Home Research Multi-factorial diseases C. Nguyen

Dr Catherine Nguyen

Director of inserm-AMU UMR 1090 « Technologie Avancée pour le Génome et la Clinique »

Co-leader of TGML



This e-mail address is being protected from spambots. You need JavaScript enabled to view it

tel. +33(0)4 91 82 87 02


Research interests

My research interest is to elucidate the molecular regulatory mechanisms sustaining biological functions. This being achieved by aggregating the skills and knowledge in these diverse components in order to create a synergy around a biological project. Malaria, sepsis, and cancers are multifactorial diseases influenced by genetic and environmental factors. We aim at identifying genetic variants and/or deregulated networks associated with the diseases.

In this context: on the one hand, we extend the use of the emerging integrative biology approaches to study pathologies such as cancers and severe sepsis in close association with hospital partners; on the other hand, we aggregate high throughput approaches issue from the genomic, classical biological methods, technological development and bioinformatics analysis to identify the functions of one gene in different organs.


1- Deciphering the molecular basis of Haemato-Immunological complex diseases: The complex control of gene expression during sepsis: from man to mouse to man.



Investigators: Séverine Garnier, Béatrice Loriod, Régis Costello, Pascal Rihet, and Catherine Nguyen,

Internal collaborators: Denis Puthier, Christine Brun, Carl Herrmann, François-Xavier Théodule, Jacques van Helden

Other collaborators: Sophie Debentzman (CNRS 9027), Anaïs Baudot (IML), Patrick Trieux Cuot, Pasteur Institute, Paris


Sepsis in neutropenic patients: Little progress has been made in deciphering the articulation between a non-infectious inflammation and the outcome of a subsequent infection. This project originally started in collaboration with intensive care with sepsis patients following a serious traumatism, are now pursued with neutropenic patients to predict, for each patient, a profile linked to a higher risk of infection and/or severe sepsis. Treatment of cancer, and more particularly of haematological malignancies, partly relies on chemotherapy. Most therapeutic regimens display various toxicities, one of the most common being haematological toxicity, affecting the three lineages. While anemia and thrombopenia can be overcome by haematological growth factors and transfusion, one of the most severe life-threatening toxicity is sepsis that develops during neutropenia. As consequence: (1) at the bedside of patients exhibiting inflammation, the diagnosis of sepsis remains challenging; and, (2) sepsis in neutropenic patients is probably different from “classical” sepsis since in the absence of neutrophils (and monocytes) the inflammatory profile is certainly different, reflecting the clinical differences.

The aims are: to identify genes involved in these mechanisms in order (i) to identify new potential therapeutic targets; (ii) to understand their functions in the response to infection; (iii) to use these data in the context of integrated analyses taking into account all the parameters leading to inappropriate answers (expression, polymorphism, interaction…) leading to a higher risk of infection and/or severe sepsis.

Sepsis in mouse models: We develop an approache based on the Acute Lung Injury (ALI) in mice in order to decipher the inflammation/ infection stages. Acute Respiratory Distress Syndrome (ARDS) is the last stage of an acute inflammatory process that affects the respiratory system. It carries a high mortality rate (40-50%). An important cause of ARDS is sepsis, which associates inflammation and infection. It seems that, in sepsis, the timing of cytokine release and the balance between pro- and anti-inflammatory agents determine the severity of infection. Their excessive production may be associated with deleterious effects.

Our aims are to set up a strategy allowing uncoupling the infection from the inflammation essentially by setting up an animal model in which each stage of the inflammation and the infection processes can be controlled independently. This will allow us to test whether an infection occurring over an inflammatory state overwhelmed the inflammation regulatory mechanisms, then possibly explaining the ultimate failure of organs in severe diseases.

Sepsis and malaria: In malarial disease, the manifestation generally differs from person to person and may range from asymptomatic parasitemia or mild malaria, to severe anaemia, severe respiratory distress, or cerebral malaria (CM). Our underlying hypothesis is the existence of common molecular networks involved in both malaria and bacterial sepsis. Several lines of evidence support this hypothesis: i) sepsis and malaria have been linked to a systemic inflammatory response, involving blood cells; ii) several genes or proteins have been shown to be involved in both diseases, such as TNF, TNFR2, TLR2, TLR4, or complement components; iii) lung dysfunction has been demonstrated both in malaria and bacterial sepsis.

