CV Science

Francoise Homo-Delarche MD, PhD

Course and current status

Francoise Homo-Delarche

Personal

                   Date of birth:                      June 16, 1950

                    Place of birth:                     Paris, France

Education

 1975                                      MD, University of Paris VI, France  

 1975                                      Immunology certificat, Pasteur Institute                   

 1981                             PhD, University of Paris VII, France

Present position

Centre de Recherche des Cordeliers

INSERM UMRS 1138

Equipe Gauguier, "Génomique Fonctionnelle des Phénotypes Complexes"

Escalier F, 2ème étage, Mezzanine,

15, rue de l'Ecole de Médecine

75006, Paris, France

 Tel: 33 (0)1 44 27 71 83                                           Fax: 33 (0)1 44 27 71 62

     E-mail:   fhomodel@orange.fr    

Positions 

 2009-2011: BFA-CNRS EAC 4413 (Director: Pr Jean-Marie Dupret), Paris-Diderot University, Paris 

 2003-2008: CNRS UMR 7059 (Director: Pr A. Ktorza/Bernard Portha), Paris 7 University, Paris 

 2002: INSERM U25 (Director: Pr Jean-François Bach), Necker Hospital, Paris 

 1991-2001: CNRS UMR 8603 (Director: Dr Mireille Dardenne), Necker Hospital, Paris 

 1986-1990: INSERM associate investigator, INSERM U25 (Director: Pr Jean-François Bach), Necker Hospital, Paris 

 1973-1985: Research Associate at INSERM U7 (Director: Pr Philippe Meyer), Necker Hospital, Paris  

Research supports / Travel research grants

• EFSD/MSD grant 2006 
• European Community (5^th PCRD 2000-2002, grant n° QLTR 1999 00276, as a co-coordinator) 
• European Community (BIOMED 1998-2000, grant n° BMH4 CT98 3448) 
• Foundation of France, 1996, 1998 
• ALFEDIAM-LILLY (Prize 1996) 
• Research and Technology Minister (MRT) (1992) 
• INSERM-CONICET travel grants (France-Argentina, 1997-98, 1999-2000, 2005-06) 
• INSERM-CNPq travel grants (France-Brazil, 1997-98, 1999-2000) 
• INSERM-NWO travel grants (France-The Netherlands, 1991-92, 1993-94, 1995-96, 1997-98) 

Editorial board and Journal Reviewer 

·      Reviewer for: Diabetes, Diabetologia  

Membership

·    Past: EASD, ADA, SFD, Endocrine Society, Société des Neurosciences, Société de Neuroendocrinologie Expérimentale

 Field of study 

·   Former research lines  

Contribution to the: 

1) Determination of glucocorticoid receptor number and its relationship with corticosensitivity/resistance in normal rodent lymphoid tissue and in human leukemic cells; 

2) Mechanism of action of glucocorticoids, sex steroids, catecholamines and prostaglandins in lymphocytes; 

3) Measurement of eicosanoid production by cells of the immune and hematopoietic systems and assessment of the effects of anti-inflammatory agents, cytokines and immunomodulatory agents on this production; 

4) Role of prostaglandins in steroidogenesis; 

5) Understanding of the pathophysiology of diabetes in a spontaneous T1D animal model, the nonobese diabetic (NOD) mouse (1990-2003). 

                                                  In the NOD mouse: 

 Ø I  described during the prediabetic stage a transient b-cell hyperactivity that has been confirmed latter in the NOD mouse and also in humans; 

 Ø I  underlined the role of macrophage during normal pancreas development and its disturbances as responsible for the initiation of islet autoimmune reaction; 

 Ø I suggested that peri-islet neuronal cells might be the first targets for the autoimmune response, a hypothesis that has also been developed by a few other groups. 

 In addition to original publications, the data mentioned have been developed in several reviews: 

•  Immunology Today 1996
•   Diabetes and Metabolism 1997a & b 
• Trends in Endocrinology and Metabolism 2002 
• The Institute for Laboratory Animal Research (ILAR) Journal 2004 
•   Discovery Medicine 2004 
• Trends in Immunology 2003 & 2004.

