Julie Magarian Blander
Immunology Institute, Department of Medicine
Icahn School of Medicine at Mount Sinai
1425 Madison Avenue, 12-20D
New York, NY 10029
2007 Searle Scholar
Immune responses begin with innate immune recognition, an evolutionarily conserved form of pattern recognition capable of fine discrimination between the molecular patterns of microorganisms and those present on cells and tissues of the host organism. In higher metazoans, a specific and highly specialized adaptive immune response has evolved, which allows for long-term protection. Mobilization of this adaptive immune response is under direct control of the innate immune system. Our group studies the basic innate immune mechanisms that segregate self from non-self recognition, and control the activation and subsequent course of the adaptive immune response.
We have several areas of research within the laboratory:
Innate immune recognition of microbial infection
Vaccination relies on presenting the innate immune system with molecular patterns characteristic of a given microbial pathogen, with the specific purpose of inducing future protective immunity against that pathogen. Although several good vaccines exist that protect humanity against historically significant microbial pathogens, many of these vaccines were empirically derived without precise knowledge of the molecular mechanisms that make them so successful. Thus, in the face of new microbial threats, such as the most recent outbreaks of H5N1 Influenza A viruses in avian and human populations, we are reminded of the real challenges we face in designing optimal protective vaccines. Importantly, certain poorly characterized aspects of natural infection (not incorporated in most vaccines) are particularly effective in inducing the right combination of signals for generating immune memory. We are interested in discovering innate immune signaling modules that sense new and universal pathogen associated molecular patterns specifically within the context of natural infections. We have devised an experimental system to define and delineate the nature of these signals and the pattern recognition pathways they trigger.
Innate immune control of phagocytosis and antigen presentation
Phagocytosis, an ancient cellular process used to capture food by primitive eukaryotes, later became adapted in higher metazoans to specialized functions in development, tissue remodeling, and host defense. Our research has shown that phagocytosis and one of its consequences, antigen presentation by major histocompatibility complex (MHC) molecules, are controlled by signals from Toll-like receptors (TLRs), a family of signaling pattern recognition receptors that recognize conserved structures shared by large groups of microorganisms. We showed that sub-cellular compartmentalization enables MHC presentation of microbial antigens, but not self antigens, within the context of TLR induced T lymphocyte co-stimulatory molecules. The result is successful activation of T lymphocytes bearing receptor specificities directed against microbial antigens and not self antigens. Our current work aims to identify which TLR signals control antigen presentation, and how these signals regulate the antigen presentation machinery for both MHC class II and MHC class I molecules.
Communicating pattern recognition to the adaptive immune system
Besides their lack of an adaptive immune response, the immune system of plants and invertebrates lacks the organization and structure of lymphoid tissues present within vertebrate animals. The simple architecture characteristic of the Drosophila immune system for example, is replaced by a complex network of mobile cells and vessels that effectively communicate information from peripheral sites where microbial pathogens enter, to lymphoid tissues where adaptive immune responses are initiated. We are studying the basic mechanisms that couple innate immune pattern recognition by mobile cells to the induction of their migration towards lymphoid organs where they perform important functions in antigen presentation and T lymphocyte activation. We are interested in identification of the molecules that link pattern recognition signaling pathways to those triggering migration and the initiation of a discrete program of differentiation in migratory antigen presenting cells.
Recipient of The Society of Leukocyte Biology G. Jeanette Thorbecke Award
Recipent of Irma T. Hirschl and Monique Weill-Caulier Scholar Award
Recipient of the Burroughs Wellcome Investigators in the Pathogenesis of Infectious Disease Award
Recipient of the Harold and Golden Lamport Research Award
|SITE MAP CONTACT US||© COPYRIGHT 2017 KINSHIP FOUNDATION. ALL RIGHTS RESERVED.|