Our aims are to determine specific and common gene expression profiles that would represent specific and common pathways in malaria and sepsis. We will compare transcriptional signatures in tissues taken from mice with sepsis versus mice with malaria to identify deregulated genes in both sepsis and malaria.

Overall, our projects approached the biological questions by large-scale experiments, leaning on the high-throughput genomic platform, and are strongly interconnected with an experienced biocomputing research team. The project should provide the community with: (i) new approaches to analyse animal models and protocols to study the impact and the interconnections between inflammation and infection; (ii) a dynamic map of the biological processes and the functional modules at work in each tested situation. We then expect to be able to identify on the one hand, the triggered networks when inflammatory processes are overwhelmed by infection, and on the other hand, the sub-networks responsible for the homeostasis of the inflammatory systems; (iii) a renewed and integrated view of the interconnections and the dependencies of inflammation and infection.

Ultimately, the results obtained during the course of this project, if applicable to human, may impact the diagnosis, the prognosis, therapy choices and eventually drug design.


Selected publications


1- Textoris J, Loriod B, Benayoun L, Gourraud PA, Puthier D, Albanèse J, Mantz J, Martin C, Nguyen C*, Leone M* Identification of a genetic signature of sepsis in severe trauma patients -SepsiChip Project phase I Anesthesiology. 2011 Aug;115 (2):344-52.

2-Barbier M, Faille D, Loriod B, Textoris J, Camus C, Puthier D, Flori L, Victorero G, Alessi MC, Fusaï T, Nguyen C, Grau G E, and Rihet P. Platelets alter gene expression profile in human brain endothelial cells in an in vitro model of cerebral malaria. PLoS One. 2011;6(5):e19651. Epub 2011 May 16.

3-Lesur I., J. Textoris, B. Loriod, C. Courbon, S. Garcia, M. Leone, Nguyen C.. Gene Expression Profiles Characterize Inflammation Stages in the Acute Lung Injury in Mice Gene expression of ALI in mice. PloS One 2010 Jul 8;5(7):e11485.

4-Lopez, F; Textoris, J; Bergon, A; Didier, G; Remy, E; Granjeaud, S; Imbert, J; Nguyen, C; Puthier, D. TranscriptomeBrowser: a powerful and flexible toolbox to explore productively the transcriptional landscape of the Gene expression Omnibus database PLoS ONE. 2008;3 (12):e4001.

5-Delahaye NF, Coltel N, Puthier D, Barbier M, Benech P, Joly F, Iraki F A, Grau G E Nguyen C and P Rihet. Gene expression analysis reveals early changes in several molecular pathways in cerebral malaria-susceptible mice versus cerebral malaria-resistant mice. BMC Genomics. 2007 Dec 6;8(1):452

6-Delahaye NF, Coltel N, Puthier D, Flori L, Houlgatte R, Iraqi FA, Nguyen C, Grau GE, Rihet P.Gene-Expression Profiling Discriminates between Cerebral Malaria (CM)-Susceptible Mice and CM-Resistant Mice. J Infect Dis. 2006 Jan 15;193 (2):312-21.


2- Functional characterization of the multifunctional Spatial/Tbata gene in mammals

Investigators: Miriam Yammine, Béatrice Loriod, Geneviève Victorero, Bach Hui Anh, Denis Puthier, Catherine Nguyen.

Internal collaborators: Christine Brun, Jean Imbert, Carl Hermann

External collaborators: Nelson Dussetti (UMR1068); Nathalie. Scholler (University of Pennsylvania); Catherine Guillemain, (the Conception Hospital); Bernard Jegou (GERHM-Inserm U.625, Rennes).


Using a transcriptomic approach to analyze mice thymus development we were able to virtually transcriptionally micro-dissect this organ [3], and selected a gene involved in thymic microenvironment that we called Spatial gene (Stromal Protein Associated with Thymii and Lymph-node) also known as Tbata (Thymus, brain and testes associated). Our previous studies suggest that Spatial is a multifunctional protein with different functions in different tissues or cells and possibly plays a role in masculine infertility, neurogenesis and thymic education as well as in cells morphogenesis.

