Dr. Moran Elishmereni

Dr. Moran Elishmereni joined IMBM in November 2004, after obtaining a B.Sc. in Computational Biology at Bar-Ilan University. She completed her MSc (2007) and PhD (2012) at the Institute for Drug Research in the Hebrew University of Jerusalem, where she studied immunopharmacology under the supervision of Prof. Francesca Levi-Schaffer. Her thesis centered on the “Allergic Synapse”, defining a role for mast cell/eosinophil interactions in regulating inflammatory responses. In IMBM, Moran takes part in various Cancer Therapy projects.

Scientific activity

    Over the past years, Moran has led a number of IMBM projects in the context of cancer therapy. The field of immunity was focally underscored in her work, which has focused on building mathematical models mainly for the dynamical interactions between the tumor and the immune system. In these complex systems, she examines the influence of various novel therapeutic agents, for the purpose of rationalizing their clinical application and maximizing their benefit. Together with Dr. Antonio Cappuccio and Yuri Kheifetz, she has constructed a PK/PD/disease model of the immunomodulatory cytokine Interleukin (IL)-21, in development for treating solid cancer patients. The model was prospectively validated using preclinical data from NovoNordisk AG, and has yielded important therapeutic insights concerning clinical IL-21 therapy. Moran also collaborated with Yuri Kheifetz in designing a combined pharmacometric/biomathematical model for thrombopoiesis and the effect of IL-11 therapy on this process, with the goal of using this cytokine for alleviating chemotherapy-induced thrombocytopenia in solid cancer patients. Together with Yuri Kogan, Moran devised a mathematical model for the Th1/Th2 imbalance of the immune system in cancerous settings. She also participated in mathematical modeling of immunotherapies for advanced prostate cancer (with Yuri Kogan and Dr. Karin Halevi): In collaboration with Prof. Stanimir Vuk-Pavlovic (Mayo Clinic Rochester, USA), a model for cellular vaccination therapy was devised and validated retrospectively using data from a Phase II trial of an allogeneic whole-cell vaccine in hormone-refractory patients. The team followed up by developing a novel and general approach for model-aided personalization of vaccination therapy in real-time. Moran later developed dynamic models for prostate cancer progression and treatment by hormonal-based drugs, and explored their application in the clinical realm by training and validating these models on actual retrospective patient data. She recently led a pilot study examining the potential of a mathematical/statistical model-based algorithm for predicting individual endpoints of hormone sensitive prostate cancer patients to androgen deprivation therapy, in collaboration with Dr. Manish Kohli at Mayo Clinic Rochester, USA. Moran is continuing to study the application of clinically applicable algorithms for various indications and therapeutic settings.

    Moran’s scientific work has been published in 18 peer reviewed papers in mathematical, medical, biological and interdisciplinary journals over the last decade.

