Dr Juergen Roes
Molecular Control of Leukocyte Function and Homeostasis Our research aims to identify genes and cells that are critical in protection from infectious diseases and prevention of immunopathogenesis.
While in vitro studies can provide some insight, identification of the genes and cells that make critical contributions in their physiological context requires direct data from in vivo models. Genome sequencing projects have revealed that more than 99% of the ~20.000 mouse genes have counterparts in humans - a finding which not only endorses the validity of the mouse model, but also explains the similarities in normal physiology and many disease processes. By generating mice deficient in neutrophil proteases or the NADPH oxidase, (a model for human Chronic Granulomatous Disease), we could show that the granule proteases, rather than the reactive 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.
To investigate the function of more widely expressed genes in immunity and inflammation, we are also developing models for cell type specific mutagenesis 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. Our analysis of the TGF-b system in lymphocytes revealed signalling pathways and modulators involved in the physiological control of mucosoal B cell responses and IgA production. By pursuing this approach for use in inflammatory leukocytes, we aim to 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.
Analysis of Immunity and Inflammation in the Mouse Model
Contributions to BSc in Immunology MSc in Molecular Medicine
Dr Andrew Williams
- Lucas T, Waisman A, Ranjan R, Roes J, Krieg T, Muller W, Roers A, Eming SA (2010). Differential roles of macrophages in diverse phases of skin repair. J Immunol, 184(7), 3964 - 3977.
- Nishimura EK, Suzuki M, Igras V, Du J, Lonning S, Miyachi Y, Roes J, Beermann F, Fisher DE (2010). Key roles for transforming growth factor beta in melanocyte stem cell maintenance. Cell Stem Cell, 6(2), 130 - 140. doi:10.1016/j.stem.2009.12.010
- Hauri-Hohl MM, Zuklys S, Keller MP, Jeker LT, Barthlott T, Moon AM, Roes J, Hollander GA (2008). TGF-beta signaling in thymic epithelial cells regulates thymic involution and postirradiation reconstitution. Blood, 112, 626 - 634. doi:10.1182/blood-2007-10-115618
- Lacy-Hulbert A, Smith AM, Tissire H, Barry M, Crowley D, Bronson RT, Roes JT, Savill JS, Hynes RQ (2007). Ulcerative colitis and autoimmunity induced by loss of myeloid alphav integrins. Proceedings of the National Academy of Sciences of the United States of America, 104(40), 15823 - 15828.
- Chua F, Dunsmore SE, Clingen PH, Mutsaers SE, Shapiro SD, Segal AW, Roes J, Laurent GJ (2007). Mice lacking neutrophil elastase are resistant to bleomycin-induced pulmonary fibrosis. American Journal of Pathology, 170(1), 65 - 74. doi:10.2353/ajpath.2007.060352
- Roes J (2007). Conditional mutagenesis reveals immunological functions of widely expressed genes: activation thresholds, homeostatic mechanisms and disease models. Handbook of Experimental Pharmacology, 178, 289 - 314.
- D Antonio M, Droggiti A, Feltri ML, Roes J, Wrabetz L, Mirsky R, Jessen KR (2006). TGFß type II receptor signaling controls Schwann cell death and proliferation in developing nerves. Journal of Neuroscience, 26(33), 8417 - 8427. doi:10.1523/JNEUROSCI.1578-06.2006
- McCarty JH, Lacy-Hulbert A, Charst A, Bronson RT, Crowley D, Housman D, Saville J, Roes J, Hynes RO (2005). Selective ablation of alphav integrins in the central nervous system leads to cerebral hemorrhage, seizures, axonal degeneration and premature death. Development, 132(1), 165 - 176.
- Lacy-Hulbert A, McCarty J, Savill JS, Roes JT, Hynes RO (2005). Conditional deletion of alpha (v) integrins causes inflammatory bowel disease..
- Mitchison NA, Harbord M, Hankin A, Roes J (2005). Conditional haploinsufficiency of NCF1 (encoding p47 (phox), a signalling gene with a heterozygous phenotype potentially subject to natural selection. Immunology Letters, 97, 63 - 67.
- Thomas RM, Schmedt C, Novelli M, Choi BK, Skok J, Tarakhovsky A, Roes J (2004). C-terminal SRC kinase controls acute inflammation and granulocyte adhesion. Immunity, 20(2), 181 - 191. doi:10.1016/s1074-7613(04)00023-8
- Borsutzky S, Cazac BB, Roes J, Guzman CA (2004). TGF-beta receptor signalling is critical for mucosal IgA responses. The Journal of Immunology, 173(5), 3305 - 3309.
- Roes J, Choi BK, Cazac BB (2003). Redirection of B cell responsiveness by transforming growth factor beta receptor. Proceedings of the National Academy of Sciences of the United States of America, 100(12), 7241 - 7246. doi:10.1073/pnas.0731875100
- Roes J, Choi BK, Power D, Xu P, Segal AW (2003). Granulocyte function in grancalcin-deficient mice. Molecular and Cellular Biology, 23(3), 826 - 830. doi:10.1128/MCB.23.3.826-830.2003
- Messina CG, Reeves EP, Roes J, Segal AW (2002). Catalase negative Staphylococcus aureus retain virulence in mouse model of chronic granulomatous disease. FEBS Letters, 518(1-3), 107 - 110.
- Mitchison NA, Roes JT (2002). Patterned variation in murine MHC promoters. Proceedings of the National Academy of Sciences of the United States of America, 99(16), 10561 - 10566. doi:10.1073/pnas.152329999
- Roes J (2001). Targeted Mutagenesis in the Immune System. In (Ed.), Encyclopedia of Life Sciences (pp. - ). : Macmillan Reference Ltd.
- Lacy-Hulbert A, Thomas R, Li XP, Lilley CE, Coffin RS, Roes J (2001). Interruption of coding sequences by heterologous introns can enhance the functional expression of recombinant genes. Gene Therapy, 8(8), 649 - 653.