thierry walzer
  • E-mail :[email]
  • Phone : +33 4 37 28 23 73
  • Location : Lyon, France
Last update 2018-06-28 09:55:26.738

thierry walzer PhD Immunology

Course and current status

Since 2009 :
-Head of the lab “Innate Immunity in infectious and autoimmune diseases” at the CIRI (Centre international de recherche en infectiologie). 21 avenue Tony Garnier, 69007 Lyon, France
-Coordinator of the Immunology specialty at the CIRI

2004 – 2009 : Centre d’Immunologie de Marseille-Luminy (CIML)
Lab “Natural Killer cells and innate immunity”
Principal investigator, in the lab headed by Pr Eric VIVIER.

2002-2004 Amgen Inc., Seattle, WA, USA.
Postdoc: “poxvirus semaphorin A39R binds to plexin C1 and inhibits dendritic cell function”

1999-2002  Ecole Normale Supérieure de Lyon
PhD Thesis : “molecular characterization of memory CD8 T cells”  MRT grant.
Thesis director: Dr Jacqueline Marvel.

Scientific summary

I  head a team of about 20-25 persons entitled “innate immunity in infectious and autoimmune diseases” composed of four subgroups:

1 – Differentiation and migration of NK cells (PI: T Walzer, TW)

2 – Activation and metabolism of NK cells (PI: Antoine Marçais, AM)

3 – Innate immunity in chronic infections (PI: Uzma Hasan, UH)

4 – Genetics of pediatric-onset lupus (PI: Alexandre Belot, AB)

Our main research interests are 1) the molecular pathways that underlie the differentiation, migration and activation of immune effectors and 2) how genetic or acquired modifications in these pathways may lead to immune deficits or to autoimmune reactions. Our main achievements in the past years are the following:

1) the elucidation of the role of the transcription factors (TF) Zeb2 and Eomes in Natural Killer (NK) cell maturation. Zeb2 expression is induced at late stages of maturation by another TF, T-bet, and sustains the transcriptional activity of T-bet, in a classical feed forward loop. T-bet and Eomes have similar DNA-binding domains (T-box). Using novel Eomes-GFP reporter mice, we discovered that T-bet is expressed on both NK cells and the closely related lineage innate-lymphoid cell type 1 (ILC1), while Eomes expression specifies the NK cell lineage.

2) the elucidation of the role of S1P5 in NK cell migration. In both mouse and human, NK cells develop in the bone marrow, and their exit from this compartment to the blood circulation is dependent on the engagement of S1P5, a chemotactic receptor that recognizes sphingosine-1 phosphate vehicle by albumin in the blood and lymph.

3) the identification of the role of mTOR in NK cell activation. By using genetic and pharmacological approaches, we found that mTOR was essential for NK cell development, maturation and activation of NK cells. mTOR is regulated by many pathways in NK cells including cytokines like IL-15 and TGF-beta but also activating NK cell receptors. When activated, mTOR boosts NK cell bioenergetics metabolism, and amplifies signaling through activating receptors, thereby sustaining NK cell activation.

4) the impact of chronic infection or tumorigenesis on NK cell function. We found that peripheral NK cells from chronic hepatitis B carriers or tumor-bearing individuals had an exhausted phenotype, combining activation markers and reduced effector functions. They also have a reduced mTOR activity, suggesting that a negative impact of tumors or infections on this pathway may promote NK cell exhaustion.

5) the identification of novel genetic causes of lupus. We built a national cohort of pediatric-onset systemic lupus erythematosus (SLE). Using exome sequencing in familial cases, we identified several causal mutations in genes encoding PRKCD, IKAROS and LYN. We also identified many other putative causes of lupus. For the latter mutations, we generated several mouse models bearing the mutations identified in patients that helped us confirming or infirming the causality of the mutations and studying the underlying immunological mechanisms.

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