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Dr. David Finlay

Associate Prof. in Immunometabolism (Biochemistry)

Associate Prof. in Immunometabolism (Pharmacy)


I first became captivated by the complexities of cellular signal transduction pathways during my undergraduate biochemistry degree at Trinity College Dublin, which led me to a PhD at the University of Dundee investigating roles for protein kinases such as mTORC1 in the control of metabolic pathways in hepatocytes. I retained a keen interest in protein kinase signalling during my postdoctoral research in Prof. Doreen Cantrell's lab at the University of Dundee. It was during this time in I realised that mTORC1 is a key regulator of CD8 T cell biology largely because it controls cellular metabolic pathways. This research led to one of the first publications in the then emerging field of immunometabolism and motivated me to establish my independent research group to further explore how cellular metabolism is linked to the control of immune cell fate and function. Since 2011, I have secured in excess of €3.4 million research funding and my research has contributed significantly to the current understanding that cellular metabolism is integrally linked to immune cell functions. My research is at the forefront of the Immunometabolism field and I have published high impact studies that have challenged established dogmas. My research group was the first to characterize cellular metabolic pathways in Natural Killer cells to show that the way they metabolize glucose is different to the metabolic pathways described in biochemistry textbooks (Journal of Immunology 2014, Nature Immunology 2017, Nature Communications 2018). My research has also made key contributions to an emerging idea that nutrients are more than just fuels and function as important signals; we showed that glucose controls signal transduction pathways in Dendritic cells (DC) to inhibit DC functions and to limit the induction of CD8 T cell responses (Nature Communications 2017). My contribution to leading this new field of immunometabolism have been recognised with invitations to write review articles for high impact journals including the Journal of Clinical Investigation (2016), Seminars in Immunology (2017) and Nature Reviews Immunology (2019, which have been well received and highly cited. In 2017 I secured an ERC Consolidator Award to study nutrients as key determinants of DC-induced CD8 T cell responses. Successful implementation of this ERC research programme will open new horizons for the study of nutrients as determinants of immune responses. Based on my expertise in the area of lymphocyte metabolism, it is my ambition that this ERC research programme will lead me to further ground-breaking studies assessing the role for nutrients in controlling T cell and NK cell responses in diverse inflammatory situations.
  AMPK   Biochemistry, metabolism   Cell signalling, proliferation & differentiation   C-MYC   GLUCOSE   GLUCOSE METABOLISM   GLUTAMINE   GLUTAMINE METABOLISM   Glycolysis   HIF1-alpha   Immunity   Immunometabolism   LIPID METABOLISM   MITOCHONDRIA   mTOR   OXIDATIVE PHOSPHORYLATION   Regulation of Metabolism   Sterol regulatory element binding protein (Srebp)
 Investigating nutrients as key determinants of DC-induced CD8 T cell responses
 Investigating Natural Killer (NK) cell metabolism as a determinant of NK cell anti-tumour activity
 Characterising the role of mammalian Target Of Rapamcyin Complex 1 (mTORC1)/Srebp1c signaling in directing the differentiation and function of T cell subsets.
 Investigating the impact of cholesterol on anti-tumour NK cell responses.
 Investigating 25-hydroxycholesterol as a novel regulator of Natural Killer cell anti-tumour responses.

