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BIOGRAPHICAL SKETCH NAME: Paust, Silke eRA COMMONS USER NAME (credential, e.g., agency login): SILKEPAUST POSITION TITLE: Assistant Professor of Immunology EDUCATION / TRAINING DEGREE Completion INSTITUTION AND LOCATION (if applicable) Date MM/YYYY University of Wisconsin-Madison, WI B.S. 05/1997 FIELD OF STUDY Biochemistry Washington University, St. Louis, MO M.S. 01/2000 Harvard Medical School, Boston, MA Ph.D. 06/2005 Biomedical Sciences Immunology Harvard Medical School, Boston, MA Instructor 01/2012 Immunology Baylor College of Medicine, Houston, TX Assistant Professor 09/2013 Immunology A. PERSONAL STATEMENT My post-doctoral work demonstrated that subsets of Natural Killer cells are long-lived adaptive immune cells capable of antigen-specific immunological memory to viruses and altered self (Nature Immunology 2010 & 2011, cited > 400 times). These important findings open the door for the development of novel Natural Killer cell-based vaccines and therapeutics. Thus, the efforts in my laboratory are focused on three specific goals as the cornerstones of my NIH funded research program: (i) the identification of the molecular mechanism(s) of immunological memory in murine and human NK cells (ii) the development of novel vaccination strategies that elicit adaptive immunity in murine and human NK cells for the prevention of viral infection, and (iii) the development and efficacy testing of novel NK cell-based therapeutics to treat malignancy. B. POSITIONS AND HONORS Positions and Employment 2013 - present: Assistant Professor, Center for Human Immunobiology, Department of Pediatrics, Texas Children’s Hospital, Baylor College of Medicine, Houston, TX. 2012 - 2013: Instructor, Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA. 2012: Member of the local organizing committee, AIDS vaccine 2012, Boston, MA. Honors 2004: The Hauser Fellowship, Harvard University, for outstanding achievements in scientific research and teaching throughout their graduate school training. 2007-09: Irvington Postdoctoral Fellowship of the Cancer Research Institute, New York, NY. 2010-12: Postdoctoral Fellowship of the Ragon Institute of MGH, MIT & Harvard, Boston, MA. 2012-13:T32 Transfusion Biology and Cellular Therapies NIH training grant. 2014: Women & Diversity Paper of the Year Award from the Society of Leukocyte Biology & FASEB, for the most highly cited publication in innate immunity of the past five years. C. CONTRIBUTIONS TO SCIENCE 1. My graduate studies and collaborative work I performed as an Instructor at Harvard Medical School, focused on the regulation of T cell mediated inflammatory responses in the context of autoimmune disease, and mechanisms of T cell regulation by cell-intrinsic and extrinsic pathways, including thymic selection, regulatory T cell-mediated suppression and dendritic cell and neuronal regulation of T cell mediated immune responses: I. Plas DR, Williams CB, Kersh GJ, White LS, White JM, Paust S, Ulyanova T, Allen PM, and Thomas ML. The tyrosine phosphatase SHP-1 regulates thymocyte positive selection. Journal of immunology (Baltimore, Md. : 1950). 1999; 162(10):5680-4. PMID:10229799. II. Paust S, Lu L, McCarty N, Cantor H. Engagement of B7 on effector T cells by regulatory T cells prevents autoimmune disease. Proceedings of the National Academy of Sciences of the United States of America (PNAS). 2004; 101(28):10398-403. PMID:15235129. III. McCarty N, Paust S, Ikizawa K, Dan I, Li X, and Cantor H. Signaling by the kinase MINK is essential in the negative selection of autoreactive thymocytes. Nature Immunology. 2005; 6(1):65-72. PMID:15608642. IV. Riol-Blanco L, Ordovas-Montanes J, Perro M, Naval E, Thiriot A, Alvarez D, Paust S, Wood JN, and von Andrian UH. Nociceptive sensory neurons drive interleukin-23-mediated psoriasiform skin inflammation. Nature. 