Professor Marion MacFarlane

  • Deputy Director
  • MRC Investigator
Professor Marion MacFarlane

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About

Marion MacFarlane is Deputy Director of the MRC Toxicology Unit and Programme lead for the Molecular mechanisms of cell death Programme and the cross-Unit Fibre Toxicity Programme

Biography:

2011-Present  Deputy Director, MRC Toxicology Unit

2004-Present  Programme Leader, MRC Toxicology Unit

2011-Present  Honorary Chair, Dept. of Molecular & Cell Biology, University of Leicester

1998-2004  MRC Programme Leader-Track Scientist, MRC Toxicology Unit

1998-2004  MRC Visiting Research Fellow, Kimmel Cancer Centre, Philadelphia, USA

1992-1997 Senior Postdoctoral Research Fellow, MRC Toxicology Unit

1989-1992 Wellcome Trust Advanced Training Fellowship Award, University of Surrey

1989 PhD (University of Surrey) Biochemistry – BBSRC-funded iCASE with AstraZeneca

1985 BSc Hons (University of Glasgow) Pharmacology

Research Interests:

Unit Programme:  Molecular Mechanisms of Cell Death

Cell death is a fundamental cellular response that plays a crucial role both during development and in the removal of unwanted or damaged cells following stress, injury or infection. Inappropriate cell death regulation contributes to many human diseases, including cancer and autoimmune and neurodegenerative disorders. Proteins/pathways that control cell death have also been identified as defined nodes that form key decision points to regulate the response to toxic insult.

Our Programme is aimed at understanding the fundamental mechanisms of cell death that regulate life/death decisions at the cellular level. By understanding the underlying molecular and cell biology of these processes, we aim to deliver field-changing mechanistic insights into toxicology and disease.

Our research Objectives are to develop a number of strategies including develop a number of strategies including novel ‘in vitro’ reconstituted models which, combined with an integrated molecular, cell biological and proteomics-based approach, place us in a prime position to examine the molecular determinants of cell death.

In particular, we will employ cutting-edge technologies to:

1. Obtain novel insights on the regulation and molecular architecture of multiprotein signalling complexes that direct cell fate

2. Define signalling networks conferring drug-induced mitochondrial toxicity or cell survival in translational models of hepatotoxicity

3. Selectively target nodes of resistance to cell death in patient-relevant 3D tumour models.

The data generated through these integrated approaches will provide novel insights into the fundamental mechanisms of cell death that underlie the response to toxic injury, thus informing strategies to mitigate toxicity of existing therapies as well as newer agents currently under development.

Publications

Selected publications

Caspase-10 Negatively Regulates Caspase-8-Mediated Cell Death, Switching the Response to CD95L in Favor of NF-κB Activation and Cell Survival Horn S, Hughes MA, Schilling R, Sticht C, Tenev T, Ploesser M, Meier P, Sprick MR, MacFarlane M, Leverkus M Long-Fiber Carbon Nanotubes Replicate Asbestos-Induced Mesothelioma with Disruption of the Tumor Suppressor Gene Cdkn2a (Ink4a/Arf) Chernova T, Murphy FA, Galavotti S, Sun XM, Powley IR, Grosso S, Schinwald A, Zacarias-Cabeza J, Dudek KM, Dinsdale D, Le Quesne J, Bennett J, Nakas A, Greaves P, Poland CA, Donaldson K, Bushell M, Willis AE, MacFarlane M Co-operative and Hierarchical Binding of c-FLIP and Caspase-8: A Unified Model Defines How c-FLIP Isoforms Differentially Control Cell Fate Hughes MA, Powley IR, Jukes-Jones R, Horn S, Feoktistova M, Fairall L, Schwabe John WR, Leverkus M, Cain K, MacFarlane M A role for eukaryotic initiation factor 4B overexpression in the pathogenesis of diffuse large B-cell lymphoma Horvilleur E, Sbarrato T, Hill K, Spriggs RV, Screen M, Goodrem PJ, Sawicka K, Chaplin LC, Touriol C, Packham G, Potter KN, Dirnhofer S, Tzankov A, Dyer MJ, Bushell M, MacFarlane M*, Willis AE A new DISC Model reveals a crucial role for Caspase-8 DED chain assembly in mediating apoptotic cell death Dickens LS, Boyd RS, Jukes-Jones R, Hughes MA, Robinson GL, Fairall L, Schwabe JW, Cain K, MacFarlane M cIAPs block Ripoptosome formation, a RIP1/caspase-8 containing intracellular cell death complex differentially regulated by cFLIP isoforms Feoktistova M, Geserick P, Kellert B, Dimitrova D, Langlais C, Hupe M, Cain K, Hacker G, MacFarlane M, Leverkus M The Ripoptosome, a signaling platform that assembles in response to genotoxic stress and loss of IAPs Tenev T, Bianchi K, Darding M, Broemer M, Langlais C, Wallberg F, Zachariou A, Lopez J, MacFarlane M, Cain K, Meier P A TRAIL-R1-selective Ligand selectively targets Primary Breast Tumour cells for Apoptosis Twiddy D, Naik S, Mistry R, Edwards J, Walker RA, Cohen GM, MacFarlane M Reconstitution of the Death-inducing Signaling Complex (DISC) Reveals a Substrate Switch that Determines CD95-Mediated Death or Survival Hughes MA, Harper N, Butterworth M, Cain K, Cohen GM, MacFarlane M Barriers to effective TRAIL-targeted therapy of malignancy Dyer MJ, MacFarlane M, Cohen GM