Stephen Tait - Mitochondria and Cell Death

University of Glasgow / Beatson Associate

Introduction

TaitS

Cell death is a key tumour suppressor mechanism that must be inhibited in order for cancer to develop. Sensitivity to cell death also governs therapeutic efficacy because anti-cancer therapies often act by killing cells. The major form of programmed cell death is apoptosis, a process in which mitochondria play an essential role. Our research focuses upon understanding how mitochondria control cell death and addressing how this is deregulated in cancer. Clinical translation of our findings should lead to improvements of existing therapies and development of new approaches to enable tumour selective killing.

PhD Studentship available with Dr Stephen Tait: Targeting immunogenic cell death to treat cancer

The best way to treat cancer is to kill it - along these lines, many cancer treatments work by triggering apoptosis. While effective, cell death based therapies often fail due to incomplete killing that allows tumour outgrowth. Additionally, sub-lethal apoptotic signalling by cancer therapy can cause unwanted DNA damage in normal cells. Importantly, our recent data shows that killing cancer cells in the presence of caspase inhibitors prevents unwanted DNA damage and makes the dying cell stimulate anti-tumour immunity. Excitingly, this often leads to complete tumour regression. Stemming from our findings, this PhD project will address two key questions: 1) how does killing cancer cells in caspase-deficient conditions make them immunogenic? 2) in which tumour-types can we exploit this type of cell killing as a therapeutic approach? To address these questions this PhD will apply a variety of cutting-edge approaches including live-cell microscopy, CRISPR/Cas9 genome editing and in vivo cancer models.

Relevant publications: Nat Rev Cancer. 2016,16:539-48; Nat Commun. 2016, 7:10538; Mol Cell. 2015, 57:860-72; Br J Cancer. 2015, 112:957-62

For more information: Dr Tait's website or e-mail stephen.tait@glasgow.ac.uk

The Cancer Research UK Beatson Institute supports cutting edge research into the molecular mechanisms of cancer development and is one of the leading research institutes in Europe. The Institute provides an outstanding research environment, underpinned by state-of-the-art core services and advanced technologies, with special emphasis on imaging, metabolomics, and in vivo models.

Please apply with cover letter and C.V. to stephen.tait@glasgow.ac.uk

Application deadline: August 1st, 2017


University of Glasgow webpage

Lab Report

 

Biography

Education and qualifications

2001: PhD, University of Sussex, Institute for Animal Health, Pirbright Lab
1996: BSc, Medical Microbiology, University of Edinburgh

Appointments

2012-present: Group Leader, CRUK Beatson Institute/University of Glasgow
2005-2011: Postdoctoral Fellow with Doug Green, St Jude Children's Hospital, Memphis, USA
2003-2005: Postdoctoral Fellow with Jannie Borst, The Netherlands Cancer Institute, Amsterdam
2001-2003: Marie Curie Postdoctoral Fellow, The Netherlands Cancer Institute, Amsterdam

Recent Publications

2017

Correia-Melo C, Ichim G, Tait SW, Passos JF. Depletion of mitochondria in mammalian cells through enforced mitophagy. Nat Protoc 12: 183-194, 2017

Daniels BP, Snyder AG, Olsen TM, Orozco S, Oguin TH, 3rd, Tait SW, Martinez J, Gale M, Jr., Loo YM, Oberst A. RIPK3 Restricts Viral Pathogenesis via Cell Death-Independent Neuroinflammation. Cell 169: 301-313 e11, 2017

Gutierrez KD, Davis MA, Daniels BP, Olsen TM, Ralli-Jain P, Tait SW, Gale M, Jr., Oberst A (2017) MLKL Activation Triggers NLRP3-Mediated Processing and Release of IL-1beta Independently of Gasdermin-D. J Immunol

Simon HU, Friis R, Tait SW, Ryan KM. Retrograde signaling from autophagy modulates stress responses. Sci Signal 10: pii: eaag2791, 2017

Woodham EF, Paul NR, Tyrrell B, Spence HJ, Swaminathan K, Scribner MR, Giampazolias E, Hedley A, Clark W, Kage F, Marston DJ, Hahn KM, Tait SW, Larue L, Brakebusch CH, Insall RH, Machesky LM. Coordination by Cdc42 of Actin, Contractility, and Adhesion for Melanoblast Movement in Mouse Skin. Curr Biol 27: 624-637, 2017

