Dr Mark Travis

Mark Travis – Research Summary

Dr Mark Travis

Dr Mark Travis

Our immune system has evolved to protect the body from harmful pathogens. Immune responses must be tightly regulated to allow rapid initiation of an immune response upon infection, and to quickly resolve the response when the pathogen has been eliminated to prevent tissue damage. In addition, the immune system must be kept in a resting state in normal situations to prevent harmful responses against self-tissues, leading to autoimmune disease. Work in my laboratory aims to to determine important cellular and molecular pathways that prevent self-harmful immune responses (resulting in autoimmune disease), and how such pathways are involved in active responses to infection.

Our current work focuses on how the important cytokine transforming growth factor-beta (TGF-beta) regulates immunity. We have identified an important pathway by which antigen-presenting dendritic cells activate TGF-beta (via an integrin receptor called alphavbeta8), and have shown that this pathway is critical in controlling T-cell responses and preventing autoimmunity. Current studies aim to identify the role of this TGF-beta pathway in different types of dendritic cell present in different tissues of the body, and also the importance in active immune responses to bacterial and parasitic infections. Such work will help us better understand the molecular mechanisms that balance immune tolerance at times of health with the need for robust responses upon infection, therefore identifying potential therapeutic targets for disease of the immune system.

The Travis lab is a member of the Manchester Immunology Group, the Wellcome Trust Centre for Cell-Matrix Research and the Manchester Collaborative Centre for Inflammation Research.

Email:
Mark.Travis-2@manchester.ac.uk Tel: 0161 275 1701


People

Mark Travis – People

Abdulelah Aljuaid (Saudi Arabian government-funded PhD student)
Josh Casulli (Dstl-funded PhD student)
Joshua Dow
Stephanie Houston (MRC-funded Post-Doctoral Fellow)
Aoife Kelly (MCCIR-funded Post-Doctoral Fellow)
Stefano Rossi
Ellie Sherwood (MRC-funded PhD student)
Ellie Shuttleworth (MCCIR-funded Clinical Fellow)
Catherine Smedley (MRC-funded Technician)

Past members

Tom Fenton (BBSRC DRINC-funded PhD student)
Felipe Melo Gonzalez (Chilean government-funded PhD student)
Kevin Rich (BBSRC-funded PhD student)
Asia Klementowicz (2008-2011, BBSRC-funded PhD student)
Simon Vautier (2013-2014, Dstl-funded Post-Doctoral Fellow)
John Worthington (2008-2014, MRC-funded Post-Doctoral Research Associate)


People

Mark Travis – People

Abdulelah Aljuaid (Saudi Arabian government-funded PhD student)
Josh Casulli (Dstl-funded PhD student)
Joshua Dow
Stephanie Houston (MRC-funded Post-Doctoral Fellow)
Aoife Kelly (MCCIR-funded Post-Doctoral Fellow)
Stefano Rossi
Ellie Sherwood (MRC-funded PhD student)
Ellie Shuttleworth (MCCIR-funded Clinical Fellow)
Catherine Smedley (MRC-funded Technician)

Past members

Tom Fenton (BBSRC DRINC-funded PhD student)
Felipe Melo Gonzalez (Chilean government-funded PhD student)
Kevin Rich (BBSRC-funded PhD student)
Asia Klementowicz (2008-2011, BBSRC-funded PhD student)
Simon Vautier (2013-2014, Dstl-funded Post-Doctoral Fellow)
John Worthington (2008-2014, MRC-funded Post-Doctoral Research Associate)


Collaborators

Steve Anderton, University of Edinburgh
Riccardo D'Elia, Defence Science and Technology Laboratory (Dstl)
Graeme Clark, Defence Science and Technology Laboratory (Dstl)
Scott Levison (Central Manchester University Hospitals NHS Foundation Trust)
Julien Marie (University of Lyon)

Biography

I am a Senior Lecturer based in the Manchester Immunology Group, Manchester Collaborative Centre for Inflammation Research, and the Wellcome Trust Centre for Cell-Matrix Research.

I received a first class honours degree in Biochemistry and Genetics from Lancaster University in 2000, and completed a PhD in protein biochemistry at the University of Manchester in 2004, studying the structure and function of integrin adhesion receptors. I then went to the University of California, San Francisco, as an American Lung Association Fellow, where I worked on the role of integrins and TGF-β in regulating immune response. I returned to Manchester as a Royal Commission Fellow in late 2006, before taking up his position as an RCUK Fellow in October 2007 and becoming a lecturer in 2012.

