Skip Ribbon Commands
Skip to main content
Researchers
  • Prof.  David Naor
Prof David Naor
 
Research Group Activities 
CD44 and RHAMM are migration-supporting molecules in inflammatory and cancer cells. We have showed that targeting cell surface CD44 or RHAMM (receptor hyaluronic acid mediated motility or CD168) molecules, by anti-CD44 or anti-RHAMM monoclonal antibodies (mAbs) or by CD44 gene vaccinations reduce or even eradicate inflammatory and malignant activities in mouse models of rheumatoid arthritis (RA; PNAS 101:18081-18086,2004), multiple sclerosis (J Neurol Sci 258:17-26, 2007), type 1 diabetes (T1D;PNAS 97:285-290, 2000), malignant lymphoma (J Cell Sci 114:3463-3477, 2001) and breast cancer (Mol Cac Ther 7: 1615-1623,2008 , 2008).
 
This approach was effective even when the targeting of the migration- supporting molecules was accomplished after the onset of disease (e.,g., for T1D see Weiss et.al., PNAS, 97:285-290,2000). Exploring the involvement of CD44 in RA pathology, we have discovered a CD44 variant (designated CD44vRA) that is generated by alternative splicing and exclusively expressed on joint inflammatory cells of RA patients (J Clin Invest 111:1211-1220,2003). Monoclonal antibodies (mAbs) directed against CD44vRA (anti-CD44vRA mAbs) kill by apoptosis joint inflammatory cells derived from RA patients, but not peripheral leukocytes derived from the same patients. Using relevant controls, we further showed that anti-CD44vRA mAbs are RA-specific and when injected into mice with collagen-induced arthritis (CIA) they reduce the joint inflammation (J Autoimm. 28,99-113,2007).
 
The clinical feasibility of the anti-CD44vRA mAbs is now under investigations in preclinical models. We further found that when CD44 is genetically deleted, RHAMM can compensate for CD44 in supporting in vitro cell migration as well as in supporting in vivo invasion of inflammatory cells into the joints of mice with CIA (the animal model of RA; PNAS, 101:18081-18086, 2004). In the animal model of T1D, unlike in CIA, CD44-null NOD mice showed stronger resistance to the disease development than corresponding wild type mice, but the invasion of the inflammatory cells into the pancreatic islets was almost equel by both type of cells. These results suggest that RHAMM alone can support the invasion into the pancreatic islets (insulitis), yet, this event is essential, but not sufficient to induce T1D. We predicted that the generation of T1D is dependent on expression of CD44 on the insulin secreting β cells, as cell surface CD44 can deliver, after activation, apoptotic signals, leading to program cell death. Indeed, we have found in in vitro assay that glucose-stimulated pancreatic islet cells derived from wild type NOD mice showed reduced insulin secretion after incubation with a cocktail of pro-inflammatory cytokines.
 
In contrast, the insulin secretion by corresponding cells from CD44-null mice is not influenced by the presence of pro-inflammatory cytokines, suggesting that CD44-null insulin secreting β cells can resist the inflammatory attack by invading cells. In wild type NOD mice RHAMM collaborates, or may even synergizes with CD44 to support invasion into the pancreatic islets. In summary, in NOD wild type mice RHAMM and CD44 cooperate in supporting inflammatory cell invasion into the pancreatic islets (but RHAMM can do the “job” alone if CD44 is missing). Yet, for the developmment of T1D, the insulin secreting β cells must express CD44 in order to be killed by the invading cells.
 
In a different study we have found that peripheral blood leukocytes (PBLs) derived from Graves’ disease patients with eye complications (but not from patients that exclude such complications) generate regulatory T (Treg) cells after their in vitro stimulation with anti-T lymphocyte globulin (ATG; J Clin Endocrinol Metab 96: 422-429,2011). We further found that the ATG-induced Treg cells express, in addition to the standard, well known Treg markers (FoxP3, GITR etc), a novel biomarker - activated CD44 (CD44 that can bind HA). Such Treg cells were detected in vitro after simulation with ATG and in vivo after injection of ATG into patients undergoing stem cell engraftment. At present we continue to explore the role of CD44 and RHAMM in health and disease.
 
 
 
Group Members
 
David Naor, Head of group
 
Nathalie Assayag Asherie, Role of CD44 in type 1 diabetes
 
Talia Weiss, Role of RHAMM in type 1 diabetes
 
Ariel Ginzberg, Role of RHAMM in type 1 and type 2 diabetes. In vivo studies
 
Robert Reiner, Role of CD44 in mesenchymal stem cells, regenerating bone
 
Lora Eshkar Sebban, Role of CD44 in rheumatoid arthritis
 
 
Curriculum Vitae  
Education
 
1960-1963
The Hebrew University, Jerusalem B.Sc. Biology
 
1963-1965
The Hebrew University-Hadassah Medical School, Jerusalem M.Sc. Biochemistry
 
1965-1968
Ph.D. Thesis: "Antigen Uptake of Lymphoid Cells in Normal, Immune, and Tolerant Mice"
 
Experience
 
1965-1968
Instructor, Department of Immunology, Hebrew University-Hadassah Medical School
 
1969
Lecturer, Department of Immunology, Hebrew University-Hadassah Medical School
 
1969-1971
NIH International Post-Doctoral Fellow, University of California, Berkeley
 
1971
Research Associate, University of California School of Medicine, San Franciso
 
1971-1973
Lecturer, Department of Immunology, Hebrew University-Hadassah Medical School
 
1973-1978
Senior Lecturer, Department of Immunology, Hebrew University-Hadassah Medical School
 
1975-1976
Associate Visiting Professor, Department of Microbiology and Immunology, UCLA
 