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Details Date
Established an Immunometabolism Forum to support immunologists and foster collaboration. Hosts >80 attendees from multiple Schools in TCD, and from RCSI, UCD and NUIM. Sponsorship secured from Agilent 2017-present
Established a global version of the Immunometabolism Forum when we moved online due to the Covid-19 pandemic. Speakers from Dublin, Europe and USA with as many a 250 attendees. 2019-present
Instrumental in establishing Dublin's reputation as hub for excellent Immunometabolism research through activities including the local and global Immunometabolism forums and the Immunometabolism forum YouTube channel 2017-present
Editorial Board for "Immunometabolism" Journal 2018-present
Expert reviewer for Funding agencies including the Wellcome Trust, MRC, BBSRC, Netherlands Organisation for Scientific Research (NWO) and ERC Starter and Advanced grants 2013-present
Expert reviewer for high impact scientific journals including Science, Nature Medicine, Nature Immunology, Cell Metabolism. 2013-present
Sit on the scientific advisory board for Quihan Biotech 2021-present
Scientific advisory role to Irish Biotech company Avectas 2019
Scientific advisory role to Ono Pharma UK Ltd 2016
Details Date From Date To
Irish Society of Immunology 2011 present
British Society of Immunology 2012 present
Biochemical Society 2011 present
TCD Students Biochemical Society 2011 present
Slattery K , Woods E , Zaiatz-Bittencourt V, Marks S , Chew S , Conroy M , Goggin C, MacEochagain C, Kennedy J, Lucas S , Finlay DK , Gardiner CM, TGFβ drives NK cell metabolic dysfunction in human metastatic breast cancer, Journal for Immunotherapy of Cancer , 9, (2), 2021, Journal Article, PUBLISHED  TARA - Full Text  DOI
Jones N, Blagih J, Zani F, Rees A, Hill DG, Jenkins BJ, Bull CJ, Moreira D, Bantan AIM, Cronin JG, Avancini D, Jones GW, Finlay DK, Vousden KH, Vincent EE, Thornton CA, Fructose reprogrammes glutamine-dependent oxidative metabolism to support LPS-induced inflammation, Nature Communications, 22, (12), 2021, p1209-, Journal Article, PUBLISHED  TARA - Full Text  DOI
Dowling JK, Afzal R, Gearing LJ, Cervantes-Silva MP, Annett S, Davis GM, De Santi C, Assmann N, Dettmer K, Gough DJ, Bantug GR, Hamid FI, Nally FK, Duffy CP, Gorman AL, Liddicoat AM, Lavelle EC, Hess C, Oefner PJ, Finlay DK, Davey GP, Robson T, Curtis AM, Hertzog PJ, Williams BRG, McCoy CE , Mitochondrial arginase-2 is essential for IL-10 metabolic reprogramming of inflammatory macrophages, Nature Communications, 12, (1), 2021, p1460-, Journal Article, PUBLISHED  DOI
Elisabeth Littwitz-Salomon Diana Moreira Joe N. Frost Chloe Choi Kevin T. Liou David K. Ahern Simon O'Shaughnessy Bernd Wagner Christine A. Biron Hal Drakesmith Ulf Dittmer David K Finlay , Metabolic requirements of NK cells during the acute response against retroviral infection, Nature Communications, 12, (1), 2021, p5373-, Journal Article, PUBLISHED
Woods E, Zaiatz-Bittencourt V, Bannan C, Bergin C, Finlay DK, Hoffmann M, Brown A, Turner B, Makvandi-Nejad S, Vassilev V, Capone S, Folgori A, Hanke T, Barnes E, Dorrell L, Gardiner CM, Specific human cytomegalovirus signature detected in NK cell metabolic changes post vaccination, NPJ Vaccines, 6, (1), 2021, p112-, Journal Article, PUBLISHED
Timmons GA, Carroll RG, O'Siorain JR, Cervantes-Silva MP, Fagan LE, Cox SL, Palsson-McDermott E, Finlay DK, Vincent EE, Jones N, Curtis AM, The Circadian Clock Protein BMAL1 Acts as a Metabolic Sensor In Macrophages to Control the Production of Pro IL-1β, Frontiers in Immunology, (12), 2021, Journal Article, PUBLISHED
Nidhi Kedia-Mehta, Laura Tobin, Vanessa Zaiatz-Bittencourt, Marta M Pisarska, Conor De Barra, Chloe Choi, Einas Elamin, Donal O'Shea , Clair M Gardiner, David K Finlay, Andrew E Hogan , Cytokine-induced natural killer cell training is dependent on cellular metabolism and is defective in obesity, Blood Advances, 5, (21), 2021, p4447-4455 , Journal Article, PUBLISHED
Slattery, K. and Woods, E. and Zaiatz-Bittencourt, V. and Marks, S. and Chew, S. and Conroy, M. and Goggin, C. and Maceochagain, C. and Kennedy, J. and Lucas, S. and Finlay, D.K. and Gardiner, C.M., TGFβ drives NK cell metabolic dysfunction in human metastatic breast cancer, Journal for ImmunoTherapy of Cancer, 9, (2), 2021, Notes: [cited By 7], Journal Article, PUBLISHED  DOI
O'Brien, K.L. and Assmann, N. and O'Connor, E. and Keane, C. and Walls, J. and Choi, C. and Oefner, P.J. and Gardiner, C.M. and Dettmer, K. and Finlay, D.K., De novo polyamine synthesis supports metabolic and functional responses in activated murine NK cells, European Journal of Immunology, 51, (1), 2021, p91-102 , Notes: [cited By 2], Journal Article, PUBLISHED  DOI
Choi C, Finlay DK, Optimising NK cell metabolism to increase the efficacy of cancer immunotherapy, Stem Cell Res Ther, 12, (1), 2021, Review Article, PUBLISHED
  

