張志禎博士
姓名 張志禎博士
現任 助研究員
所屬單位
腫瘤-宿主交互作用, 癌症代謝, 活性氧化壓力, 腫瘤微環境, 轉移 

PhD, University of Ottawa, Ottawa ON, Canada 2008
BSc, University of British Columbia, Vancouver BC, Canada 2001
 
名片
研究方向/領域

研究方向/領域

解碼癌症與宿主之間的對話

癌症的進展不僅僅是關乎腫瘤細胞自身的變異，更是一場對身體各方面的惡性操控。這場奪取的核心機制在於對異常新陳代謝的適應性變化。當癌細胞不受控制地生長時，會產生大量活性氧為代謝副產物，從而進入氧化應激狀態。這種狀態是一把雙面刃：活性氧既能造成損傷而減慢癌細胞生長，也能啟動特定的訊息傳導讓癌細胞賴以存活和擴散。因此，癌症生物學的一個關鍵問題是，腫瘤如何巧妙地維持這種微妙的平衡。

我們實驗室的核心理念是：癌細胞無法獨自解決這些難題。它們必須與體內正常的非癌細胞及器官進行持續且動態的對話。透過解構這些聯繫機制，我們就能找到新的方法，切斷腫瘤所依賴的支援網絡。我們的研究超越了以腫瘤為中心的觀點，深入探討這些關鍵的腫瘤-宿主交互作用—無論是在局部的微環境中，還是在整體上與遠端器官的互動—如何決定癌症的演變。

我們的研究奠基於氧化應激對癌細胞的影響，高度取決於該腫瘤從何器官而來。以代謝調控因子TIGAR為例，我們發現調控活性氧的水平，可以在腸道中抑制腫瘤生長，但矛盾的是，在胰腺癌中卻會促進其轉移。這種顯著的差異，說明了周圍宿主環境對腫瘤的強大影響。

我們實驗室整合精密的基因改造小鼠模型與先進的類器官體外共培養系統，並利用單細胞RNA定序、CRISPR體細胞基因編輯以及代謝體學等強大技術，去深入剖析這些複雜的交互作用。

我們的目標是將研究成果轉化為更精準、更有效的癌症療法。透過靶向「腫瘤-宿主交互作用」中的宿主端，我們期望能瓦解腫瘤惡性操控宿主的方式，為對抗癌症的進展與抗藥性，開創一個全新的治療契機。


