Remi J. Creusot, PhD

Profile Headshot

Overview

Academic Appointments

  • Assistant Professor of Medical Sciences (in Medicine)

Administrative Titles

  • Principal Investigator, Columbia Center for Translational Immunology
  • Principal Investigator, Naomi Berrie Diabetes Center
  • Director, CCTI and Herbert Irving Comprehensive Cancer Center Flow Cytometry Core
  • Director, Diabetes Research Center Flow Cytometry and Cell Sorting 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.

Languages

  • French

Credentials & Experience

Education & Training

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

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

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.

Research Interests

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

Grants

nPOD / Helmsley Charitable Trust, George Eisenbarth Award for nPOD Team Science (Creusot Subcontract PI)

01/01/19 – 12/31/19  ($26,950)

NIH/NIAID, R01 AI142428-01 (Creusot PI)

11/15/18 – 10/31/23 ($1,250,000)

In vivo development and reactivity of human autoreactive T cells

NIH/NIDDK, P30 DK063608 (Creusot Core Leader)

02/01/08 – 01/31/23 ($92,000)

Diabetes & Endocrinology Research Center.Role: Core leader (10%)

IN VIVO DEVELOPMENT AND REACTIVITY OF HUMAN AUTOREACTIVE T CELLS (Federal Gov)

Nov 15 2018 - Oct 31 2023

MODELING AUTOIMMUNE PATHOGENESIS AND BETA CELL DESTRUCTION BY T1D IMMUNE SYSTEMS (Federal Gov)

Sep 20 2019 - May 31 2023

THYMIC SELECTION OF HUMAN DIABETOGENIC T CELLS (Private)

Mar 1 2020 - Feb 28 2023

COLUMBIA DIABETES RESEARCH CENTER (Federal Gov)

Jul 6 2018 - Jan 31 2023

RE-ESTABLISHING IMMUNE TOLERANCE AGAINST MULTIPLE CELL ANTIGENS USING NOVEL EPITOPE DELIVERY APPROACHES (Private)

Jan 1 2019 - Dec 31 2021

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

Jan 1 2018 - Dec 31 2020

CANCER CENTER SUPPORT GRANT (Federal Gov)

Jul 1 2014 - Jun 30 2020

EXACERBATED EXPRESSION OF CYTOTOXIC GENES IN THE PLNS OF T1D PATIENTS (Private)

Jan 1 2019 - Dec 31 2019

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

Selected Publications

Li Y, Teteloshvili N, Tan S, Rao S, Han A, Yang YG, Creusot RJ. Humanized mice reveal new insights into the thymic selection of human autoreactive CD8+ T cells. Front. Immunol. 2019; 10:63 (Epub 02/04/2019).

Postigo-Fernandez J, Creusot RJ. A multi-epitope DNA vaccine enables a broad engagement of diabetogenic T cells for tolerance in Type 1 diabetes. J. Autoimmun. 2018; 98:13-23 (Epub 11/17/18).

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.