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Remi J. Creusot, PhD

  • Assistant Professor of Medical Sciences (in Medicine)
  • Principal Investigator, Columbia Center for Translational Immunology
  • Principal Investigator, Naomi Berrie Diabetes Center
  • Director, CCTI Animal Barrier Facility
  • Director, Diabetes Research Center Flow Cytometry and Cell Sorting Core
Remi J. Creusot, PhD

Dr. Remi Creusot is an assistant professor in the Department of Medicine and principal investigator at the Columbia Center for Translational Immunology and the Naomi Berrie Diabetes Center. Dr. Creusot obtained his BS degree in Biochemistry and MS degree in Microbiology from the University of Nancy (France), and received his PhD in Immunology from the University of London at University College London (UK). He subsequently trained at Stanford University, where he was consecutively postdoctoral fellow, research associate and instructor in the Department of Medicine, Division of Immunology and Rheumatology. Dr. Creusot joined Columbia University in November 2012 and his research interests revolve around the pathogenesis and prevention of Type 1 Diabetes. He and his group study how several processes that contribute to the maintenance of immune tolerance are impaired, allowing the progression of the disease. The lab works on several new therapeutic strategies aimed at restoring immune tolerance and blocking autoimmunity. This research allies basic research, preclinical studies using mouse models and translational studies using patient samples.

After joining Columbia University, Dr. Creusot expanded his interests to translational research using human samples and humanized mice to investigate aspects of immune tolerance (or lack thereof) in T1D. The ultimate goal of his research is to firmly reestablish immune tolerance in individuals with T1D, meaning that immune cells would be re-educated to stop attacking insulin-producing beta-cells, or any islet transplant if applicable.

Research Interests

Epitope-based immunotherapy of T1D:

We evaluate several platforms to deliver customized epitopes in an effort to rebuild immune tolerance to beta-cell antigens. Our platforms include:

1) Tolerogenic DNA vaccines;

2) Formulated RNA-based delivery of epitopes and immunomodulators;

3) Soluble antigen arrays (in partnership with Orion Bioscience and University of Kansas).

Tolerogenic antigen-presenting cells in T1D:

We characterize antigen-presenting cell populations in relevant tissues such as pancreas-draining lymph nodes from T1D-prone mice and T1D patients to identify possible functional defects and targets for immunotherapy. These populations include poorly studied lymph node stromal cells which the lab intends to leverage in its efforts to reestablish tolerance.

Development of human diabetogenic T cells:

The lab is using state-of-the-art humanized mouse models to study the development of human T cells that recognize beta-cell antigens in an effort to understand why they are not properly purged or regulated in order to prevent autoreactivity against beta-cells.

The role of Deaf1 in peripheral tolerance and T1D disease development:

We study the biological function of the transcription factor Deaf1 as it relates to immune tolerance in order to better understand the consequences of its loss of function in cells from pancreatic lymph nodes in association with T1D in both the mouse model and patients.

Departments and Divisions

  • Department of Medicine

Languages Spoken

  • French

Education & Training

  • BS, Biochemistry, University of Nancy (France)
  • MS, Microbiology, University of Nancy (France)
  • PhD, Immunology, University College London
  • Fellowship: Stanford University

Lab Locations

  • William Black Medical Research Building

    Phone:
    (212) 305-4735
    Lab Phone:
    (212) 305-4735
    Email:
    rjc2150@columbia.edu

Past Positions

  • 06/2012-10/2012: Instructor of Medicine (Stanford University, Department of Medicine, Division of Immunology and Rheumatology).
  • 08/2007-05/2012: Research Associate (same affiliation as above).
  • 01/2003-07/2007: Post-doctoral Fellow (same affiliation as above).
  • 03/1999-03/2001: Research Assistant (University College London, Department of Immunology).