2014; 510(7503):157-61. PMID: 24759321 2. Discovery of antigen-specific anti-viral immunological memory mediated by Natural Killer cells. My post-doctoral work was first to discover a subset of murine NK cells capable of immunological memory responses to viral antigens, such as Influenza A derived Matrix Protein 1 and Human Immunodeficiency Virus encoded group antigen and envelope. This potent anti-viral NK immunological memory is distinct from that described for CMV. It occurs to a multitude of viral antigens that are distinguished by memory NK, which protect the vaccinated host from severe disease. 3. Discovery of the critical role for the chemokine receptor CXCR6 in NK cell-mediated antigen-specific memory. My post-doctoral further work discovered the only memory-associated marker for non-CMV viral antigen-specific murine memory NK cells, called CXCR6. In mice, memory of haptens and viruses depended on CXCR6, a chemokine receptor on hepatic NK cells required for long-term survival and memory function of antigen-primed NK cells, but not for antigen recognition. I. Paust S, Gill HS, Wang BZ, Flynn MP, Moseman EA, Senman B, Szczepanik M, Telenti A, Askenase PW, Compans RW, von Andrian UH. Critical role for the chemokine receptor CXCR6 in NK cell- mediated antigen-specific memory of haptens and viruses. Nature Immunology. 2010 (12): 1127-35. PMID: 20972432; PMCID: PMC2982944 II. Majewska-Szczepanik M*, Paust S*, von Andrian U.H., Askenase P.W. and Szczepanik M. NK cell mediated contact sensitivity develops rapidly and depends on IFN-α, IFN-γ AND IL-12. Immunology 2013 May 10; * equal contribution PMID: 23659714; PMCID: PMC3809710 III. Paust S, Senman B, von Andrian UH. Adaptive immune responses mediated by natural killer cells. Immunological Reviews. 2010 May; 235(1): 286-96. PMID: 20536570; PMCID: PMC2911633 IV. Paust S, von Andrian UH. Natural killer cell memory. Nature Immunology 2011 Jun; 12(6): 500-8. PMID: 21739673 Complete List of Published Work in MyBibliography: http://www.ncbi.nlm.nih.gov/sites/myncbi/silke.paust.1/bibliography/47563634/public/?sort=date&direc tion=ascending 3. Report of Technological Innovations Year Title 2011 MODULATION OF NK CELL ANTIGEN SPECIFIC EFFECTOR ACTIVITY BY MODULATION OF CXCR6 (CD186) International Application No.: PCT/US2010/05856 ONGOING RESEARCH SUPPORT 1R01 AI116282-01A1 - Paust (PI) 02/01/2014 – 01/31/2020 Sponsor: NIH Harnessing NK Memory To Protect Against HIV Infection 3.0 cal. mo. 5R01AI099483-02 PI - Rico-Hesse; Role: Co-I Sponsor: NIH Mosquito Saliva in Dengue Virus Pathogenesis 1.8 cal. mo. 12/12/2012 – 11/3/2017 P30 AI036211-20 CFAR Pilot Award - Paust (PI) 05/01/2015 – 04/31/2016 Sponsor: NIH Curing Chronic HIV Infection With Adoptive Natural Killer Cell Immunotherapy 0.6 cal. mo. DLDCC Award - Paust (PI) 06/15/2015 – 04/31/2016 Sponsor: Dean L Duncan Cancer Center Adoptive Natural Killer Cell Mediated Lung Cancer Immunotherapy 0.6 cal. mo. ASH Bridge Award - Paust (PI) Sponsor: American Society of Hematology Molecular Origin of NK memory 0.6 cal. mo. 06/15/2015 – 04/31/2016 SPORE Developmental Projects - Paust (PI) 06/15/2015 – 04/31/2016 1.2 cal. mo. Sponsor: NCI Targeting Tumor Associated Myeloid Derived Suppressor Cells With Adoptive Natural Killer Cell Immunotherapy For The Treatment Of Lymphoma And Solid Tumors. COMPLETED RESEARCH SUPPORT 30-DK079638 - PI: Paust 07/15/2014 – 07/14/2015 Sponsor: Pilot/Feasibility Program of the Diabetes Research Center at Baylor College of Medicine with National Participation. Harnessing iPSC-derived pancreatic β islets & humanized mice to fight type 1diabetes The goal of this research is to cure type 1 diabetes by β islet transplantation and prevention of graft rejection. 07/01/2014 – 06/30/2015 Pediatrics Pilot Award - PI: Paust Sponsor: Baylor College of Medicine Evaluation of a novel oral HIV vaccine The goal of this project is to evaluate antigen presentation and lymphocyte activation by a novel pollen-based oral HIV vaccine in mice. Alkek Pilot Award - Paust (PI) 09/01/2014 - 08/31/2015 Sponsor: Albert and Margaret Alkek Foundation, Houston, TX Harnessing M2e-Specific Monoclonal Antibodies As Influenza A Therapeutics The objective of this proposal is to develop and characterize novel patentable and clinically relevant influenza A matrix protein 2 extracellular domain-specific monoclonal antibody-based therapeutics for the treatment of Influenza A infection.