2016

Correia-Melo C, Ichim G, Tait SW, Passos JF. Depletion of mitochondria in mammalian cells through enforced mitophagy. Nat Protoc 2017; 12: 183-94. doi: 10.1038/nprot.2016.159. Epub 22 Dec 2016Correia-Melo C, Marques FD, Anderson R, Hewitt G, Hewitt R, Cole J, Carroll BM, Miwa S, Birch J, Merz A, Rushton MD, Charles M, Jurk D, Tait SW, Czapiewski R, Greaves L, Nelson G, Bohlooly-Y M, Rodriguez-Cuenca S, Vidal-Puig A, Mann D, Saretzki G, Quarato G, Green DR, Adams PD, von Zglinicki T, Korolchuk VI, Passos JF. Mitochondria are required for pro-ageing features of the senescent phenotype. EMBO J. 2016 Apr 1;35(7):724-42

Lopez J, Bessou M, Riley JS, Giampazolias E, Todt F, Rochegue T, Oberst A, Green DR, Edlich F, Ichim G, Tait SWG. Mito-priming as a method to engineer Bcl-2 addiction. Nat Commun 2016; 7: 10538

Pecot J, Maillet L, Le Pen J, Vuillier C, Trecesson SC, Fetiveau A, Sarosiek KA, Bock FJ, Braun F, Letai A, Tait SW, Gautier F, Juin PP. Tight Sequestration of BH3 Proteins by BCL-xL at Subcellular Membranes Contributes to Apoptotic Resistance. Cell Rep 17: 3347-3358, 2016

Giampazolias E, Tait SWG. Mitochondria and the hallmarks of cancer. FEBS J 283: 803-14, 2016

Ichim G, Tait SWG. A fate worse than death: apoptosis as an oncogenic process. Nat Rev Cancer 16: 539-48, 2016

Klionsky DJ, Abdelmohsen K, Abe A, Abedin MJ, Abeliovich H, Acevedo Arozena A, Adachi H, Adams CM, Adams PD, Adeli K, Adhihetty PJ, Adler SG, Agam G, Agarwal R, Aghi MK, Agnello M, Agostinis P, Aguilar PV, Aguirre-Ghiso J, Airoldi EM et al. Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). Autophagy 12: 1-222, 2016

Oberst A, Ichim G, Tait SWG. Mitochondrial Permeabilization: From Lethality to Vitality. In: Cell Death in Biology and Diseases pp 213-26, 2016 (Ed Hockenbery DM)

Riley JS, Tait SWG. Mechanisms of mitophagy: putting the powerhouse into the doghouse. Biol Chem 397: 617-35, 2016

2015

Baudot AD, Haller M, Mrschtik M, Tait SW, Ryan KM. Using enhanced-mitophagy to measure autophagic flux. Methods 75: 105-11, 2015

Dikovskaya D, Cole JJ, Mason SM, Nixon C, Karim SA, McGarry L, Clark W, Hewitt RN, Sammons MA, Zhu J, Athineos D, Leach JD, Marchesi F, van Tuyn J, Tait SW, Brock C, Morton JP, Wu H, Berger SL, Blyth K, Adams PD. Mitotic Stress Is an Integral Part of the Oncogene-Induced Senescence Program that Promotes Multinucleation and Cell Cycle Arrest. Cell Rep 2015; 12: 1483-96

Galluzzi L, Bravo-San Pedro JM, Vitale I, Aaronson SA, Abrams JM, Adam D, Alnemri ES, Altucci L, Andrews D, Annicchiarico-Petruzzelli M, Baehrecke EH, Bazan NG, Bertrand MJ, Bianchi K, Blagosklonny MV, Blomgren K, Borner C, Bredesen DE, Brenner C, Campanella M, Candi E, Cecconi F, Chan FK, Chandel NS, Cheng EH, Chipuk JE, Cidlowski JA, Ciechanover A, Dawson TM, Dawson VL, De Laurenzi V, De Maria R, Debatin KM, Di Daniele N, Dixit VM, Dynlacht BD, El-Deiry WS, Fimia GM, Flavell RA, Fulda S, Garrido C, Gougeon ML, Green DR, Gronemeyer H, Hajnoczky G, Hardwick JM, Hengartner MO, Ichijo H, Joseph B, Jost PJ, Kaufmann T, Kepp O, Klionsky DJ, Knight RA, Kumar S, Lemasters JJ, Levine B, Linkermann A, Lipton SA, Lockshin RA, Lopez-Otin C, Lugli E, Madeo F, Malorni W, Marine JC, Martin SJ, Martinou JC, Medema JP, Meier P, Melino S, Mizushima N, Moll U, Munoz-Pinedo C, Nunez G, Oberst A, Panaretakis T, Penninger JM, Peter ME, Piacentini M, Pinton P, Prehn JH, Puthalakath H, Rabinovich GA, Ravichandran KS, Rizzuto R, Rodrigues CM, Rubinsztein DC, Rudel T, Shi Y, Simon HU, Stockwell BR, Szabadkai G, Tait SW, Tang HL, Tavernarakis N, Tsujimoto Y, Vanden Berghe T, Vandenabeele P, Villunger A, Wagner EF, Walczak H, White E, Wood WG, Yuan J, Zakeri Z, Zhivotovsky B, Melino G, Kroemer G. Essential versus accessory aspects of cell death: recommendations of the NCCD 2015. Cell Death Differ 22: 58-73, 2015