Patents

Transient expression of immunomodulatory polypeptides for the prevention and treatment of autoimmune disease, allergy and transplant rejection. C Nicolette / CG Fathman / R Creusot [US patent 8513208 issued 08/20/13, EU patent 09713841.6 issued 06/29/15]

Constructs for the optimal presentation of selected epitopes and uses thereof. R Creusot [Patent pending, PCT/US15/55042, filed 10/10/15]

Teaching Responsibilities

  • G4020 Graduate Immunology "Autoimmunity" (Spring 2014-2018)
  • G6055 Advanced Topics in Microbiology & Immunology "Novel concepts in the regulation of immune tolerance" (Fall 2014-2016,2018)
  • G6004 Graduate Pathology "Immune mechanisms in the destruction of beta cells" (Spring 2015-2018)
  • M5108 The Body in Health and Disease, Immunology (Preceptor, Winter 2016-2018)

Committees / Societies / Memberships

2009-present: Immunology of Diabetes Society

2015-present: Federation of Clinical Immunology Societies

2016-present: American Society of Gene and Cell Therapy

Honors & Awards

  • JDRF Transition Award (2013)
  • JDRF Early Career Investigator Travel Award (2010)
  • JDRF Advanced Postdoctoral Fellowship (up to 3 years funding) (2010)
  • JDRF Trainee/Young Investigator Travel Award (2009)
  • JDRF Travel Award (2008)
  • JDRF Travel Award (2007)
  • FOCIS Poster of Distinction Award (2006)
  • JDRF Postdoctoral Fellowship (2 years funding) (2005)
  • Glaxo SmithKline Scholarship (1 year funding, 2001-2002)
  • Leonardo da Vinci Award (EU program for mobility in research, 6 months funding) (1998)

Research Interests

  • Immune tolerance
  • Autoimmunity
  • Type 1 diabetes
  • Dendritic cells
  • Stromal cells
  • Humanized mice

Grants

NIH/NIAID, 1R21 AI110812-01A1; Role: PI (20% effort); Funding period: 08/01/15-07/30/18 ($275,000 direct costs, no-cost extension); Title: Engineering and targeting novel antigen-specific tolerogenic interfaces.

JDRF Research Grant 2-SRA-2017-312-S-B; Role: Subcontract PI (5-20% effort); Funding period: 12/01/16 – 11/30/18 ($227,273 direct costs); Title: SAgAs for T1D re-tolerization.

NIH Grants

  • COLUMBIA DIABETES RESEARCH CENTER (Federal Gov)

    Jul 6 2018 - Jan 31 2023

    NOVEL DNA-BASED PLATFORMS TO RE-ESTABLISH TOLERANCE IN TYPE 1 DIAPETES (Private)

    Jan 1 2018 - Dec 31 2020

    ENGINEERING AND TARGETING NOVEL ANTIGEN-SPECIFIC TOLEROGENIC INTERFACES (Federal Gov)

    Aug 1 2015 - Jul 31 2018

    SAGAS FOR T1D RE-TOLERIZATION (Private)

    May 17 2017 - May 16 2018

    TOLERANCE-INDUCING PROPERTIES OF HUMAN DENDRITIC CELL SUBSETS IN VIVO (Federal Gov)

    Feb 1 2015 - Jan 31 2018

    THE GEORGE S. EISENBARTH NPOD AWARD FOR TEAM SCIENCE NPOD AUTOIMMUNITY GROUP ( (Private)

    Sep 1 2016 - Oct 31 2017

    ROLE OF DEAF1 IN THE PATHOGENESIS OF TYPE 1 DIABETES (Private)

    Jun 1 2013 - May 31 2014

Lab Members

  • Nato Teteloshvili, Postdoctoral Research Scientist
  • Rebuma F. Fite, DVM, PhD, Postdoctoral Research Scientist
  • Jorge Postigo, Postdoctoral Research Scientist

Collaborators

Columbia University collaborators:

Yong-Guang Yang, Donna Farber, Megan Sykes, Arnold Han, Li Qiang, Lance Kam

Outside collaborators:

Cory Berkland (University of Kansas); Mark Anderson (UCSF)

Publications

Creusot RJ, Postigo-Fernandez J, Teteloshvili N. Altered function of antigen-presenting cells in Type 1 diabetes: a challenge for antigen-specific immunotherapy? Diabetes 2018; 67(8):1481-1494.