December 1976
Visiting Professor, School of Public Health, University of Teheran
 
1979-1982
Chairman of Teaching Committee of Micriobiology
 
March 1979, June 1980
Visiting Professor, University of South Florida, Tampa, Florida
 
1978
Associate Professor, Hebrew University-Hadassah Medical School
 
Summer 1984
Visiting Professor, Harvard Medical School
 
Summer 1985
Visiting Scientist, Memorial Sloan-Kettering Cancer Institute, New York
 
October 1985
Full Professor, Hebrew University-Hadassah Medical School
 
May 1987
Milton Winograd Professor of Cancer Studies
 
September 1987, November 1988
Visiting Professor, Charing Cross Sunley Research Centre, London
 
Invited speaker
 
1976
Participant in NIH workshop on tumor membranes, Colorado
 
March 1979
RES meeting at Philadelphia, Pennsylvania
 
April 1979
Keynote address speaker at Meeting of American Cancer Society, Florida Division
 
July 1981
Sapporo Cancer Seminar on Tumor Escape, Mechanism, Sapporo, Japan
 
October 1981
New York Academy of Sciences Conference on Immunological Tolerance of Self and non Self
 
October 1983
Invited speaker and chairperson at the First Joint Conference of The Israel Biological societies
 
September 1988, September 1991, September 1993, September 1994, September 1996, October 1998, September 1999, September 2000, September 2001, September 2002, September 2003, September 2005, September 2007, September 2008, September 2010
Oxford Symposium on "T Cell activation in Health and Disease". Oxford
 
 
October 1990
New York Academy of Sciences conference on "Antigen and clone-specific immunoregulation". New York, (Plenary Session)
 
October 1994
Conference "Oncogenes, tumor antigens and MHC molecules". Jean, Spain
 
May 1995
International Conferenence on tumor microenvironment: progression, therapy & prevention, Tiberias
 
September 2000
International Meeting on Inflammatory Cytokines, Ma’ale Hachamisha, Israel
 
2003
Hyaluronan 2003 symposium. Cleveland, USA
 
October 2003
Diabetes Symposium, Jerusalem
 
March 2006
Israel Immunological Society. Annual meeting
 
March 2006
International Symposium on prevention of type 1 dibetes. The new frontiers. Barcelona
 
International Congress on Autoimmunity.Tel Aviv 1999, Budapest, 2004; Sorrento, 2006, Porto 2008 (plenary sessions), Ljubljana 2010 (plenary session)
 
April 2008
Fourth Annual PEGS. Assessment of Immunogenicity in Clinial Trials. Boston
 
May 2008
Louisiana Cancer Research Consortium. Invited Speakers program. New Orleans
 
International Conference on Human Antibodies and Hybridomas. Dublin, 2004, New York. 2009, Porto 2010
 
2010
BIT’s International Congress of Antibodies, Beijing
 
2010
ILSI-Biomsd, Tel aviv
 
Grants
 
Recipient of Leukemia foundation grant, 1973 ($20,000).
 
Recipient of Leukemia foundation grant, 1977 ($20,000).
 
Recipient of grant from NIH, 1979-1982 ($150,000).
 
Recipient of Schonbrun grant, 1983 ($12,000).
 
Recipient of Cancer Research Institute grant, 1983-1985 ($103,000).
 
Recipient of grant from "Seragen" Inc., Boston, 1984 ($61,000).
 
Recipient of the United States-Israel Binational Science Foundation, 1986-1989 ($100,000).
 
Recipient of Concern Foundation grant, 1990 ($37,500).
 
Recipient of Israel Cancer Research fund grant, 1990-1991 ($40,000).
 
Recipient of grant from Israel Ministry of Health, 1991-1992 ($15,000)
 
Recipient of grant on the effect of insulin on tumor growth from Novo Nordisk, Denmark,1992-1993 ($40,000)
 
Recipient of grant from Israel Cancer Society, 1993-1995 ($19,000)
 
Recipient of grant from German Cancer Foundation, 1995-1997 ($180,000)
 
Recipient of grant from Johnson and Johnson, 1995-1998 ($255,000)
 
Recipient of grant from German-Israel Foundaiton, 1996-1999 (DM353,000)
 
Recipient of grants from Horowitz Foundation, 1999 ($36,000), 2000 ($48,000)
 
Recipient of grant from CapCURE, 2000 ($50,000)
 
Recipient of grant from D-CURE,2004-2005 ($I25,000)
 
Recipient of grant from FRIDA,2004-2005 ($45,0000)
 
Recipient of grant from Israel Science Foundatoin (ISF),2004-2007 ($90,000)
 
Recipient of grant from the Israel Ministery of Commerce and Industry (“Bereshit”,2004-2009 ($277,000)
 
Recipient of grant from Rosetrees, London UK, 2007-2008 (£19,000).
 
Recipient of grant from Teva, Israel, 2007 ($10,000).
 
Recipient of grant from Prochon, Israel, 2007 ( $12,000).
 
Recipient of grant from Fresenius, Munich, Germany. 2007-2009 (€ 63,000)
 
Recipient of grant from Johnsom &Johnson, 2010 ( $ 30,000)
 
Recipient of grant from Yissum (“Baby Seed”),2010 ( $ 50,000) 
 
Recipient of grant from Israel Ministery of Commerce and Industry (”Nofar”¬) 2010-2011 ($110,000)
 
Prostate Cancer grant (with my collaborator Prof Eli Kedar) 2010 ($ 23,000)
 
Recipient of a grant from Johnson & Johnson 2011-2012 ($ 200,000)
 
Honours and Awards
 
Award from Johnson & Johnson, Focused Giving Program "In recognition of outstanding research toward the advances of science and technology in health care." 1994
 
An unexpected error has occurred.
 
website by Bynet Software Systems