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Nir Hacohen, PhD

Associate Professor, Department of Medicine, Harvard Medical School

Immunologist, Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital

Contact Info

Nir Hacohen
Massachusetts General Hospital
149 13th St
Charlestown, MA, 02129
Mailstop: 149-8410
Phone: 617-724-3768
Fax: 617-726-5651
nhacohen@partners.org

Assistant

Not Available.

DF/HCC Program Affiliation

Cancer Immunology

Research Abstract

Sensing by the innate immune system. The immune system can normally distinguish and respond appropriately to a broad diversity of pathogens and antigens that it encounters during a lifetime including the products of bacteria, fungi, viruses and mammalian cells. Dendritic cells (DCs) play an important role in this process through their highly developed machinery to sense and engulf pathogens and to process and present digested peptides to T cells. We have previously shown that dendritic cells exhibit unique gene expression signatures, including specific cytokine, chemokine and costimulator expression, in response to distinct pathogens. We are interested in addressing the following kinds of questions: (1) What are the mechanisms by which each innate sensor induces specific and common signatures of gene expression? (2) What is the role of innate sensory pathways in the induction of protective immunity to infections and tumors? (3) How are these pathways dysregulated under some conditions, leading to inflammatory disorders or autoimmune disease? To address these questions, we utilize genetic, biochemical and cell biological approaches to systematically dissect the genetic circuitry of pathogen-sensing pathways and their role in initiating and guiding immune responses.


RNAi library for loss-of-function genetics in mammalian cells. Genetic screening in lower organisms has been the basis of critical discoveries across many fields. To develop a method for systematic genetic screens in mammals, we have: (a) generated genome-wide lentiviral shRNA libraries targeting human and mouse genes, in collaboration with several laboratories at the Broad Institute (Moffat et al., 2006); (b) developed high-throughput protocols to generate viral particles and infect cells in order to enable large-scale loss-of-function screens in mammalian cells; (c) demonstrated that these viruses can infect primary dendritic cells (and many other immune and non-immune cell types) and silence genes that control DC functions. As the Broad Institute RNAi Consortium and Platform continues to refine this technology and develop applications to many biological systems, we have begun to apply this powerful methodology to dissect the circuitry of the innate immune system.

Publications

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