Translational Research - Université de Genève

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