Kraakman MJ, Liu Q, Postigo-Fernandez J, Ji R, Kon N, Larrea D, Namwanje M, Fan L, Chan M, Area-Gomez E, Fu W, Creusot RJ, Qiang L. Targeted PPARg Deacetylation Dissociates thiazolidinedione’s metabolic benefits from its adverse effects. J. Clin. Invest. 2018 (Epub 05/14/2018).

Dastagir SR, Postigo-Fernandez J, Xu C, Stoeckle JH, Firdessa-Fite R, Creusot RJ. Efficient presentation of multiple endogenous epitopes to both CD4+ and CD8+ diabetogenic T cells for tolerance. Mol. Ther. Methods Clin. Dev. 2016; 4: 27-38.

Creusot RJ, Battaglia M, Roncarolo MG, Fathman CG. Cell-based therapies and other non-traditional approaches for Type 1 diabetes. Stem Cells 2016; 34(4):809-819 (Epub 02/03/2016).

Johannesson B, Sui L, Freytes D, Creusot RJ, Egli D (2015) Towards beta cell replacement for diabetes. EMBO J. 34(7):841-855.

Yip L, Fuhlbrigge R, Taylor C, Creusot RJ, Matsumura T, Whiting C, Schartner JM, Akter R, Von Herrath M, Fathman CG (2015) Inflammation and hyperglycemia mediate Deaf1 splicing in the pancreatic lymph nodes via distinct pathways during Type 1 diabetes. Diabetes. 64(2): 604-617.

Creusot RJ, Giannoukakis, N, Trucco M, Clare-Salzler MJ, Fathman CG (2014) It’s time to bring dendritic cell therapy to Type 1 Diabetes. Diabetes 63(1): 20-30.

Yip L, Creusot RJ, Pager CT, Sarnow P, Fathman CG (2013) Reduced DEAF1 function during Type 1 diabetes inhibits translation in lymph node stromal cells by suppressing Eif4g3. J. Mol. Cell. Biol. 5(2): 99-110.

Junttila IS*, Creusot RJ*, Moraga I*, Bates DL*, Wong MT, Alonso MN, Suhoski MM, Lupardus P, Meier-Schellersheim M, Engleman EG, Utz PJ, Fathman CG, Paul WE, Garcia KC (2012) Redirecting cell-type specific cytokine responses with engineered interleukin-4 superkines. Nature Chem. Biol. 8(12): 990-998. (*Contributed equally)

Creusot RJ, Chang P, Healey DG, Tcherepanova IY, Nicolette CA, Fathman CG (2010). A short pulse of IL-4 delivered by DCs electroporated with modified mRNA can both prevent and treat autoimmune diabetes in NOD mice. Mol. Ther. 18(12): 2112-2120.

Yip L, Su L, Sheng D, Chang P, Atkinson M, Czesak M, Albert PR, Collier A, Turley SJ, Fathman CG, Creusot RJ (2009) Deaf1 isoforms control peripheral tissue antigen expression in the pancreatic lymph nodes during type 1 diabetes. Nature Immunol. 10(9): 1026-1033.

Creusot RJ, Yaghoubi SS, Chang P, Chia J, Contag CH, Gambhir SS, Fathman CG (2009) Lymphoid tissue specific homing of bone marrow-derived dendritic cells. Blood. 113(26):6638-6647.

Kodama K, Butte AJ, Creusot RJ, Su L, Sheng D, Dang D, Hartnett M, Iwai H, Holness C, Soares LR, Fathman CG (2008) Time-dependent and tissue-specific changes in gene expression during disease induction and progression in NOD mice. Clin. Immunol. 129(2):195-201.

Creusot RJ, Mitchison NA (2004) How dendritic cells control cross-regulation between lymphocytes. Trends Immunol. 26(3): 126-131.

Creusot RJ, Thomsen LL, Tite JP, Chain BM (2003) Local cooperation dominates over competition between CD4+ T cells of different antigen/MHC specificity. J. Immunol. 171(1): 240-246.

Creusot RJ, Biswas JS, Thomsen LL, Tite JP, Mitchison NA, Chain BM (2003) Instruction of naïve CD4+ T cells by polarized CD4+ T cells within dendritic cell clusters. Eur. J. Immunol. 33(6): 1686-1696.

For a complete list of publications, please visit PubMed.gov