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Dr Jürgen Roes
Jurgen
Roes Juergen Roes Jurgen Roes
Juergen Roes
Profile
Since Oct 2003 Reader ("Assoc. Prof.") in Molecular
Immunology
2001 - Deptartment of Immunology and Molecular Pathology, UCL
1996 - Wellcome Senior Research Fellow in Basic Biomedical Sciences,
Deptartment of Medicine, UCL
1994 - Research Fellow, Dept. Medicine, UCL
1993 - PhD (Dr rer nat) in Genetics/Immunology, University of Cologne,
FRG
1988 - Degree (Dipl) in Biology/Genetics, University of Cologne, FRG
Research Themes
Molecular Control
of Leukocyte Function and Homeostasis
Our main research focus is the inflammatory response, its effector
mechanisms and its regulation. Normally preventing infections by
killing microbial pathogens, inflammatory leukocytes can also drive
pathogenesis and tissue destruction in autoimmune inflammatory
diseases, which may affect virtually any organ and are common in the
form of rheumatoid arthritis or potentially fatal in septic shock.
We employ the mouse as a model, to test gene
function in vivo by means of gene targeted mutants, generated through
homologous recombination in embryonic stem cells. Genome sequencing
projects have revealed that more than 99% of the ~27.000 mouse genes
have functional counterparts in humans - a finding which not only
endorses the mouse as a valid model, but also explains the similarities
in normal physiology and many disease
processes.
By generating mice deficient in Elastase (Ela2) and Cathepsin G (Ctsg)
or the NADPH oxidase, (a model for human Chronic Granulomatous
Disease), we could show that the granule proteases, rather than
chemicals produced by the NADPH oxidase, are the critical effectors in
microbial killing and immunopathogenesis. This finding prompted a
re-evaluation of the anti-microbial effector mechanism of neutrophils.
Role of widely expressed
genes in leukocyte function and immune regulation
Conditional mutagenesis (Cre/loxP)
The expression of many genes with key regulatory functions is not
restricted to cells of the immune system. Germline inactivation likely
causes lethality or major distortions in multiple cell types hence
precluding the analysis of leukocyte-specific functions. To avoid this,
we develop mouse models with cell type restricted mutations of widely
expressed genes. This approach is based on the Cre/loxP
system.
Based on this approach we identified the inhibitory tyrosine kinase csk
as a key regulator of inflammatory cell recruitment and revealed
signalling pathways and modulators mediating the TGF-beta induced
redirection of B cell responsiveness for effective mucosal immunity
through production of IgA.
By applying this approach for use in inflammatory leukocytes, we will
gain further insight into the regulatory requirements for controlled
inflammatory responses in vivo. The molecular pathways and mediators
identified may facilitate novel therapeutic approaches aiming to
suppress pathogenic inflammation or to enhance resistance to infectious
diseases.
Selected
Publications
Thomas
RM, Schmedt C, Novelli M, Choi BK, Skok J, Tarakhovsky A, Roes J.
C-terminal SRC kinase controls acute inflammation and granulocyte
adhesion.
Immunity. 2004 Feb;20(2):181-91.
Roes
J, Choi BK, Cazac BB.
Redirection of B cell responsiveness by transforming growth factor
{beta} receptor.
Proc Natl Acad Sci U S A. 2003 Jun
10;100(12):7241-6.
Epub 2003 May 28.
Reeves
EP, Lu H, Jacobs HL, Messina CG, Bolsover S, Gabella G, Potma EO,
Warley A, Roes J, Segal AW.
Killing activity of neutrophils is mediated through activation of
proteases by K+ flux.
Nature. 2002 Mar 21;416(6878):291-7.
Cazac
BB, Roes J.
TGF-beta Receptor Controls B Cell Responsiveness and Induction of IgA
In Vivo.
Immunity. 2000 Oct 1;13(4):443-451.
Tkalcevic
J, Novelli M, Phylactides M, Iredale JP, Segal AW, Roes J.
Impaired immunity and enhanced resistance to endotoxin in the absence
of neutrophil elastase and cathepsin G.
Immunity. 2000 Feb;12(2):201-10.
Reviews and Book Chapters
J. Roes
Conditional Mutagenesis Reveals Immunological Functions of Widely
Expressed Genes: Activation Thresholds,
HomeostaticMechanismsandDiseaseModels p289
in Conditional
Mutagenesis: An Approach to Disease Models
Series : Handbook of Experimental Pharmacology , Vol. 178
Feil, Robert; Metzger, Daniel (Eds.)
2007, XI, 500 p.,
ISBN-10: 3-540-35108-6
ISBN-13: 978-3-540-35108-5
Links
Roes-J
Publications (pubmed)
(Keywords:
immunity, inflammation, TGF-beta, TGF, TGF-beta, TGF-{beta}, csk,
elastase, cathepsin G, conditonal mutagenesis, Cre/loxP, microarrays,
mutant)
This page last modified
15 June 2007
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Dr Jürgen Roes
Reader in Molecular Immunology
Department of Immunology & Molecular Pathology
Windeyer Building
46 Cleveland Street
London W1T 4JF
Tel:
Staff directory
Email: Jürgen Roes
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