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Franco-Brazilian Collaboration in Hematology International Research Network on Hematology (IRNH)

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Franco-Brazilian Collaboration in Hematology International Research Network on Hematology (IRNH) Franco-Brazilian collaboration in Hematology International Research Network on Hematology (IRNH) New emerging collaboration The genesis of a project: from the late 90s Analysis of the 677C→T mutation of the Methylenetetrahydrofolate Reductase Gene in Different Ethnic Groups R. F. Franco, A. G. Araújo, J. F. Guerreiro, J. Elion, M. A. Zago Thromb Haemost. 1998 Jan;79(1):119-21. The phylogeography of mitochondrial DNA haplogroup L3g in Africa and the Atlantic slave trade. Bortoloni MC, Da Silva WA Jr, Zago MA, Elion J, Krishnamoorthy R, Goncalves VF, Pena SD Am. J. Hum. Genet. 75:523–524, 2004 from population genetics… ….to cellular and molecular hematology Cellular and Molecular Effects of Hydroxycarbamide in Sickle Cell Patients Silva-Pinto AC, de Cássia Viu Carrara R, V.B. Palma P, Zago MA, Elion J, Covas DT Current Pharmacogenomics and Personalized Medicine, 2014, 12, 114-122 15 publications 1998-2015 The genesis of a project (II): from the early 2000s clinical hematology Host defense and inflammatory gene polymorphisms are associated with outcomes after HLA-identical sibling bone marrow transplantation Vanderson Rocha, Rendrik F. Franco, Raphael Porcher, Henrique Bittencourt, Wilson A. Silva Jr, Aurelien Latouche, Agnes Devergie, Helene Esperou, Patricia Ribaud, Gerard Socie, Marco Antonio Zago, and Eliane Gluckman Blood. 2002 Dec 1;100(12):3908-18 Age-adjusted recipient pretransplantation telomere length and treatment-related mortality after hematopoietic stem cell transplantation. Peffault de Latour R, Calado RT, Busson M, Abrams J, Adoui N, Robin M, Larghero J, Dhedin N, Xhaard A, Clave E, Charron D, Toubert A, Loiseau P, Socié G, Young NS. Blood. 2012;120(16):3353-9 7 publications 2002-2015 The genesis of a project (III): 2013 USP-Paris-Diderot Symposium on Hematology and Immunology July 2015 2016-2019 Initial purpose The purpose of the “International research network on Hematology” (INRH) is to facilitate collaborations around the following topic: Basic and translational research on non-malignant hematological diseases: - sickle cell anemia - aplastic anemia - autoimmune diseases Actions - integrate activities from different fields: hematology, biochemistry, genetics, genomics, cell biology, immunology, cell therapy, clinical research and allied health sciences - search for funding - exchange of researchers and students, - organization of training courses and scientific meetings - development of training tools Coordination and Partners French scientific coordinators Eliane Gluckman Laboratoire Eurocord EA4412 IUH Paris Diderot - USPC Jacques Elion UMR_S 1134 Inserm Paris Diderot - USPC Brazilian scientific coordinators Rodrigo T. Calado Faculdade de Medicina de Ribeirão Preto FMRP-USP Belinda P. Simões Faculdade de Medicina de Ribeirão Preto FMRP-USP Partners UMR_S 1134 Inserm Paris Diderot Caroline Le Van Kim, Wassim El Nemer, Jacques Elion UMR_S1134I UH Inserm Paris Diderot Antoine Toubert EA4412 IUH Paris Diderot Eliane Gluckman, Régis Peffault de la Tour UMR_S1163 Imagine Inserm Paris Descartes Olivier Hermine, Marina Cavazzana Hemocentro FMRP CTC Rodrigo Calado, Belinda Simoes, Dimas Covas, Simone Kashima-Haddad Network themes Three major themes: - sickle cell anemia - aplastic anemia - autoimmune diseases Present SCD geographic distribution Healthy carriers ≈ 5% of the world population 300.000 newborns/year (80% in low income countries) Present SCD geographic distribution clearly SCD is a global issue SCD incidence Global 1/2,700 Parisian area 1/1,050 SCD incidence 1/300 Sickle Cell Disease 10/15,000 patients in Mainland France 2,500 patients in ovesea territories Réunion & Mayote Islands population 1 million France: a country with overseas territories Integrated Red Blood Cell Biology Paris UMR_S1134 Guadeloupe CAribbean network of REsearchers on Pointe-à-Pitre Sickle cell disease and Thalassemia Réunion Sickle Cell Disease in Brazil MA 1:1400 PE 1:1400 BA 1:650 GO 1:1400 Number of births: 3 millions (2012) MG 1:1400 MS 1:8300 ES 1:1800 SP 1:4000 New SCD cases: 2.5 - 3,000 RJ 1:1200 PR e Mean incidence : 1/1000 SC 1:13000 RS 1:13500 HbS: a single mutation but a polysystemic disease p.Val6Glu → HbS free Hb NO deoxyHbS twopolymerisation trigerring scavenging factors Haemolysis Abnormal adhesion to endothelial cells Vasoocclusion Acute complications - painful crises - dactilytis Steinberg M.H., 1999 - acute chest syndrome Inserm U1134U1134 HbS: a single mutation but a polysystemic disease p.Val6Glu → HbS Polysystemic chronic complications free Hb NO deoxyHbS twopolymerisation trigerring scavenging Nonhemorrhagic Pulmonary factors Stroke Hypertension HaemolysisHaemolysis Renal