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
- Associate Director, Diabetes Research Center Flow Cytometry Core
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.
Immune tolerance and autoimmunity: a brief introduction
Immune tolerance is a process by which the body eliminates or suppresses T cells that may react against self or innocuous environmental antigens. Defects in immune tolerance can lead to autoimmune or allergic disorders. In the case of Type 1 diabetes (T1D) for example, T cells reactive to pancreatic beta-cell antigens are not properly eliminated and/or controlled. The role of eliminating or educating self-reactive T cells is normally fulfilled by specialized “tolerogenic” cells that interact with immune cells, primarily within the thymus, the lymph nodes and the spleen. These cells are referred to as tolerogenic because of two important properties: (1) the ability to present self-antigens (either expressed endogenously or acquired from their surrounding environment) and, as a consequence, to form antigen-specific contacts with self-reactive T cells, and (2) the ability to deliver tolerogenic signals that will cause the deletion or inhibition of those self-reactive T cells, or the induction of suppressive – rather than destructive – functions within those self-reactive T cells. During their development in the thymus, self-reactive T cells have an opportunity to recognize their self-antigens on tolerogenic cells and be adequately dealt with before they can be released into the circulation. Thus, many potentially self-reactive T cells, while in the thymus, can be eliminated or converted into regulatory T cells, which block other self-reactive T cells and protect our tissues from autoimmunity. This process is not perfect, even in healthy individual: some self-reactive T cells escape this selection process and get a step closer to reacting against self-tissues. Fortunately, there are additional tolerogenic cells that T cells can later encounter while circulating in the body, and which constitute one of the focuses of the lab.
Tolerogenic antigen-presenting cells comprise two types of cells: 1) Dendritic cells: they can exogenously acquire self-antigens in tissues and transport them to lymphoid tissues for presentation. They exist under two functional modes: tolerogenic or immunogenic. While their immunogenic mode is useful to fight infections and tumors, it is their tolerogenic mode that we aim to understand and exploit. 2) Stromal cells: these are non-professional antigen-presenting cells that are incapable of mounting immune responses, but have the ability to suppress some autoimmune responses.
Particular stromal cells in the thymus have the ability to express tissue-specific antigens, which is conferred by the function of the protein AIRE. The importance of this process is demonstrated by the observation that AIRE-deficiency in both humans and mice leads to a severe autoimmune syndrome targeting multiple tissues (T1D is observed in ~20% of cases). We have recently discovered that endogenous expression of tissue-specific antigens can also be regulated by DEAF1, a regulator of gene expression that has homologies with AIRE. In both T1D patients and NOD mouse model of T1D, the progression of disease is associated with a defective function of DEAF1 due the alternative mRNA splicing in the pancreatic lymph nodes. In the case of T1D, pancreatic lymph nodes are central, both a major site of disease initiation and a site of competition between tolerogenic and immunogenic cells that present beta-cell antigens. Thus inability of tolerogenic cells to express tissue-specific antigens in this tissue may tip the balance in favor of immunogenic cells eliciting diabetogenic responses.
Departments and Divisions
- Department of Medicine
Education & Training
- BS, Biochemistry, University of Nancy (France)
- MS, Microbiology, University of Nancy (France)
- PhD, Immunology, University College London
- Fellowship: Stanford University
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William Black Medical Research Building
- (212) 305-4735
- Lab Phone:
- (212) 305-4735
- 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).
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]
- G4020 Graduate Immunology "Autoimmunity" (Spring 2014, 2015)
- G6055 Advanced Topics in Microbiology & Immunology "Novel concepts in the regulation of immune tolerance" (Fall 2014, 2015)
- G6004 Graduate Pathology "Immune mechanisms in the destruction of beta cells" (Spring 2015)
- M5108 The Body in Health and Disease, Immunology (Preceptor, Winter 2016)
Committees / Societies / Memberships
2009-present: Immunology of Diabetes Society
2015-present: Federation of Clinical Immunology Societies
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)
- Immune tolerance
- Type 1 diabetes
- Dendritic cells
Columbia Diabetes & Endocrinology Research Center (Pilot grant)
Role: PI (5% effort)
Funding period: 02/01/14-01/31/15 ($50,000 direct costs)
Title: Deciphering and visualizing epitope spreading in autoimmune diabetes.
The goal is to study cooperation between diabetogenic T cells in enabling epitope spreading.
NIH/NIAID, 1R21 AI117641-01
Role: PI (15% effort)
Funding period: 02/01/15-01/31/17 ($275,000 direct costs)
Title: Tolerance-inducing properties of human dendritic cell subsets in vivo.
The goal is to develop a humanized mouse model to study the tolerogenic function of several human dendritic cell subsets, particularly extrathymic AIRE-expressing cells.
NIH/NIAID, 1R21 AI110812-01A1
Role: PI (20% effort)
Funding period: 08/01/15-07/30/17 ($275,000 direct costs)
Title: Engineering and targeting novel antigen-specific tolerogenic interfaces
This study aims to engineer dendritic cells using combinations of mRNA-encoded products to enhance tolerogenic properties and targeting to specific sites in vivo.
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
DIABETES AND ENDOCRINOLOGY RESEARCH CENTER (Federal Gov)
Mar 15 2013 - 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
- Nato Teteloshvili, Postdoctoral Research Scientist
- Larry Le, Technician / lab manager
- Jorge Postigo, Postdoctoral Research Scientist
Columbia University collaborators:
Yong-Guang Yang, Donna Farber, Megan Sykes, Lance Kam, Li Qiang, Yufeng Shen
Current outside collaborators:
Mark Anderson, UCSF
Jack Lin, Anvil Biosciences
- Creusot RJ, Battaglia M, Roncarolo MG, Fathman CG. Cell-based therapies and other non-traditional approaches for Type 1 diabetes. Stem Cells (in press).
- 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