Publish at 18.11.2019
Presentation
The common denominator of our project is the human lymphohaematopoietic system, characterized by cells with differing self-renewal and differentiation capacities as a function of the individual's age and clinical status (i.e. healthy or diseased). In adult mammals, haematopoiesis (i.e. the expansion and differentiation of haematopoietic stem cells into blood cells in the bone marrow) undergoes constant, tightly regulated renewal and undergoes profound changes over the lifespan.
Understanding of the hierarchy of human haematopoiesis and the different steps in T and B cell differentiation in the healthy body and in very particular disease situations constitutes the most fundamental part of our research project. To lead our research, the human lymphohematopoiesis laboratory has access to a cohort of patients involved in phase I/II gene therapy clinical trials and also a cohort of patients with hereditary immune deficiencies associated with B cells. Overall, the knowledge generated by these studies will help us to actively implement new treatment protocols. Haematopoietic stem and progenitor cells (HSPCs) harvested from a healthy or diseased individual and ex vivo gene modifications constitute essential tools for curing most severe, cell-intrinsic, inherited defects of the lymphohaematopoietic system. Nevertheless, several issues still compromise the full success of these types of therapies.
Improvements in this HSPC-based strategy have resulted from progress and discoveries provided by the first part of our project and by other research groups. The most recent findings on the characteristics of human T cells (i.e. their long life, self-renewal capacity, homeostasis and functions) have prompted us and others to consider their in vivo use after ex vivo manipulation - paving the way for less toxic therapeutic approaches.
Team
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Isabelle André
Laboratory Director
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Marina Cavazzana
Professor in Haematology, Head of the Biotherapy Department, Director of the Clinical Investigation Center for Innovative Therapies
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Boris BESSOT
Engineer
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Tifanie BLEIN
Engineer
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Soëli CHARBONNIER
Engineer
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Loïc CHENTOUT
Engineer
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Corinne de Chappedelaine
Laboratory Manager
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Adeline DENIS
Engineer
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Anne DURANDY
Emeritus Research Director
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Alexandrine GARRIGUE
Engineer
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Pierre GAUDEAUX
PhD Student
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Akshay JOSHI
Postdoctoral fellow
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Sven KRACKER
Research Director
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Chantal LAGRESLE-PEYROU
Projects Manager - Researcher
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Ranjita MOIRANGTHEM
Postdoctoral fellow
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Nidia MORENO
Postdoctoral Fellow
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Inès RAJBAOUI
Financial Manager
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Emmanuelle SIX
Researcher
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Steicy SOBRINO
Post-doc
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Nataël SOREL
Engineer
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Romane THOUENON
PhD Student
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Hélène VINÇON
Engineer
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Julien ZUBER
MD-PhD, PU-PH
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Lucie POGGI
Post-Doctorante
Resources & publications
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Blood Adv 2021
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Mol Ther Methods Clin Dev
A Nontoxic Transduction Enhancer Enables Highly Efficient Lentiviral Transduc...
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Nat Rev Drug Discov 2019
Gene therapy targeting haematopoietic stem cells for inherited diseases: prog...
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J. Allergy Clin. Immunol.
Generation of adult human T-cell progenitors for immunotherapeutic applications.
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Hum. Gene Ther. 2016
Gene Therapy for X-Linked Severe Combined Immunodeficiency: Where Do We Stand?
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J. Clin. Invest. 2019
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J. Allergy Clin. Immunol. 2017
Clinical and immunologic phenotype associated with activated phosphoinositide...
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J. Clin. Invest. 2015
A human immunodeficiency caused by mutations in the PIK3R1 gene.
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J. Allergy Clin. Immunol.
X-linked primary immunodeficiency associated with hemizygous mutations in the...
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Cell Death Dis 2016
AK2 deficiency compromises the mitochondrial energy metabolism required for d...
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J Allergy Clin Immunol. 2018
Clinical spectrum and features of activated phosphoinositide 3-kinase δ syndr...
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J Clin Immunol 2017
Neutropenia in Patients with Common Variable Immunodeficiency: a Rare Event A...
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J Allergy Clin Immunol 2021
Improving the diagnostic efficiency of primary immunodeficiencies with target...
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Mol Ther Methods Clin Dev
Successful Preclinical Development of Gene Therapy for Recombinase-Activating...
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Front Pediatr 2019
Hematopoietic Stem Cell Transplant for the Treatment of X-MAID.
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Mol Ther Methods Clin Dev
A Nontoxic Transduction Enhancer Enables Highly Efficient Lentiviral Transduc...
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J Allergy Clin Immunol 2015
An in vivo genetic reversion highlights the crucial role of Myb-Like, SWIRM, ...
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J Allergy Clin Immunol 2014
The BLNK adaptor protein has a nonredundant role in human B-cell differentiat...
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J Allergy Clin Immunol 2014
Successful RAG1-SCID gene therapy depends on the level of RAG1 expression.
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J Allergy Clin Immunol 2014
Recombination-activating gene 1 (Rag1)-deficient mice with severe combined im...
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Bone Marrow Transplant 2019
Ex vivo generated human T-lymphoid progenitors as a tool to accelerate immune...
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Stem Cells Dev. 2017
Gene Therapy with Hematopoietic Stem Cells: The Diseased Bone Marrow's Point ...
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Am J Transplant 2020
Donor-targeted serotherapy as a rescue therapy for steroid-resistant acute GV...