Principal Investigator
Goldyne Savad Institute of Gene Therapy
E-mail: rjacob@hadassah.org.il
Phone: 972-2-677-7848
Fax: 972-2-643-0982
Academic Rank
Lecturer, Hebrew University School of Medicine, Jerusalem, Israel
Affiliation
Hadassah-Hebrew University Medical Center, Jerusalem, Israel
Education
1986-1989 B.Sc. Student major subject: Biology, The Faculty of Science, The Hebrew University of Jerusalem.
1989-1991 M.Sc., Institute of Life Sciences, The Hebrew University, Jerusalem, Israel
1991-1996 Ph.D., Institute of Life Sciences, The Hebrew University, Jerusalem, Israel. Thesis: H19 gene and genomic imprinting in trophoblast cells. Under the guidance of Prof. A. Hochberg and Prof. N. de Groot.
Research interests
Autoimmune diseases, placental protein 14, immunomodulator, cytokine
Selected Recent Publications
Ish-Shalom E, Gargir A, Andre S, Borovsky Z, Ochanuna Z, Gabius HJ, Tykocinski ML, Rachmilewitz J. 2006. {alpha}2,6 Sialylation Promotes Binding of Placental Protein 14 via Its Ca2+ -Dependent Lectin Activity: Insights into Differential Effects on CD45RO and CD45RA T Cells. Glycobiology 16(3):173-83.
Beyth S, Borovsky Z, Mevorach D, Liebergall M, Gazit Z, Asian H, Galun E, Rachmilewitz J. 2005. Human mesenchymal stem cells alter antigen-presenting cell maturation and induce T cell unresponsiveness. Blood 105:2214-9.
Mishan-Eisenberg G, Borovsky Z, Weber MC, Gazit R, Tykocinski ML, Rachmilewitz J. 2004. Differential regulation of Th1/Th2 cytokine responses by placental protein 14. J Immunol Nov 1;173(9):5524-30.
Yaniv E, Borovsky Z, Mishan-Eisenberg G, Rachmilewitz J. 2003. Placental protein 14 regulates selective B cell responses. Cell Immunol Apr;222(2):156-63.
J. Rachmilewitz, Z. Borovsky, G.J. Riely, R. Miller and M.L.Tykocinski. 2003. Negative regulation of T cell activation by placental protein 14 is mediated by the tyrosine phosphatase receptor CD45. J Biol Chem 278:14059-14065.
J. Rachmilewitz, A. Lanzavecchia. 2002. A temporal summation model for T cell activation: Signal integration and antigen decoding. Trends Immunol 23:592-595.
Research group
Zipora Tachover, Ph.D. Phone: 677-8886
Eliran Ish Shalom, B.Sc. Phone: 677-8886
Shaul Beyth, M.D., M.Sc. Phone: 677-8886/4530
Zohar Ochanuna, M.Sc. Phone: 677-8886
Chaya Amsalem, M.D., M.Sc. Phone:
Collaborators
Mark L. Tykocinski, Dept. of Pathology and Laboratory Medicine, Univ. of Pennsylvania, Philadelphia, Pa.
Research Summary
Placental protein 14 (PP14) is a glycoprotein of the lipocalin structural superfamily. PP14 is secreted by the endometrial deciduas of early pregnancy, constituting up to 10% of total decidual protein in the first trimester. Significant concentrations of PP14 are also present in the tumors of reproductive organs as well as in the plasma of patients with these tumors, in male seminal fluid and within cells of the megakaryocytic linease, including platelets. Our overall goal is to elucidate the molecular and cellular mechanisms whereby PP14 inhibits T cells, with the underlying presumption that a more in-depth understanding of PP14's functional properties could set the stage for its use as an immunotherapeutic protein.
In our studies, a major advance was made in understanding PP14's biology, with regard to its immunoinhibitory activities. These findings could well explain, at least in part, alterations in the gravid immune status, encompassing among other things the improvement of clinical manifestations in patients with autoimmune diseases (which share in common an association with cell-mediated immunopathology, linked in some studies to deficient Th2 cytokine production) and a skewing of the cytokine profile (from a Th1 to Th2 phenotype). Thus, our studies could potentially help explain the Th1 dapening and Th2 shift, laying the groundwork for our concept of using PP14 as an immunotherapeutic agent to confer the immunological advantages of pregnancy to non-pregnant women and men with autoimmune diseases.