The function of this gene raises several questions. On the one hand, different variants are expressed at different levels in highly polarized cells, suggesting that it would play a role in morphogenesis and\or motility. On the other hand, it seems that there is cooperation between isoforms to insure a particular function, for example in the thymus the various isoforms seem to play independent roles in morphogenesis and thymocytes education. In addition, Spatial is likely to be involved in different diseases. Thus, it seems to be a good candidate to explain different diseases phenotypes through its variants. Spatial is a typical example of a gene with different variants expressed at different levels in different tissues leading to different functions. Thus, it is a candidate to experimentally explore multifunctionality/moonlighting behavior at the level of its interaction network in collaboration with C. Brun (Axis 3). All these questions will be approached with the tools of the genomics, leaning on well identified expertises (internal and external collaborations).

Our aims are:

1- To decipher Spatial functions in morphogenesis, using high throughput transcriptome approaches in neuronal cell models after gene knock down by siRNA.

2- To identify the Spatial protein partners based on a yeast two-hybrid approach. Identification of Spatial protein partners is currently performed on different Spatial isoforms (Collaboration Nelson Dussetti). The protein-protein interaction network around Spatial will be investigated in collaboration with C. Brun (Axis 3). In collaboration with Dr. N. Scholler we produce a biotinylated isoform-specific antibodies. This will allow (i) investigating the specific subcellular distribution of each Spatial variant and (ii) validating their protein interactors via immunoprecipitation.

3- To identify the transcription factors, which regulate Spatial. A bioinformatics analysis predicts -in conserved non coding regions of the Spatial gene- a motif for the binding of a transcription factor of the RFX family, known to be involved in cilia and flagella regulation . To identify the transcription factors, which regulate Spatial. We will use chromatin immunoprecipitation (Chip) approaches (collaboration J. Imbert) to test this hypothesis.

4- To study Spatial in human models, and have found that the human Spatial gene as being associated with spermiogenesis . Preliminary results suggest that Spatial is indeed associated with masculine infertility (collaboration Dr. Catherine Guillemain), leading to a collaboration on this last subject.

Selected publications

1. Saade,M., Irla,M., Yammine,M., Boulanger,N., Victorero,G., Vincentelli,R., Penninger,J.M., Hollander,G.A., Chauvet,S., and Nguyen,C. Spatial (Tbata) expression in mature medullary thymic epithelial cells, Eur J Immunol. 2010 Feb;40(2):530-8.

2. Irla M, Saade M, Fernandez C, Chasson L, Goulhen F, Victorero G, Dahman N, Chazal G and Nguyen C. Neuronal distribution of Spatial in the developing cerebellum  and hippocampus and its somatodendritic association with the kinesin motor KIF17. Exp Cell Res. 2007 Dec 10;313(20):4107-19. Epub 2007 Sep 20.

3. Saade M, Irla M, Govin j, Goulhen F, Victorero G, Samson M and Nguyen C. Dynamic distribution of Spatial during mouse spermatogenesis and its interaction with the kinesin KIF17b. Exp Cell Res. 2007 Feb 1;313(3):614-26..

4. Puthier D, Joly F, Irla M, Saade M, Victorero G, Loriod B,and Nguyen C. New insights into thymocyte differentiation by transcriptional analysis of knockout mouse models.  J Immunol. 2004 Nov 15;173(10):6109-18

5 Irla M, Puthier D, Granjeaud S, Saade M, Victorero G, Mattei  MG and C F Nguyen. Genomic organization and the tissue distribution of alternatively spliced isoforms of the mouse Spatial gene  BMC Genomics. 2004 Jul 05;5(1):41.

6. Irla M, Puthier D, Le Goffic R, Victorero G, Freeman T, Naquet P, Samson M and C Nguyen. Spatial, a new nuclear factor tightly regulated during mouse spermatogenesis. Molecular of Development GEP, 2003, May;3(2):135-8. Molecular of Development GEP Erratum in: Gene Expr Patterns. 2003 Aug;3(4):539

7.Carrier A, Nguyen C, Victorero G, Granjeaud S, Rocha D, Bernard K, Miazec A, Ferrier p, Malissen M, Malissen B and Jordan BR. Differential gene expression in CD3- epsilon and Rag-1 deficient thymuses : Definition of a set of genes potentially involved in thymocyte maturation. Immunogenetics, 1999, 50:255-270