CV Science

Claire Vandiedonck PhD in Genetics, Associate Professor of Biostatistics

Course and current status

 Contact Details

Inserm UMR-S-958 “Genetics of diabetes”
University Paris Diderot - Paris 7
School of Medicine
Site Villemin
10 avenue de Verdun
75010 Paris, France
phone: +33(0)157278555
email: claire.vandiedonck@inserm.fr 

Positions

• Current:            Associate Professor of Biostatistics, University Paris Diderot, INSERM UMRS-958
• 2009-2011:      Advanced Postdoctoral Scientist, INSERM UMRS-958, University Paris Diderot
• 2005-2009:      Post-Doctoral Scientist at the Wellcome Trust Centre for Human Genetics, lab of Dr JC Knight, Oxford University (http://www.well.ox.ac.uk/knight-j) 
• 1999-2005:      D.Phil at INSERM U580 of HJ Garchon, University Paris Descartes

Education and degrees

• 2004:   Ph.D. thesis in Genetics/Immunology, University Paris Descartes
• 2000:   Advanced Diploma (M2) of Molecular Genetics, University Paris Descartes
• 1999:   M. Sc. in Cell Biology and Physiology, University Pierre & Marie Curie
• 1998:   B.Sc. in Cell Biology and Physiology, University Pierre & Marie Curie

Teaching

• 2012-2013: Genomics for M2 students in bioinformatics including a "RNA-Seq data analysis course"; Biostatitics for 1st-year medical studentds at Paris Diderot; Biostatistics for L2 and L3 at Paris Diderot; Genomics for master 2 (M2) students at Paris Diderot
• 2011-2012: Biostatistics for 1st-year medical students at Paris Diderot; Biostatistics for L2 and L3 students at Paris Diderot; Genomics for M2 students at Paris Diderot
  
• 2010-2011: Biostatistics for L3 students at Paris Diderot
  

 Memberships

• Type 1 Diabetes Genetics Consortium
• Société Française d’Immunologie
• American Society of Human Genetics

 Research grants

• 2012-2013: JDRF Transition Award
  
• 2009-2013: NIH Type 1 Diabetes Impact Award (DP3)
  
• 2010-2011: PHC Alliance between France and UK
  
• 2009-2012: JDRF Advanced Postdoctoral Fellowship
  

Scientific summary

Research interest

My main research interest is the genetics of autoimmune diseases, focusing on their prime genetic factor, the human Major Histocompatibility Complex (MHC). My work is situated at the interface of mutifactorial genetics, genomics and transcriptomics. It involves both "wet lab" and bioinformatics to analyze high-throughput data using eQTL mapping strategies.

Keywords: immunogenetics, MHC, autoimmunity, type 1 diabetes, eQTL mapping, multifactorial genetics, biostatistics    

Current project

My current project aims at identifying new MHC genes involved in the susceptibility to type 1 diabetes using a genetical genomics approach that combines genetic studies and high-throughput functional genomics approaches. More specifically,  I use transcriptomic data and eQTL mapping to identify MHC genes differentially expressed on haplotypes having opposing effects on the disease risk.

This research is supported by the Juvenile Diabetes Research Foundation, the NIH and the PHC-Alliance.  

Collaborations

Dr Julian Knight (Wellcome Trust Centre for Human Genetics, Oxford University)
Type 1 Diabetes Genetics Consortium 

Research history

I obtained a Ph.D in genetics from the University Paris Descartes in France in 2004. I was working in the laboratory of Dr Henri-Jean Garchon, where I analyzed the multifaceted role of the MHC in the genetic predisposition to acquired autoimmune myasthenia gravis and in the regulation of autoantibody expression (Vandiedonck et al. 2004, PNAS; Vandiedonck et al. 2005, J Autoimmunity).  I also reported the first association of the gene PTPN22 with the disease (Vandiedonk et al., 2006, Ann Neurol) and I identified an association of HLA-A with the disease form associated with a thymoma (Vandiedonck et al. 2009, J Neuroimmunol). Finally, I participated in the study of the gene encoding the target autoantigene CHRNA1 that revealed a new mechanism of central tolerance breakdown involving IRF8 and AIRE (Giraud et al. 2007, Nature).

