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

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