Publications

  1. Elishmereni M, Kheifetz Y, Shukrun I, Bevan GH, Nandy D, McKenzie KM, Kohli M, Agur Z. Predicting time to castration resistance in hormone sensitive prostate cancer by a personalization algorithm based on a mechanistic model integrating patient data. Prostate, 2016 76(1) pp. 48-57.
  2. Kheifetz Y, Elishmereni M, Agur Z. Complex pattern of interleukin-11-induced inflammation revealed by mathematically modeling the dynamics of C-reactive protein. J Pharmacokinet Pharmacodyn, 2014 41(5) pp.479-91.
  3. Ribba B, Holford NH, Magni P, Troconiz I, Gueorguieva I, Girard P, Sarr C, Elishmereni M, Kloft C, Friberg LE. A review of mixed-effects models of tumor growth and effects of anticancer drug treatment used in population analysis. CPT Pharmacometrics Syst Pharmacol., 2014 3:e113.
  4. Agur Z, Elishmereni M, Kheifetz Y. Personalizing oncology treatments by predicting drug efficacy, side-effects, and improved therapy: mathematics, statistics, and their integration. Wiley Interdiscip Rev Syst Biol Med., 2014 6(3) pp.239-53.
  5. Elishmereni M, Fyhrquist N, Singh Gangwar R, Lehtimaki S, Alenius H, Levi-Schaffer F. Complex 2B4 regulation of mast cells and eosinophils in Murine Allergic Inflammation. J Invest Dermatol., 2014 134(12) pp.2928-37.
  6. Elishmereni M, Bachelet I, Ben-Efraim AH, Mankuta D, Levi-Schaffer F. Interacting mast cells and eosinophils acquire an enhanced activation state in vitro. Allergy, 2013 68(2):171-9.
  7. Kogan Y, Halevi-Tobias K, Elishmereni M, Vuk-Pavlovic S, Agur Z. Reconsidering the paradigm of cancer immunotherapy by computationally aided real-time personalization. Cancer Res., 2012 1;72(9) pp.2218-27.
  8. Elishmereni M, Kheifetz Y, Sondergaard H, Overgaard RV, Agur Z. An integrated disease/pharmacokinetic/pharmacodynamic model suggests improved interleukin-21 regimens validated prospectively for mouse solid cancers. PLoS Comput Biol., 2011 7(9):e1002206.
  9. Kronik N, Kogan Y, Elishmereni M, Halevi-Tobias K, Vuk-Pavlovic S, Agur Z. Predicting outcomes of prostate cancer immunotherapy by personalized mathematical models. PLoS One. 2010 5(12):e15482.
  10. Elishmereni M, Alenius HT, Bradding P, Mizrahi S, Shikotra A, Minai-Fleminger Y, Mankuta D, Eliashar R, Zabucchi G, Levi-Schaffer F. Physical interactions between mast cells and eosinophils: a novel mechanism enhancing eosinophil survival in vitro. Allergy. 2011 66(3) pp.376-85.
  11. Elishmereni M, Levi-Schaffer F. CD48: A co-stimulatory receptor of immunity. Int J Biochem Cell Biol. 2011 43(1) pp.25-8.
  12. Minai-Fleminger Y, Elishmereni M, Vita F, Soranzo MR, Mankuta D, Zabucchi G, Levi-Schaffer F. Ultrastructural evidence for human mast cell-eosinophil interactions in vitro. Cell Tissue Res. 2010;341(3):405-15. (Equal contribution with 1st author).
  13. 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 York.
  14. Elishmereni M, Bachelet I, Levi-Schaffer F. DNAM-1: An amplifier of immune responses as a therapeutic target in various disorders. Current Opinion in Investigational Drugs 2008 9(5) pp.491-6.
  15. Cappuccio A, Elishmereni M, Agur Z. Optimization of Interleukin-21 immunotherapeutic strategies. Journal of Theoretical Biology, 2007 248(2) pp.259-66. (Equal contribution with 1st author).
  16. 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.
  17. 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.

Lectures/Conferences

  • Kogan, Halevi-Tobias, Elishmereni, Vuk-Pavlovic, Agur. Reconsidering the paradigm of cancer immunotherapy by computationally aided real-time personalization. Poster presented in the Israel Immunology Society Meeting, February 2012, Bar-Ilan University, Israel.
  • Kogan, Halevi-Tobias, Elishmereni, Vuk-Pavlovic, Agur. A method for in-treatment personalization of cancer immunotherapy. Oral presentation in the seventh ISABS conference in forensic, anthropologic and medical genetics and mayo clinic lectures in translational medicine, June 2011, Bol, Croatia.
  • Elishmereni, Kheifetz, Sondergaard, Overgaard, Agur. A validated mathematical model of systemic IL-21 immunotherapy in solid cancers for the design of beneficial treatment regimens. Oral presentation in the seventh ISABS conference in forensic, anthropologic and medical genetics and mayo clinic lectures in translational medicine, June 2011, Bol, Croatia.
  • Elishmereni, Alenius, Bradding, Mankuta, Eliashar, Levi-Schaffer. The allergic effector unit: Mast cell-eosinophil paracrine and physical interactions regulate cell survival. Poster presented in the 28th Symposium of the Collegium Internationale Allergologicum (CIA), April 2010, Ischia, Italy.
  • Elishmereni, Alenius, Bradding, Mankuta, Eliashar, Levi-Schaffer. The allergic effector unit: mast cell-eosinophil physical interactions regulate cell survival. Poster
  • Kronik N, Kogan Y, Elishmereni M, Halevi-Tobias K, Vuk-Pavlovic S, Agur Z. Validation of a patient-specific mathematical model of prostate cancer immunity for guiding clinical trials of whole-cell vaccination therapy. Poster presented in the Mathematical Methods in Systems Biology Meeting, January 2010, Tel-Aviv, Israel.
  • 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, Sondergaard, 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.


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