Brice KORKMAZ PhD Researcher - INSERM
Course and current status
-10/2009 – : INSERM CR1 Position
INSERM U-618 « Protéases et Vectorisations pulmonaires »
Tours-France
Research work: Targeting neutrophil elastase, proteinase 3 and cathepsin G in lung diseases
-02/2007 – 10/2009 : Post-doctoral position (Granted by Alexander von Humboldt
Foundation and German Research Council),
Max-Planck Institute Department of Neurobiology, Department of Neuroimmunology, Martinsried, Munich, Germany
Supervisor: Dr Dieter E. JENNE
Research work: Proteinase 3 in Wegener granulomatosis
-02/2006 - 02/2007 : Post-doctoral position (Granted by National Institute of Health),
University of Washington, Div. Medical Genetics, Dept. Medicine, Seattle, WA, USA
Supervisor: Dr Marshall S. HORWITZ
Research work: Neutrophil elastase in hereditary human neutopenias
-2005-2006 : Post-doctoral position (Granted by Vaincre La Mucoviscidose)
« Protéases et Vectorisation pulmonaires »
INSERM U-618 (Institut National de la Santé et de la Recherche Médicale)
Supervisor: Dr Francis GAUTHIER
Research work: Neutrophil elastase, proteinase 3 and cathepsin G in chronic lung inflammatory diseases
-2001-2004 : Ph.D thesis, University of François Rabelais (Tours, France)
Title: Enzymatic characterization of serine proteinases from human neutrophil azurophil granules
Supervisor: Dr Francis GAUTHIER
INSERM U-618 « Protéases et Vectorisations pulmonaires »
-2000-2001 : Master degree at the University of François Rabelais (Tours, France)
Specialization in Enzymology, Molecular Biology, Immunology, Microbiology
Title: Role of Cathepsine G in inflammatory pulmonary diseases: design of new fluorogenic substrate
Supervisor: Dr Francis GAUTHIER
INSERM EMI 0010 “Laboratoire d’Enzymologie et Chimie des Protéines”
Scientific summary
Dr Brice Korkmaz' s scientific interests focus on physiopathological functions of neutrophil serine proteinases. Polymorphonuclear neutrophils are the first cells recruited to inflammatory sites and form the earliest line of defense against invading microorganisms. Neutrophil elastase, proteinase 3, and cathepsin G are three hematopoietic serine proteases stored in large quantities in neutrophil cytoplasmic azurophilic granules. They act in combination with reactive oxygen species to help degrade engulfed microorganisms inside phagolysosomes. These proteases are also externalized in an active form during neutrophil activation at inflammatory sites, thus contributing to the regulation of inflammatory and immune responses. As multifunctional proteases, they also play a regulatory role in noninfectious inflammatory diseases. Mutations in the ELA2/ELANE gene, encoding neutrophil elastase, are the cause of human congenital neutropenia. Neutrophil membrane-bound proteinase 3 serves as an autoantigen in Wegener granulomatosis, a systemic autoimmune vasculitis. All three proteases are affected by mutations of the gene (CTSC) encoding dipeptidyl peptidase I, a protease required for activation of their proform before storage in cytoplasmic granules. Mutations of CTSC cause Papillon-Lefe`vre syndrome. Because of their roles in host defense and disease, elastase, proteinase 3, and cathepsin G are of interest as potential therapeutic targets. Dr B. Korkmaz and its collaborators are studying the physicochemical functions of these proteases, toward a goal of better delineating their role in human diseases and identifying new therapeutic strategies based on the modulation of their bioavailability and activity. (Reviewed in Korkmaz et al., 2010, Pharmacological Reviews)
