Ana CUMANO M.D.

Course and current status

Nationality : Portuguese.

Education :

1980 : Degree of Doctor in Medicine.

Professional experiences :          

1983-1987 : Post-doctoral training at the Genetics Institute in Cologne - Germany under the supervision of Prof. Klaus Rajewsky.

1987-1991 : Post-doctoral training at the Ontario Cancer Institute in Toronto - Canada, under the supervision of Prof Christopher J. Paige.

1992-1998 : Group leader at the Unité de Biologie Moléculaire du Gène directed by Prof. Philippe Kourilsky, at the Pasteur Institute Paris - France.  

1994-1997 : Tenure position as a research scientist at INSERM (Medical Research Council).

1997-2006 : Director of research 2 at INSERM.

1998-:           Head of the unit « Unité du Développement des Lymphocytes »-“Lymphopoiesis”, at the Pasteur Institute - Paris.

2002-2015 : Directeur de Recherche at the Pasteur Institute - Paris

2007-2015 : Director of research 1 at INSERM.

2016- :          Director of research “Classe Exceptionnelle” at INSERM

2016- :          Professor at the Pasteur Institute - Paris

Activities of international expertise :

2000-2014 : Member of the European Molecular Biology Organization (EMBO).

2007-2009 : Member of Agence d’Evaluation de la Recherche et de l’Enseignement Supérieur (AERES)

2009-2011 : Member of Commission Nationale ARC « Immunologie, microbiologie, hématopoïèse »

2009-2013 : Member of Scientific Council Pasteur Institute - Paris

2012-2014 :Vice-presidente of Commission Nationale ARC « Immunologie, microbiologie, hématopoïèse »

2014- :          Member of COMESP Pasteur Institute – Paris

2014- :          Member of Advisory Board SRC, Stockholm, Suède

2015- :          co-director Immunologie Approfondie course M2 at the Pasteur Institute - Paris.

2015- :          panel member ERC Advanced grants

Scientific Prizes :

• Prix Lacassagne 2004 du Collège de France
• Prix Georges Zermati 2004 de la Fondation Georges Zermati
• Prix « seeds of science » 2011 - Portugal

Scientific summary

Project title : LYMPHOID LINEAGE COMMITMENT DURING MOUSE EMBRYONIC DEVELOPMENT

I have 30 years of research experience in Immunology, mostly dedicated to the study of the development of the immune system, I have more than 150 indexed publications and my work has been cited more than 9.000 times.

1. The molecular basis of the high affinity of secondary immune response antibodies.

In the laboratory of Klaus Rajewsky, I found that in the NP-CGG immunization system, one single somatic mutation (alanine to leucine) in the first hypervariable region was sufficient to increase the affinity to antigen, from a primary to a secondary immune response. This mutation was present in the majority of the independent clones. Many mutations occurring before and after the acquisition of increased affinity were bystanders and did not concur to the antigen binding capacity of secondary antibodies.

2. The origin of B lineage cells.

In the laboratory of Christopher J. Paige, I developed culture conditions that allowed in vitro differentiation of B and myeloid cells from single hematopoietic progenitors and found that B cells were originated from fetal liver progenitors that maintained macrophage but no neutrophil or erythrocyte differentiation potential. This work also revealed Interleukin 7 (IL-7) as a major trophic factor for lymphocytes.

3. The origin of HSCs.

In the laboratory of Philippe Kourilsky, at Pasteur, I found the first evidences of the origin of mammalian hematopoietic stem cells.

4. Immature HSCs.

Since the creation of the Unit I direct at Pasteur, I found that hematopoietic stem cells are generated as immature cells and defined the conditions they required for reconstitution of the hematopoietic system.

 5. The immune system.

Understanding the mechanisms that regulate the adult immune system requires understanding how it is established, during late embryonic and neonatal life. The interest devoted to understanding the molecular basis for lymphocyte lineage commitment comes from this conviction.

We found 1. Interleukin-7 has a role not only in cell fate (survive, expand or die) but also in lineage commitment and the underlying molecular mechanism 2. Fetal common lymphoid progenitors comprise cells engaged in the NK/ILC and in the B/NK pathways of differentiation, defined their phenotype and the underlying molecular mechanisms. More recently we found that HSA could discriminate in fetal liver common lymphoid progenitors three subsets corresponding, multipotent lymphoid progenitors or to partial committed cells into the T or the B pathways of differentiation. 3.We found that the mouse thymus is colonized by successive waves of progenitors TSP-1 and TSP-2 that differ in their function and stage of differentiation. Consistently, the differentially expressed transcripts, represented the highest in TSP-1, are tumor suppressor genes, cell cycle regulators and genes from the imprinted gene network. H19, an imprinted long non-coding RNA with a particularly high expression in TSP-1, is a trans-regulator of the imprinted gene network that has tumor suppressor functions.

The project I propose derives from these observations. My objectives are:

A. Understanding the molecular basis for the initial stages of lymphoid lineage commitment in the FL that give rise to the first TSP.

B. A detailed characterization of the different T cell populations generated by TSP-1 and TSP-2.

C. Determining the molecular cues that modulate the properties of TSP-1 and TSP-2: the role of cell cycle regulators, tumor suppressor genes and the imprinted network.

D. The evaluation of the impact of the cells originated from each wave in establishing the mature immune system.