這是一張圖片
Reactive oxygen species (ROS) affect tumour and stromal cells to either impede or promote cancer progression, depending on the integration of the response of all cells in the tumour microenvironment (TME).
From Cheung and Vousden 2022, Nature Review Cancer
經歷
  • 2025-present Assistant Professor, Genomics Research Center, Academia Sinica, Taipei, Taiwan
  • 2022-2025 Principal Research Laboratory Scientist, The Francis Crick Institute, London, UK Group Leader: Karen Vousden
  • 2018-2022 Senior Research Laboratory Scientist, The Francis Crick Institute, London, UK Group Leader: Karen Vousden
  • 2014-2018 Associate Scientist, Cancer Research UK Beatson Institute, Glasgow, UK Group Leader: Karen Vousden
  • 2009-2014 Post-doctoral Fellow, Cancer Research UK Beatson Institute, Glasgow, UK Group Leader: Karen Vousden
榮譽
  • 2009-2012 Canadian Institutes of Health Research (CIHR) Post-doctoral Fellowship
  • 2005-2008 Canadian Institutes of Health Research (CIHR) Doctoral Research Award
  • 2008 The Governor General's Academic Gold Medal, Canada
  • 2005, 2007 Brain Star Award, CIHR Institute of Neurosciences, Mental Health and Addiction
年度 論文名稱
2025 Wittke CI, Cheung EC, Athineos D, Clements N, Butler L, Hughes M, Morrison V, Watt DM, Blyth K, Vousden KH, Humpton TJ, p53 and TIGAR promote redox control to protect against metabolic dysfunction-associated steatohepatitis., JHEP reports : innovation in hepatology, vol. 7(7), 101397, 2025
2024 Cheung EC, Strathdee D, Stevenson D, Coomes J, Blyth K, Vousden KH, Regulation of ROS signaling by TIGAR induces cancer-modulating responses in the tumor microenvironment., Proceedings of the National Academy of Sciences of the United States of America, vol. 121(50), e2416076121, 2024具代表性;
2023 Zani F, Blagih J, Gruber T, Buck MD, Jones N, Hennequart M, Newell CL, Pilley SE, Soro-Barrio P, Kelly G, Legrave NM, Cheung EC, Gilmore IS, Gould AP, Garcia-Caceres C, Vousden KH, The dietary sweetener sucralose is a negative modulator of T cell-mediated responses., Nature, vol. 615(7953), 705-711, 2023具代表性;
2023 Hennequart M, Pilley SE, Labuschagne CF, Coomes J, Mervant L, Driscoll PC, Legrave NM, Lee Y, Kreuzaler P, Macintyre B, Panina Y, Blagih J, Stevenson D, Strathdee D, Schneider-Luftman D, Gronroos E, Cheung EC, Yuneva M, Swanton C, Vousden KH, ALDH1L2 regulation of formate, formyl-methionine, and ROS controls cancer cell migration and metastasis., Cell reports, vol. 42(6), 112562, 2023具代表性;
2022 Cheung EC, Vousden KH, The role of ROS in tumour development and progression., Nature reviews. Cancer, vol. 22(5), 280-297, 2022具代表性;
2022 D'Avola A, Legrave N, Tajan M, Chakravarty P, Shearer RL, King HW, Kluckova K, Cheung EC, Clear AJ, Gunawan AS, Zhang L, James LK, MacRae JI, Gribben JG, Calado DP, Vousden KH, Riches JC, PHGDH is required for germinal center formation and is a therapeutic target in MYC-driven lymphoma., The Journal of clinical investigation, vol. 132(9), e153436, 2022
2021 Hennequart M, Labuschagne CF, Tajan M, Pilley SE, Cheung EC, Legrave NM, Driscoll PC, Vousden KH, The impact of physiological metabolite levels on serine uptake, synthesis and utilization in cancer cells., Nature communications, vol. 12(1), 6176, 2021具代表性;
2021 Tajan M, Hennequart M, Cheung EC, Zani F, Hock AK, Legrave N, Maddocks ODK, Ridgway RA, Athineos D, Suarez-Bonnet A, Ludwig RL, Novellasdemunt L, Angelis N, Li VSW, Vlachogiannis G, Valeri N, Mainolfi N, Suri V, Friedman A, Manfredi M, Blyth K, Sansom OJ, Vousden KH, Serine synthesis pathway inhibition cooperates with dietary serine and glycine limitation for cancer therapy., Nature communications, vol. 12(1), 366, 2021
2020 Cheung EC, DeNicola GM, Nixon C, Blyth K, Labuschagne CF, Tuveson DA, Vousden KH, Dynamic ROS Control by TIGAR Regulates the Initiation and Progression of Pancreatic Cancer., Cancer cell, vol. 37(2), 168-182.e4, 2020具代表性;
2019 Labuschagne CF, Cheung EC, Blagih J, Domart MC, Vousden KH, Cell Clustering Promotes a Metabolic Switch that Supports Metastatic Colonization., Cell metabolism, vol. 30(4), 720-734.e5, 2019具代表性;
