Translational Research - Université de Genève
Translational Research - Université de Genève
Translational Research - Université de Genève
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Host Response<br />
Karl-Heinz Krause<br />
Department of Pathology and Immunology<br />
Karl-Heinz Krause obtained his medical <strong>de</strong>gree in 1984 at the University of Munich, where he<br />
also trained in internal medicine. After Fellowships at the Geneva University Hospitals (1984-<br />
87) and the University of Iowa Hospitals, USA (1987-89), he was recruited as a junior faculty<br />
member in Geneva. He was appointed Associate Professor in 1998 and full Professor in 2001 at<br />
the Department of Internal me<strong>de</strong>cine and Geriatrics. Since 2005 he has been affiliated to the<br />
Department of Pathology and Immunology, as well as the Department of Genetic and<br />
Laboratory Medicine , HUG.<br />
NADPH oxidases<br />
Reactive oxygen species (ROS) are a doubled-edged sword. They have crucial physiological<br />
functions, from host <strong>de</strong>fence to participation in biosynthetic processes and from intracellular<br />
signaling to regulation of gene expression. However, they can also be <strong>de</strong>structive and are linked<br />
to many disease processes. The NOX family of NADPH oxidases are one of the major sources<br />
of ROS and our laboratory is particularly interested in this enzyme family. ROS-generating NOX<br />
enzymes are a phylogenetically ancient system found in many unicellular organisms. They have<br />
a range of complex functions in multicellular organisms, notably a role in host <strong>de</strong>fence and<br />
inflammation. Much has been learned from patients with chronic granulomatous diseases<br />
(genetic NOX2 <strong>de</strong>ficiency), diseases characterised by the concommitant occurence of immune<br />
<strong>de</strong>ficiency and hyperinflammation.<br />
Neural differentiation of pluripotent stem cells<br />
A second focus of our laboratory is neuronal differentiation of pluripotent stem cells. Such<br />
differentiation protocols can be used to generate in vitro human neural cells and tissues. This<br />
is particularly relevant for the creation of human mo<strong>de</strong>l systems for diseases of the central<br />
nervous system. Among others, we are using the system to study viral infection of the human<br />
CNS. Also, we are working on the response to tumour invasion of human neural tissues, which<br />
in many respects can mimic antiviral responses.<br />
64 <strong>Université</strong> <strong>de</strong> <strong>Genève</strong> • Faculté <strong>de</strong> mé<strong>de</strong>cine<br />
Sorce S, Schiavone S, Tucci P, Colaianna M, Jaquet V, Cuomo V, Dubois-Dauphin M, Trabace L,<br />
and Krause KH (2010) The NADPH oxidase NOX2 controls glutamate release: a novel<br />
mechanism involved in psychosis-like ketamine responses. J Neurosci. 30:11317-25.<br />
Li B, Bedard K, Sorce S, Hinz B, Dubois-Dauphin M, Krause KH (2009) NOX4 expression in human<br />
microglia leads to constitutive generation of reactive oxygen species and to constitutive<br />
IL-6 expression. Journal of Innate Immunity 1:570-581.<br />
Bedard K, Attar H, Bonnefont J, Jaquet V, Borel C, Plastre O, Stasia MJ, Antonarakis SE, Krause<br />
KH (2009) Three common polymorphisms in the CYBA gene form a haplotype associated<br />
with <strong>de</strong>creased ROS generation. Hum Mutat 30:1123-33.<br />
Schäppi M, Deffert C, Fiette L, Gavazzi G, Herrmann F, Belli D, Krause KH (2008) Branched fungal<br />
beta-glucan causes hyperinflammation and necrosis in phagocyte NADPH oxidase<strong>de</strong>ficient<br />
mice. J Pathol. 214:434-44.<br />
Bedard K, Krause KH (2007) The NOX family of ROS-generating NADPH oxidases: physiology<br />
and pathophysiology. Physiol Reviews 87(1):245-313.<br />
Contact: Karl-Heinz.Krause@unige.ch<br />
Host Response<br />
<strong>Université</strong> <strong>de</strong> <strong>Genève</strong> • Faculté <strong>de</strong> mé<strong>de</strong>cine<br />
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