Ph.D.: Weizmann Institute of Science, Israel
Post-doctorate: Duke University & National Institutes of Health, USA
Position: Associate Professor
The Shraga Segal Department of Microbiology, Immunology and Genetics
Faculty of Health Sciences
The successful eradication of an invading pathogen is dependent upon the coordinated actions of the innate and adaptive immune systems. Belonging to the former, natural killer (NK) cells are able to quickly destroy a wide range of hazardous pathogens such as viruses, tumors, bacteria and parasites. In recent years, it has become evident that NK cells rely on a set of activating receptors, including NKp44, NKp30, and NKp46, (collectively known as natural cytotoxicity receptors, NCRs) and NKG2D to kill their targets.
1. Characterization of innate immunity responses to tumors and viral infections – The ultimate goal of our research is to understand how NK cells kill their targets and to identify relevant pathogen-induced ligands that interact with NCRs. Accordingly, we are: a) investigating the in vivo function of NCRs using NKp46 knockout mice challenged with various pathogens and determine mortality, NK distribution, activation and trafficking; b) studying the mechanism by which hemagglutinin (HA), an identified NCR ligand, is recognized by NKp46 and NKp44, and whether the same mechanism applies to other viral proteins; c) using the data collected in above to identify novel NCR pathogens and pathogen-induced ligands. The results of these studies will serve to develop novel therapeutic approaches based on NCR recognition of viruses and tumors.
2. Characterization of the peptidome and glyco-peptidome in the blood of tumor-bearing hosts – Work in our group seeks to identify peptide- and glycan-based cancerassociated blood markers (i.e. the blood peptidome and glyco-peptidome) in the normal and cancer state, to serve as the basis for diagnostic kits designed for the early detection and monitoring of cancer. At a later stage, these results could lead to the development of peptide or glycan-based immunomodulators, inhibitors and other cancer drugs.
Mandelboim O., Lieberman N., Lev M., Paul L., Arnon T., Bushkin Y., Davis D.M., Strominger J.L., Yewdell J.W. and Porgador A. (2001). Recognition of hemagglutinins on virus-infected cells by NKp46 activates lysis by human NK cells. Nature 409:1055-1060.
Hershkovitz O., Rosental B., Rosenberg L.A., Navarro-Sanchez M.E., Jivov S., Zilka A., Gershoni-Yahalom O., Brient-Litzler E., Bedouelle H., Ho J.W., Campbell K.S., Rager-Zisman B., Despres P. and Porgador A. (2009). NKp44 receptor mediates interaction of West Nile and dengue envelope E glycoproteins with Natural Killer cells. J. Immunol. 183(4):2610-2621.
**Gur C., Porgador A., Elboim M., Gazit R., Mizrahi S., Stern-Ginossar N., Achdout H., Ghadially H., Dor Y., Nir T., Doviner V., Hershkovitz O., Mendelson M., Naparstek Y. and Mandelboim O. (2010). The activating receptor NKp46 is essential for the development of type 1 diabetes. Nature Immunol. 11(2):121-128. **AP and OM are equal contributors and co-corresponding authors.
Rosental B., Brusilovsky M., Hadad U., Oz D., Appel M.Y., Afergan F., Yossef R., Rosenberg L.A., Aharoni A., Cerwenka A., Campbell K.S., Braiman A., and Porgador A. (2011). Proliferating Cell Nuclear Antigen is a novel inhibitory ligand for the natural cytotoxicity receptor NKp44. J. Immunol. 187(11):5693-5702.
Jaron-Mendelson M., Yossef R., Appel M.Y., Zilka A., Hadad U., Afergan F., Rosental B., Engel S., Nedvetzki S., Braiman A. and Porgador A. (2012). Dimerization of NKp46 Receptor Is Essential for NKp46-Mediated Lysis: Characterization of the Dimerization Site by Epitope Mapping. J. Immunol. 188(12):6165-6174.
Brusilovsky M., Cordoba M., Rosental B., Hershkovitz O., Andrake M.D., Pecherskaya A., Einarson M.B., Zhou Y., Braiman A., Campbell K.S. and Porgador A. (2013). Genome-Wide siRNA Screen Reveals a New Cellular Partner of NK Cell Receptor KIR2DL4: Heparan Sulfate Directly Modulates KIR2DL4-Mediated Responses. J. Immunol. 191(10):5256-5267.