In the MHC region, the final identification of the causal variants has been rendered difficult by the linkage disequilibrium that extends over long distances. Analysis of modification of MHC gene expression appears then as a necessary complement to help identify the disease variants. With this perspective in mind, I joined in 2005 the laboratory of Dr Julian Knight (http://www.well.ox.ac.uk/knight-j) (Wellcome Trust Centre for Human Genetics, Oxford University) as a postdoctoral scientist. There, using a custom array accounting for MHC polymorphism, I generated the first strand-specific haplo-spliceo-transcriptome map of the MHC (access the map here). This study revealed abundant haplotypic differences in gene expression and that alternative splicing is more frequent in the MHC than genome-wide (Vandiedonck et al., 2011, Genome Research).

I have also had a special interest in studying the expression of two emblematic genes of the MHC central class III region, the TNF and LTA (Taylor et al, 2008, NAR) and was involved in the development of strategies to investigate allele-specific expression (Campino et al, 2008, PLoS One; Holt et al., 2011, J Allergy Clin Immunol).

In July 2009, I came back to France where I joined the research laboratory Inserm UMR-S-958 "Genetics of diabetes" of Dr Cécile Julier. After a senior postdoc position, I obtained a permanent position as Associate Professor of Biostatistics. During my research time, I conduct a project applying the genetical genomics approach to type 1 diabetes.

Team members:

• Saffarian Azadeh, postdoc in bioinformatics/algorithmics
• Bourmaud Morgane, assistant engineer in molecular biology
• Stephen Tharshana, master 2 student in genetics 

Alumni
• Zhao Xia, master 2 student in genetics and medical student (back to her medical school in Shanghai)
• Rezaei Neda, master 2 student in biology (now research engineer in Iran)
• Luscap Windy, master 2 student in bioinformtics (now research engineer at Cochin Institute) 

The team in June 2012 (from left to right: Neda Rezaei, Claire Vandiedonck, Windy Luscap, Azadeh Saffarian)

Selected publications : 

Vandiedonck C, Taylor MS, Lockstone HE, Plant K, Taylor JM, Durrant C, Broxholme J, Fairfax BP and Knight JC (2011) Pervasive haplotypic variation in the spliceo-transcriptome of the human MHC. Genome Research, 2011 Jul ; 21(7) :1042-54 [PMID:21628452].

Cover artpainted by Françoise Vandiedonck
(click here for a more resolutive picture):

 Comment in :
Muers M  (2011) Complex disease: ups and downs at the MHC.
Nature review genetics, 2011 Jun 17 ; 12(7) :456-7 [PMID:21681207].

Vandiedonck C and Knight JC (2009). The human Major Histocompatibility Complex as a paradigm in genomics research. Brief Funct Genomics, 2009 Sep;8(5):379-94 [PMID:19468039].

Vandiedonck C, Raffoux C, Eymard B, Tranchant C, Dulmet E, Krumeich S, Gajdos P, Garchon HJ (2009) Association of HLA-A in autoimmune myasthenia gravis with thymoma. J Neuroimmunol, 2009 May 29;210(1-2):120-3 [PMID:19278738]

Taylor JM, Wicks K, Vandiedonck C, Knight JC (2008) Chromatin profiling across the human tumour necrosis factor gene locus reveals a complex, cell type-specific landscape with novel regulatory elements. Nucleic Acids Res, 36(15):4845-62 [PMID:18653526]

Giraud M, Taubert R, Vandiedonck C, Ke X, Levi-Strauss M, Pagani F, Baralle FE, Eymard B, Tranchant C, Gajdos P, Vincent A, Willcox N, Beeson D, Kyewski B, Garchon HJ (2007) An IRF8-binding promoter variant and AIRE control CHRNA1 promiscuous expression in thymus. Nature, 448:934-937 [PMID:17687331]

Vandiedonck C, Capdevielle C, Giraud M, Krumeich S, Jais JP, Eymard B, Tranchant C, Gajdos P, Garchon HJ (2006) Association of the PTPN22*R620W Polymorphism with Autoimmune Myasthenia Gravis. Annals of Neurology, 59:404-407 [PMID:16437561]

Vandiedonck C, Beaurain G, Giraud M, Hue-Beauvais C, Eymard B, Tranchant C, Gajdos P, Dausset J, Garchon HJ (2004) Pleiotropic effects of the 8.1 HLA haplotype in patients with autoimmune myasthenia gravis and thymus hyperplasia. Proc Natl Acad Sci U S A, 101:15464-15469 [PMID:15489265]

My current h-index is: 8

For a complete list of my publications, follow the PubMed link.