Ivan CRUZ MOURA
  • E-mail :[email]
  • Phone : +33 1 42 75 42 85
  • Location : Paris, France
Last update 2016-01-15 14:49:09.666

Ivan CRUZ MOURA PhD in Immunology

Course and current status

2015               INSERM admission as “directeur de recherche de 2ème classe” (1st January 2015)

2011                INSERM admission as “chargé de recherche de 1ère classe” (1st January 2011) 

2007                INSERM tenured as “chargé de recherche de 2ème classe” (1st November 2007)

2006                INSERM admission as “stagiaire chargé de recherche de 2ème classe” (1st November 2006)

2005-2006     Necker Hospital: Post-doctoral fellow, CNRS UMR 8147, supervisor Professor Olivier Hermine.

2003-2005     Curie Institute: Post-doctoral fellow, INSERM U520, supervisor Dr Olivier Lantz.

2002-2003     Bichat School of Medicine: Ph.D. Immunology, INSERM E0225, director Dr. Renato C Monteiro.

2000-2002     Necker Hospital: INSERM U-25, director Pr. Jean-François BACH.

1999-2000     Pasteur Institute: Laboratory of Malaria, director Dr. Catherine Braun BRETON.  

1992-1999     University of Sao Paulo – Laboratory of Malaria, supervisor Dr. Julio PUDLES. 

Scientific summary

Erythropoiesis is a fascinating system to understand cell proliferation survival and differentiation. Growth factors (SCF during early erythropoiesis and Epo during late erythropoiesis) are absolutely required for cell survival and proliferation allowing the program of differentiation to occur. Transferrin receptor 1 (CD71/TfR1) is essential for erythropoiesis the investigation of TfR1 function has been focused on its undeniable role in iron metabolism. However, recent data demonstrate that TfR1 is a multi-ligand receptor that participates in a wide array of cellular functions. We have identified TfR1 as a receptor for A1 isotype immunoglobulins (IgA1). We have shown that pIgA1s are able through their interaction with the TfR1 to stimulate erythropoiesis by sensitizing erythroblasts to Epo.

TfR1 expression is correlated with cancer progression and prognosis. Acute myeloid leukemia (AML) is a heterogeneous malignant disorder originating from mutations in progenitor cells that lead to the unrestrained proliferation of undifferentiated myeloblasts. We have shown that iron homeostasis controls monocyte differentiation in normal myelopoiesis and AML. Moreover, iron deprivation agents synergized with vitamin D (VD) to induce MAPK/JNK activation and VDR expression that leukemia progression. In retrospective studies this combined therapy was effective in AML patients. Therefore iron availability modulates myeloid cell commitment and targeting this pathway together with conventional differentiating agents would provide new therapeutic modalities for AML.

Recently, we have been interested in the pathophysiology of thalassemia. We identified growth differentiation factor 11 (GDF11), a TGF-b family member, as a key molecule participating in the pathogenesis of ineffective erythropoiesis in this disease. GDF11 expression was increased in spleen erythroblasts from thalassemic mice and in erythroblasts and sera from ß-thalassemic subjects. Inactivation of GDF11 by an Activin receptor IIa (ActRIIa) ligand trap, decreased oxidative stress and α-globin membrane precipitates resulting in increased terminal erythroid differentiation. This resulted in improved ineffective erythropoiesis, correction of anemia and limited iron overload in thalassemic mice. Moreover, encouraging results have been observed in a clinical trial in thalassemic patients. Altogether these results open new perspectives in the understanding of normal and pathological hematopoiesis and lead to propose innovative treatments for anemia.

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