Cécile Denis PhD Haemostasis/Thrombosis
Course and current status
Cécile V. DENIS
Citizenship: French
Professional address: INSERM U. 1176, 80 rue du Général Leclerc, 94276 Le Kremlin-Bicêtre Cedex, tel: 33-1-49-59-56-05
CURRENT POSITION
Director INSERM Unit 1176 (40 people total)
Director of Research at INSERM (Institut National de la Santé et de la Recherche Médicale)
UNIVERSITY DEGREES:
2006 Official habilitation to supervise PhD theses, University Paris 7
1993 PhD in Biological Sciences, University Paris 7
1989 Master in Biological Sciences University Paris 7, Major “Blood cells biology”
1987 Bachelor degree. Major: Cell Biology. University of Rennes I
PROFESSIONAL EXPERIENCE:
Since 2015 INSERM U. 1176 HITh Hemostasis-Inflammation-Thrombosis
2006-2014 INSERM U. 770, “Hémostase et Dynamique Cellulaire Vasculaire”, Kremlin-Bicêtre Hospital
2001-2006 INSERM U. 143, “Hémostase et Biologie Vasculaire”, Kremlin-Bicêtre Hospital (Pr. Dominique Meyer). Research Officer 1st class INSERM. “Avenir 2001” program laureate INSERM
2000-2001 INSERM U. 143. Post-doctoral fellow.
1993-2000 Center for Blood Research, Harvard Medical School, Boston, USA (Pr. Denisa Wagner). Post-doctoral fellow
1988-1993 INSERM U143, “Hémostase et Thrombose”, Kremlin Bicêtre Hospital (Pr. Dominique Meyer and Dr. Dominique Baruch). PhD thesis. Grant recipient from the French Minister for Research and Technology
PRIZES AND AWARDS
Chevalier Légion d’honneur 2012
Recipient of the 18th Biennal ISTH Awards for contribution to Hemostasis (BACH Award from the Internatioal Society of Thrombosis and Hemostasis)
Laureate Prize Bréant, Maujean et Albert 1er de Monaco 2007 of the French Academy of Sciences
Laureate Avenir program from INSERM for young scientists (2001)
Laureate young investigator award French Group for Thrombosis & Haemostasis (GEHT) (1993)
PUBLICATIONS AND PATENTS:
Author of 105 peer-reviewed publications, 1 book chapter and 121 abstracts presented in national and international meetings
10 granted patent applications, 1 under exclusive licence.
30 conferences given at the invitation of organizing committees of national and international meetings
EXPERTISE ACTIVITIES:
Elected member of the scientific council of the Medical Faculty of Paris-Sud (since 2016)
Member of Specialized Scientific Commission n°4 of INSERM (2012-2016)
Member of multinational PhD committees (Netherlands, Germany, Canada, France)
Member of evaluation committees for AERES (French evaluation body for research laboratories)
Member of evaluation committee for ANR (French funding agency)
Member of the Editorial Board of Blood
Reviewer for scientific journals: Blood, Journal of Thrombosis and Haemostasis, PNAS, Arteriosclerosis Thrombosis and Vascular Biology, Plos Pathogens, Plos One, Thrombosis Research
Expertise activities for foreign funding agencies: FWO (Fonds Wetenschappelijk Onderzoek) in Belgium, NHLS (National Health Laboratory Service) Research Trust (South Africa), COFECUB (French-Brazilian projects), Italian Telethon (Italy) and the Landsteiner Foundation for Blood Transfusion (The Netherlands)
Member of the ethical committee CEEA26 for animal experimentation
TEACHING ACTIVITIES:
Teaching participation: Paris 7 Master 2 CVHR “CardioVascular, Hemostasis, Respiration” and Master 1 module “Cell Biology, Microbiology and Therapeutic Innovations” Le Kremlin-Bicêtre Medical School.
Supervision of Master (5) and PhD theses (6)
MEMBERSHIPS
Co-chairman of the Scientific and Standardization committee “Animal Models” of the International Society of Thrombosis & Haemostasis (ISTH) (2012-2015)
Elected member of the board of the French Group for Thrombosis & Haemostasis (GEHT)
Member of the scientific council of AFH (Association Française des Hémophiles)
French Society of Hematology (SFH)
Scientific summary
My research activities are focused on the study of hemostatic proteins and on hemorrhagic disorders such as von Willebrand disease (VWD) and hemophilia.
The two proteins whose deficiency lead to such hemorrhagic syndromes are von Willebrand factor (VWF) and coagulation factor VIII (FVIII). Both proteins circulate in plasma as a complex with VWF strongly influencing the pharmacokinetics of FVIII.
Four major research themes can be distinguished:
1) Study of molecular mechanisms underlying hemostatic/thrombotic processes
Such studies have allowed the identification of new binding partners for VWF. The characterization of these interactions helped us to understand the interplay between VWF and the vascular wall following injury and therefore how VWF can play its role in recruiting blood platelets and in mediating thrombus formation. Development of new biological tools (single domain antibodies derived from llamas) targeting specific VWF functions is currently ongoing and may represent potential anti-thrombotic agents.
2) Development of murine models in hemostasis/thrombosis
VWD is the most common inherited bleeding disorder. A model of severe VWD has been developed during my post-doctoral internship and is used by many laboratories worldwide. This model has allowed us to study VWF structure/function relationships in vivo using hydrodynamic injections. More recently, we have also developed a murine model of a particular subtype of VWD: type 2B VWD. Indeed this subtype is characterized by a thrombocytopenia not observed in any other types or subtypes of VWD. Using our model, we have studied the mechanisms underlying this unusual characteristic and we have also demonstrated the presence of a thrombopathy or altered platelet function. A murine model of thrombotic thrombocytopenic purpura has also been developed in collaboration with another laboratory. All these models are still being studied in our team.
3) Clearance mechanisms of hemostatic proteins
Our team has been pioneer in its studies about the clearance of the VWF/FVIII complex and also about another coagulation protein: factor X. We have identified, the cells, the receptors and the molecular determinants involved in the elimination of these proteins from the circulation. Based on our results, we have designed a long-acting coagulation factors for treatment of hemophilia A. Many studies in this area are being currently carried out.
4) Study of VWF beyond hemostasis
VWF has a complex structure and many binding partners have already been identified. This multiplicity of binding partners lead to VWF being involved in a number of biological processes beyond its classical role in hemostasis. We have been able to demonstrate a direct role of VWF in inflammation but also in tumor cell survival. Currently a collaboration with U1116 in Nancy is ongoing about the role of VWF in smooth muscle cells proliferation.