Cholelithiasis Failure Abnormal adhesion to endothelial cells Priapism Osteonecrosis VasoocclusionVasoocclusion Acute complications Leg (VOC) Bacteremia- painful crises Ulceration - dactilytis Steinberg M.H., 1999 - acute chest syndrome - splenic sequestration Inserm U1134U1134 Vasoocclusion: a complex mechanism a cascade of interactions between RBC, neutrophils, platelets and activated endothelium - inflammation intravital microscopy (mouse) RBC (blue), neutrophils (red) adapted from Frenette et al, 2016 The IRNH Work program on SCD I Basic and translational research Jacques Elion and Dimas Covas WP1: Search for modifying genes WP2: Adenosine signaling and pathophysiology of priapism WP3: Innovative approaches for novel biomarkers and anti- adhesive therapies II Clinical research Eliane Gluckman and Belinda P. Simões WP1: Outcome of hematopoietic stem cell transplantation for SCD WP2: Elaboration of transplant protocols with alternative donors WP3: Endothelial damage in SCD WP4: HLA and other genetic polymorphisms in sickle cell disease WP5: Immunological reconstitution after HSCT The IRNH Work program on SCD I Basic and translational research Jacques Elion and Dimas Covas WP1: Search for modifying genes WP2: Adenosine signaling and pathophysiology of priapism WP3: Innovative approaches for novel biomarkers and anti- adhesive therapies II Clinical research Eliane Gluckman and Belinda P. Simões WP1: Outcome of hematopoietic stem cell transplantation for SCD WP2: Elaboration of transplant protocols with alternative donors WP3: Endothelial damage in SCD WP4: HLA and other genetic polymorphisms in sickle cell disease WP5: Immunological reconstitution after HSCT Combined variants • Cell-to-Cell Signalling and Interaction; • Hematological System Development and Function; • Immune Cell Trafficking. • Cardiac Arrythmia, Cardiovascular Disease; • Cell Morphology. Histamine Biosynhesis IL-10 Signaling Toll-like Receptor Signaling Arsenate Detoxification I (Glutaredoxin) PPAR Signaling Creatine-phosphate Biosynthesis IL-6 Signaling Aryl Hydrocarbon Receptor Signaling Tec Kinase Signaling NF-kB Signaling Differential Regulation of Cytokine Production in Intestinal Ephitelial Cells by IL-17A and IL-17F The IRNH Work program on SCD I Basic and translational research Jacques Elion and Dimas Covas WP1: Search for modifying genes WP2: Adenosine signaling and pathophysiology of priapism WP3: Innovative approaches for novel biomarkers and anti- adhesive therapies II Clinical research Eliane Gluckman and Belinda P. Simões WP1: Outcome of hematopoietic stem cell transplantation for SCD WP2: Elaboration of transplant protocols with alternative donors WP3: Endothelial damage in SCD WP4: HLA and other genetic polymorphisms in sickle cell disease WP5: Immunological reconstitution after HSCT The IRNH Work program on SCD I Basic and translational research Jacques Elion and Dimas Covas WP1: Search for modifying genes WP2: Adenosine signaling and pathophysiology of priapism WP3: Innovative approaches for novel biomarkers and anti- adhesive therapies II Clinical research Sickle cell disease: an international Elianesurvey of Gluckman results of HLA-identical and Belinda sibling P. hematopoietic Simões WP1:stem cell Outcome transplantation. of hematopoietic stem cell transplantation for SCD Gluckman E1,2, Cappelli B2, Bernaudin F3, Labopin M4, Volt F1,2, Carreras J5, Pinto Simões B6, Ferster A7, Dupont S8, de la WP2:Fuente J9 ,ElaborationDalle JH10, Zecca M11 of, Walters transplant MC12, Krishnamurti protocols L13, Bhatia withM14, Leung alternative K15, Yanik G16, Kurtzberg donors J17, Dhedin N18, Kuentz M3, Michel G19, Apperley J20, Lutz P21, Neven B22, Bertrand Y23, Vannier JP24, Ayas M25, Cavazzana WP3:M26,27,28, Matthes-MartinEndothelial S29, Rochadamage V1,30,31, Elayoubi in SCD H1,2, Kenzey C1,2, Bader P32, Locatelli F33,34, Ruggeri A1,2,35, Eapen M5; Eurocord, the Pediatric Working Party of the European Society for Blood and Marrow Transplantation, and the WP4:Center for HLA International and Blood other and Marrowgenetic Transplant polymorphisms Research. in sickle cell disease WP5:Blood. 2017 Immunological Mar 16;129(11):1548-1556. reconstitution after HSCT Actions - integrate activities from different fields: hematology, biochemistry, genetics, genomics, cell biology, immunology, cell therapy, clinical research and allied health sciences - search for funding - exchange of researchers and students, - organization of training courses and scientific meetings - development of training tools Actions - integrate activities from different fields: hematology, biochemistry, genetics, genomics, cell biology, immunology, cell therapy, clinical research and allied health sciences - search for funding COFECUB-CAPES COFECUB-USP Idex Brésil USPC Actions - integrate activities from different fields: hematology, biochemistry, genetics, genomics, cell biology, immunology,
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