeting, March 2008, Philadelphia USA.
  • Elishmereni, Kheifetz, Inbar, S?ndergaard, Thygesen, Overgaard, Agur. IL-21 immunotherapy in solid cancers: therapeutic insights from a preclinically validated mathematical pharmacokinetic and pharmacodynamic model. Poster presented in AACR International Conference: Advances in Cancer Research- From the Laboratory to the Clinic, March 2008, Dead Sea, Jordan.
  • Elishmereni, Bachelet, Levi-Schaffer. The allergic synapse: A novel regulatory interface between mast cells and eosinophils. Oral presentation in 8th World Congress on Inflammation, June 2007, Copenhagen Denmark.
  • Elishmereni, Cappuccio, Agur. Cancer immunotherapy by Interleukin-21: theoretical evaluation of potential treatment strategies. Poster presented in 18th EORTC-NCI-AACR symposium: Molecular Targets and Cancer Therapeutics. November 2006, Prague, Czech Republic.
  • Elishmereni, Kheifetz, Horowitz, Agur. Modeling the fluid retention side effects of Interleukin-11 administered for treating thrombocytopenia and other diseases. Oral presentation in 5th European Conference of Mathematical and Theoretical Biology (ECMTB), July 2005, Dresden Germany.

Fellowships and workshops


  1. EMBO short-term fellowship. FIOH, Helsinki, Finland, Aug. 2009.
  2. MCRTN Workshop: "New Prospects for Cancer Immunotherapy: Integrating Biomarkers in Mathematical Models" May 2008, Kibbutz Dalia, Israel.
  3. MCRTN Summer school: "Modeling, Mathematical Methods and Computer Simulations of Tumor Growth and Therapy", July 2006, Kolymbari Crete.

Publications

  1. Cappuccio A, Elishmereni M, Agur Z. (2006). Cancer immunotherapy by Interleukin-21: Potential treatment strategies evaluated in a mathematical model. Cancer Research, 66(14):7293-300.
  2. Kheifetz Y, Elishmereni M, Horowitz S, Agur Z. (2006). Fluid-retention side-effects of the chemotherapy-supportive treatment Interleukin-11: Mathematical modelling of putative underlying mechanisms. Computational and Mathematical Methods in Medicine, 7(2-3):71-84.
  3. Cappuccio A, Elishmereni M, Agur Z. (2007). Optimization of Interleukin-21 immunotherapeutic strategies. Journal of Theoretical Biology; 248 (2): 259-66. (Equal contribution with 1st author).
  4. Elishmereni M, Levi-Schaffer F. Skin disorders of inflammation and immune suppression in young and elder: A special role for mast cells. Handbook of skin aging: Market prospective, pharmacology, formulation and evaluation, Dayan Nava Ed., William Andrew Publishing, New YorkAgur, Z., Elishmereni, M., Kogan, Y., Kheifetz, Y., Ziv, I., Shoham, M. & Vainstein, V. (2008). Mathematical modeling as a new approach for improving the efficacy/toxicity profile of drugs: the thrombocytopenia case study. In Preclinical development handbook. Ed. Gad, S.1229–1266. New York: John Wiley and Sons.
  5. Elishmereni M, Bachelet I, Levi-Schaffer F. (2008). DNAM-1: An amplifier of immune responses as a therapeutic target in various disorders. Current Opinion in Investigational Drugs 9(5):491-6.
  6. Minai-Fleminger Y, Elishmereni M, Vita F, Soranzo MR, Mankuta D, Zabucchi G, Levi-Schaffer F. (2009). The human mast cell-eosinophil allergic effector unit: an ultra-structural study, submitted. (Equal contribution with 1st author).

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