Ichim G, Lopez J, Ahmed SU, Muthalagu N, Giampazolias E, Delgado ME, Haller M, Riley JS, Mason SM, Athineos D, Parsons MJ, van de Kooij B, Bouchier-Hayes L, Chalmers AJ, Rooswinkel RW, Oberst A, Blyth K, Rehm M, Murphy DJ, Tait SW. Limited mitochondrial permeabilization causes DNA damage and genomic instability in the absence of cell death. Mol Cell 57: 860-72, 2015

Lopez J, Tait SW. Mitochondrial apoptosis: killing cancer using the enemy within. Br J Cancer 112: 957-62, 2015

Todt F, Cakir Z, Reichenbach F, Emschermann F, Lauterwasser J, Kaiser A, Ichim G, Tait SWG, Frank S, Langer HF, Edlich F. Differential retrotranslocation of mitochondrial Bax and Bak. EMBO J 34: 67-80, 2015

2014

Haller M, Hock AK, Giampazolias E, Oberst A, Green DR, Debnath J, Ryan KM, Vousden KH, Tait SWG. Ubiquitination and proteasomal degradation of ATG12 regulates its pro-apoptotic activity, Autophagy 10: 2269-78, 2014

Ichim G, Tait SW. Necroptosis: fifty shades of RIPKs. Mol Cell Oncol 2015; 2. doi: 10.4161/23723548.2014.965638. Epub 2014 Nov 7

Lopez J, Tait SW. Killing the Killer: PARC/CUL9 promotes cell survival by destroying cytochrome C. Sci Signal 7: pe17, 2014

Orozco S, Yatim N, Werner MR, Tran H, Gunja SY, Tait SW, Albert ML, Green DR, Oberst A. RIPK1 both positively and negatively regulates RIPK3 oligomerization and necroptosis. Cell Death Differ 21: 1511-21, 2014

Tait SW, Ichim G, Green DR. Die another way--non-apoptotic mechanisms of cell death. J Cell Sci 127: 2135-44, 2014

2013

Tait SW, Oberst A, Quarato G, Milasta S, Haller M, Wang R, Karvela M, Ichim G, Yatim N, Albert ML, Kidd G, Wakefield R, Frase S, Krautwald S, Linkermann A, Green DR. Widespread mitochondrial depletion via mitophagy does not compromise necroptosis. Cell Reports 5: 878-85, 2013

Tait S. DNA: leukemia's secret weapon of bone mass destruction. Oncogene 32: 5199-200, 2013

Tait SWT, Green DR. Mitochondrial regulation of cell death. Cold Spring Harbor Perspectives in Biology 5: a008706, 2013

2012

Bender CE, Fitzgerald P, Tait SWG, Llambi F, McStay GP, Tupper DO, Pellettieri J, Alvarado AS, Salvesen GS, Green DR. Mitochondrial pathway of apoptosis is ancestral in metazoans. PNAS 109: 4904-9, 2012

Tait SWG, Green DR. Mitochondria and cell signalling. J Cell Sci 125: 807-15, 2012

Lab Members

tait group

Post-docs

Florian Bock
Kirsteen Campbell
Kai Cao
Joel Riley

Scientific Officer

Catherine Cloix

Clinical Research Fellow

Anna Koessinger (CRUK Centre)

PhD Students

Evangelos Giampazolias (CRUK Centre)
Alba Roca

Research

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Seminars

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