Immunology Faculty Member - Stephen Elledge, PhD

Stephen Elledge, PhD

Harvard Medical School
Department of Genetics, NRB, Rm.158D
77 Avenue Louis Pasteur
Boston, MA 02115
Tel: 617-525-4510
Fax: 617-525-4500
Email: selledge@genetics.med.harvard.edu



Research description

Understanding how immune cells act to protect us, and, in some cases, induce disease-like states is a central goal of biological research. To achieve this goal we need to understand and interpret the language of the immune system to learn what it is the immune cells are seeing that determine their specificities, the immune epitopes.
I am a geneticist and my lab has been developing genome-wide epitope detection methodologies in order to probe the immune system. We have developed two platforms for the identification of antibody epitopes,
PhIP-Seq/VirScan and PLATO that allow us to profile autoantibodies and viral pathogen antibodies in a proteome-wide manner using just a drop of blood. We have applied these methods to understand viral pathogenesis and autoimmune diseases uncovering key targets of particular autoimmune diseases. For example, we recently discovered that Measles Virus infections, but not vaccines, destroy pre-existing antibody repertoires because we can simultaneously assay all previous pathogen-specific antibodies before and after infections. We have also investigated the detection of T cell epitopes and developed tools such as T-Scan to probe the specificities of T cells in genome-wide screens for both Class I and II MHC presented epitopes. Using these technologies, we are examining the structure of the human immune system in exquisite detail, examining the relationship between diversity and human health and uncovering the targets of autoimmunity.
Other areas of interest involve understanding how viruses evade the immune system. We are performing large-scale genetic screens to understand this for viral genes. We also found the interferon-inducible human restriction factor
IFITM3 broadly prevents viral infection. We are similarly interested in how tumors evade the immune system and what genes allow this to occur. Understanding these mechanisms would allow us to reverse the interference and allow the immune system to gain access to the tumor. Finally, we have been exploring how senescence prevents tumorigenesis. We have found that the senescence-associated secretory phenotype (SASP) suppresses tumorigenesis by recruiting immune cells to the tumor. Overall, we are taking a systems approach to understanding immunology.



Last Update: 8/19/2019



Publications

Kula, T., et al.   (2019) T-Scan: a genome-wide method for the systematic discovery of T cell epitopes.  Cell 78:1016-1028.
Davoli et al. (2017) Tumor aneuploidy correlates with markers of immune evasion and with reduced response to immunotherapy. Science. 2017 Jan 20;355(6322). pii: eaaf8399. doi: 10.1126/science.aaf8399.
Xu, G.J., Kula, T. et al. (2015) Comprehensive serological profiling of human populations using a synthetic human virome. Science, 2015, 348(6239):aaa0698. doi:10.1126/science.aaa0698
Kang, C., et al. (2015) DNA damage response induces inflammation and senescence by inhibiting autophagy of GATA4. Science.  349(6255):aaa5612. doi: 10.1126/science.aaa5612.
Brass, A.L et al. (2009) The IFITM Proteins Mediate Cellular Resistance to Influenza A H1N1 Virus, West Nile Virus and Dengue Virus. Cell 139:1243-1254.
Larman, H.B. et al. (2011) Autoantigen discovery with a synthetic human peptidome. Nature Biotechnology. 29:535-41.
Larman, H.B. et al. (2013) Autoimmunity to Cytosolic 5’-Nucleotidase 1A in Sporadic Inclusion Body Myositis. Annals of Neurology  73(3):408-18.
Xu, GJ, et al. (2016) Systematic autoantigen analysis identifies a distinct subtype of scleroderma with coincident cancer. PNAS 2016 Nov 22;113(47):E7526-E7534



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