Scientific summary

  Present research line

In October 2003, I moved to Pr Bernard Portha’s laboratory (CNRS UMR 7059, Paris VII University) in order to combine her expertise acquired in the NOD mouse model with the knowledge of the Goto-Kakizaki (GK) rat model acquired by this laboratory. Since that time, I showed that: 

1) An inflammatory process is present in diabetic GK islets in collaboration with Dr Jean-Claude Irminger (Pr Philippe Halban’s laboratory, Geneva, Switzerland) (Diabetes, 2006) and in other spontaneous or induced animal models of T2D as well as in type 2 diabetic patients in collaboration with Dr Marc Donath (Zürich, Switzerland) (Diabetes, 2007); 

2) Islet inflammation is linked to the presence of microangiopathy in diabetic adults (Current Immunology Review 2007; Plos One 2009a); 

3) One-month IL-1 receptor antagonist (IL-1Ra) treatment has a beneficial effect on islet inflammation, vascularization, fibrosis and hyperglycemia (PNAS USA 2009; PloS One 2009a);

4) Neonatal islet microangiopathy is also observed, concomitantly with islet oxidative stress and deficient angiogenesis and elevated circulating cholesterol  and chemokine levels (Plos One 2009b). These data suggest a cholesterol-induced in utero programming of the islet microangiopathy (Diabetologia 2011);

5) Circulating low levels of homocysteine and glutathione are associated with elevated hepatic cystathionine beta-synthase activity from prediabetic stage onwards, probably as a consequence of low or deficient insulin action (BBA 2011); 

6) Increased expression of the regenerating protein REG1 in the exocrine peri-islet area of the pancreas appears to be an adaptive process to islet inflammation in diabetic rats (PloS One 2014). 

      Publications on the GK rat: 

• Homo-Delarche F, Calderari S, Irminger J-C, Rickenbach K, Gangnerau M-N, Coulaud J, Dolz M, Halban P, Portha B, Serradas P. Islet inflammation and fibrosis in a spontaneous model of T2D, the Goto-Kakizaki (GK) rat: potential role of islet microangiopathy. Diabetes 2006, 55: 1625-1633 
• Ehses JA, Perren A, Eppler E, Ribaux P, Pospisilik JA, Maor-Cahn R, Gueripel X, Ellingsgaard H, Schneider MKJ, Biollaz G, Fontana A, Reinecke, M, Homo-Delarche F, Donath, M.Y. Increased number of islet-associated macrophages in type 2 diabetes. Diabetes 2007, 56: 2356-2370 
• Ehses, J.A., Calderari, S., Irminger, J.C., P., Serradas, P., Giroix, M.H., Egli, A., Portha, B., Donath, M.Y., Homo-Delarche, F. Islet inflammation Type 2 Diabetes (T2D): from endothelial to beta-cell dysfunction. Curr. Immunol. Rev. 2007, 3: 216-232 
•  Lacraz G, Giroix M-H, Kassis N, Coulaud J, Galinier A, Noll C, Cornut M, Schmidlin F, Paul, JL, Janel N, Irminger J-C, Kergoat M, Portha B, Donath M, Ehses JA, Homo-Delarche F. Islet endothelial activation and oxidative gene expression is reduced by IL-1Ra treatment in the type 2 diabetic GK rat. PloS One  2009a, 4: e6963 
•  Lacraz G, Figeac F, Movassat J, Kassis N, Coulaud J, Galinier A, Leloup C, Bailbé D, Homo-Delarche F, Portha B. Diabetic β-cells can achieve self-protection against oxidative stress through an adaptive up-regulation of their antioxidative defenses. PloS One 2009b, 4: e6500 
• Ehses JA*, Giroix M-H*, Lacraz G*, Schmidlin F, Coulaud J, Kassis N, Irminger J-C, Kergoat M, Portha B, Homo-Delarche F, Donath MY. IL-1 antagonism reduces hyperglycemia and tissue inflammation in the type 2 diabetic GK rat. PNAS USA 2009, 106: 13998-14003 
• Beauquis J, Homo-Delarche F, Giroix M-H, Ehses JA, Coulaud J, Roig P, Portha B, De Nicola AF, Saravia F. Hippocampal neurovascular and hypothalamic-pituitary-adrenal axis alterations in spontaneously type 2 diabetic GK rats. Exp Neurol, 2010, 222:125-134 
•  Noll C, Lacraz G, Ehses J, Coulaud J, Bailbé D, Paul J-L, Portha B, Homo-Delarche F, Janel N. Early reduction of circulating homocysteine levels in Goto-Kakizaki rat, a spontaneous nonobese model of type 2 diabetes. Biochim Biophys Acta, 2011, 1812:699-702 
• Giroix M-H*, Irminger J-C*, Lacraz G, Noll C, Calderari S, Ehses JA, Coulaud J, Cornut M, Kasssis N, Schmidlin F, Paul J-L, Kergoat M, Janel N, Halban P, Homo-Delarche F. Hypercholesterolemia, signs of islet microangiopathy and altered angiogenesis precede onset of type 2 diabetes in the Goto-Kakizaki (GK) rat. Diabetologia, 2011, 54:2451-2462 
• Calderari S, Irminger J-C, Giroix M-H, Ehses JA, Gangnerau M-N, Coulaud, J, Rickenbach K, Gaugier D, Halban P, Serradas P, Homo-Delarche F. Regenerating 1 and 3b gene expression in the pancreas of type 2 diabetic Goto-Kakizaki (GK) rat. PloS One 2014, 9: e90045