2017 Maddocks ODK, Athineos D, Cheung EC, Lee P, Zhang T, van den Broek NJF, Mackay GM, Labuschagne CF, Gay D, Kruiswijk F, Blagih J, Vincent DF, Campbell KJ, Ceteci F, Sansom OJ, Blyth K, Vousden KH, Modulating the therapeutic response of tumours to dietary serine and glycine starvation., Nature, vol. 544(7650), 372-376, 2017具代表性;
2017 Hock AK, Cheung EC, Humpton TJ, Monteverde T, Paulus-Hock V, Lee P, McGhee E, Scopelliti A, Murphy DJ, Strathdee D, Blyth K, Vousden KH, Development of an inducible mouse model of iRFP713 to track recombinase activity and tumour development in vivo., Scientific reports, vol. 7(1), 1837, 2017
2016 Cheung EC, Lee P, Ceteci F, Nixon C, Blyth K, Sansom OJ, Vousden KH, Opposing effects of TIGAR- and RAC1-derived ROS on Wnt-driven proliferation in the mouse intestine., Genes & development, vol. 30(1), 52-63, 2016具代表性;
2015 Lee P, Hock AK, Vousden KH, Cheung EC, p53- and p73-independent activation of TIGAR expression in vivo., Cell death & disease, vol. 6(8), e1842, 2015具代表性;
2014 Lee P, Vousden KH, Cheung EC, TIGAR, TIGAR, burning bright., Cancer & metabolism, vol. 2(1), 1, 2014
2014 Paulus-Hock V, Cheung EC, Roxburgh P, Vousden KH, Hock AK, iRFP is a real time marker for transformation based assays in high content screening., PloS one, vol. 9(6), e98399, 2014
2013 Cheung EC, Athineos D, Lee P, Ridgway RA, Lambie W, Nixon C, Strathdee D, Blyth K, Sansom OJ, Vousden KH, TIGAR is required for efficient intestinal regeneration and tumorigenesis., Developmental cell, vol. 25(5), 463-77, 2013具代表性;
2013 Berkers CR, Maddocks OD, Cheung EC, Mor I, Vousden KH, Metabolic regulation by p53 family members., Cell metabolism, vol. 18(5), 617-33, 2013
2012 Cheung EC, Ludwig RL, Vousden KH, Mitochondrial localization of TIGAR under hypoxia stimulates HK2 and lowers ROS and cell death., Proceedings of the National Academy of Sciences of the United States of America, vol. 109(50), 20491-6, 2012具代表性;
2011 Mor I, Cheung EC, Vousden KH, Control of glycolysis through regulation of PFK1: old friends and recent additions., Cold Spring Harbor symposia on quantitative biology, vol. 76, 211-6, 2011
2010 Cheung EC, Vousden KH, The role of p53 in glucose metabolism., Current opinion in cell biology, vol. 22(2), 186-91, 2010
2009 Bensaad K, Cheung EC, Vousden KH, Modulation of intracellular ROS levels by TIGAR controls autophagy., The EMBO journal, vol. 28(19), 3015-26, 2009
2008 Arbour N, Vanderluit JL, Le Grand JN, Jahani-Asl A, Ruzhynsky VA, Cheung EC, Kelly MA, MacKenzie AE, Park DS, Opferman JT, Slack RS, Mcl-1 is a key regulator of apoptosis during CNS development and after DNA damage., The Journal of neuroscience : the official journal of the Society for Neuroscience, vol. 28(24), 6068-78, 2008
2007 Jahani-Asl A, Cheung EC, Neuspiel M, MacLaurin JG, Fortin A, Park DS, McBride HM, Slack RS, Mitofusin 2 protects cerebellar granule neurons against injury-induced cell death., The Journal of biological chemistry, vol. 282(33), 23788-98, 2007
2007 Cheung EC, McBride HM, Slack RS, Mitochondrial dynamics in the regulation of neuronal cell death., Apoptosis : an international journal on programmed cell death, vol. 12(5), 979-92, 2007
2006 Cheung EC, Joza N, Steenaart NA, McClellan KA, Neuspiel M, McNamara S, MacLaurin JG, Rippstein P, Park DS, Shore GC, McBride HM, Penninger JM, Slack RS, Dissociating the dual roles of apoptosis-inducing factor in maintaining mitochondrial structure and apoptosis., The EMBO journal, vol. 25(17), 4061-73, 2006
2005 Cheung EC, Melanson-Drapeau L, Cregan SP, Vanderluit JL, Ferguson KL, McIntosh WC, Park DS, Bennett SA, Slack RS, Apoptosis-inducing factor is a key factor in neuronal cell death propagated by BAX-dependent and BAX-independent mechanisms., The Journal of neuroscience : the official journal of the Society for Neuroscience, vol. 25(6), 1324-34, 2005
2004 Cregan SP, Arbour NA, Maclaurin JG, Callaghan SM, Fortin A, Cheung EC, Guberman DS, Park DS, Slack RS, p53 activation domain 1 is essential for PUMA upregulation and p53-mediated neuronal cell death., The Journal of neuroscience : the official journal of the Society for Neuroscience, vol. 24(44), 10003-12, 2004