Publications

  • Fenton TM, Kelly A, Shuttleworth EE, Smedley C, Atakilit A, Powrie F, Campbell S, Nishimura SL, Sheppard D, Levison S, Worthington JJ, Lehtinen MJ, Travis MA (2016). Inflammatory cues enhance TGFβ activation by distinct subsets of human intestinal dendritic cells via integrin αvβ8. Mucosal Immunol. doi: 10.1038/mi.2016.94.
  • Ucar O, Li K, Dvornikov D, Kreutz C, Timmer J, Matt S, Brenner L, Smedley C, Travis MA, Hofmann TG, Klingmüller U, Kyewski B (2016). A Thymic Epithelial Stem Cell Pool Persists throughout Ontogeny and Is Modulated by TGF-β. Cell Rep. 17:448-457.
  • Luda KM, Joeris T, Persson EK, Rivollier A, Demiri M, Sitnik KM, Pool L, Holm JB, Melo-Gonzalez F, Richter L, Lambrecht BN, Kristiansen K, Travis MA, Svensson-Frej, M, Kotarsky, K, Agace, WW (2016). IRF8 Transcription-Factor-Dependent Classical Dendritic Cells Are Essential for Intestinal T Cell Homeostasis. Immunity. 44, 4, p. 860-874
  • Worthington JJ, Kelly A, Smedley C, Bauché D, Campbell S, Marie JC, Travis MA (2015). Integrin αvβ8-Mediated TGF-β Activation by Effector Regulatory T Cells Is Essential for Suppression of T-Cell-Mediated Inflammation. Immunity. 2015 May 19;42(5):903-15
  • Travis MA & Sheppard D (2014). TGF-ß activation and function in immunity. Ann. Rev. Immunol., v. 32, pg 51-82
  • Liu W, Zi M, Tsui H, Chowdhury SK, Zeef L, Meng QJ, Travis M, Prehar S, Berry A, Hanley NA, Neyses L, Xiao RP, Oceandy D, Ke Y, Solaro RJ, Cartwright EJ, Lei M, Wang X (2013). A novel immunomodulator, FTY-720 reverses existing cardiac hypertrophy and fibrosis from pressure overload by targeting NFAT (nuclear factor of activated T-cells) signaling and periostin. Circ Heart Fail., 6, 833-44
  • Worthington JJ, Klementowicz JE, Rahman S, Czajkowska BI, Smedley C, Waldmann H, Sparwasser T, Grencis RK, Travis MA (2013). Loss of the TGFß-Activating Integrin avß8 on Dendritic Cells Protects Mice from Chronic Intestinal Parasitic Infection via Control of Type 2 Immunity. PLoS Pathog, 9, e1003675.
  • Worthington JJ, Fenton TM, Czajkowska BI, Klementowicz JE, Travis MA (2012). TGFß activation by dendritic cells: a crucial pathway during immune homoeostasis and inflammation. Immunobiology, 217, 1259-65.
  • Klementowicz JE, Travis MA, Grencis RK (2012). Trichuris muris: a model of gastrointestinal parasite infection. Semin Immunopathol, 34, 815-28.
  • Kimber I, Travis MA, Martin SF, Dearman RJ (2012). Immunoregulation of skin sensitization and regulatory T cells. Contact Dermatitis, 2012 Jul 14. doi: 10.1111/j.1600-0536.2012.02148.x
  • Giacomini MM, Travis, MA, Kudo K, Sheppard D (2012). Epithelial cells utilize cortical actin/myosin to activate latent TGF-beta through integrin alphav beta6-dependent physical force. Exp. Cell Res., 318, 716-22.
  • Worthington JJ, Czajkowska B, Melton AC, Travis MA (2011). Intestinal Dendritic Cells Specialize To Activate Transforming Growth Factor-ß and Induce Foxp3+ T Regulatory Cells via integrin avß8. Gastroenterology, 141, 1802-12.
  • Ilic N, Worthington JJ, Gruden-Movsesijan A, Travis MA, Sofronic-Milosavljevic L, Grencis RK (2011) Antigens from different life stages of the helminth Trichinella spiralis prime a mixed Th1/Th2 immune response but do not induce de novo generation of Foxp3+ T cells in vitro. Parasite Immunology, 33, 572-82.
  • Worthington JJ, Klementowicz JE, Travis MA (2011). TGFβ: a sleeping giant awoken by integrins. Trends in Biochem. Sci. 36, 47-54.
  • Melton AC, Bailey-Bucktrout SL, Travis MA, Fife BT, Bluestone JA, Sheppard D (2010). αvß8 integrin on dendritic cells regulates Th17 cell development and experimental autoimmune encephalomyelitis in mice. J. Clin Invest, 120, 4436-44.
  • Travis MA, Reizis B, Melton AC, Masteller E, Tang Q, Proctor JM, Wang Y, Bernsetin X, Huang X, Reichardt LF, Bluestone JA, Sheppard D (2007). Loss of integrin αvβ8 on dendritic cells causes autoimmunity and colitis in mice. Nature, 449, 361-65