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David K Finlay, Nutrients and metabolites controlling NK cell responses , European Federation of Immunological Societies in tour, Online via Zoom, 19 Feb, 2021, EFIS, Invited Talk, PRESENTED
David Finlay, Natural Killer cell and cancer cell metabolism intertwined, EMBO Workshop on Cancer Immunometabolism, Sitges, Spain, 29th Nov - 1st Dec, 2021, EMBO, Invited Talk, PRESENTED
David Finlay, Science, Nutrients and Immunity. What is the stress about?, ISI Early Career Researchers Meeting, Dublin, 25th Nov, 2021, Irish Society of Immunology, Invited Talk, PRESENTED
David Finlay, Nutrients and Metabolites controlling Natural Killer cell responses, Leeds Institute of Medical Research Virtual seminar series, Online, 21st Oct, 2021, Dr Robert Salmond, Invited Talk, PRESENTED
David Finlay, Nutrients and Metabolites controlling Natural Killer cell responses, Agilent Technologies Webinar Series, Online, 18th Nov, 2021, Agilent Technologies, Invited Talk, PRESENTED
David Finlay, Nutrients and Metabolites controlling lymphocyte responses, Portuguese Society of Immunology annual meeting, Online, 21st May, 2021, Portuguese Society of Immunology , Invited Talk, PRESENTED
David K Finlay, What fuels Cancer Killers, Cambridge Scientific Society Seminar series, Cambridge, UK, 2020, Cambridge Scientific Society (Student society), Invited Talk, PUBLISHED
David K Finlay, Nutrients and metabolites controlling lymphocyte responses , Seminar, Centro de Biología Molecular Severo Ochoa, 28 Feb, 2020, Centro de Biología Molecular Severo Ochoa, Invited Talk, PRESENTED
David K Finlay, Shaping immune responses by targeting Immunometabolism , British Transplantation Society conference, Belfast, 5 March, 2020, Invited Talk, PUBLISHED
David K Finlay, Nutrients and metabolites controlling lymphocyte responses , ImmunoMetNet meeting, Online via Zoom, 8 April, 2020, Jan van den Bossche, Invited Talk, PUBLISHED

  

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Award Date
Fellow of Trinity College Dublin 2018
European Research Council Consolidator Award 2017
Science Foundation Ireland - Career Development Award 2014
Marie Sklodowska Curie - Career Integration Fellowship 2012
Our immune system is important for our health protecting us from infection/cancer, but inappropriate immune responses cause us harm. Diverse diseases could be treated through therapeutic manipulation of our immune systems. My research group wants to understand how to control immune cells and is now revealing the importance of cellular metabolism. We are revealing novel strategies to modulate immune cell function through targeting cellular metabolism and new therapeutic opportunities are being explored. Our data show following activation Natural killer (NK) cells, lymphocytes with important anti-cancer and anti-viral functions, undergo robust metabolic changes. We have identified the key metabolic regulators of this metabolic response to be mTORC1, cMyc and Srebp. Directly disrupting metabolic pathways in NK cells or interfering with the function of these metabolic regulators severely inhibits NK cell anti-cancer and anti-viral functions, including target cell killing. We are exploring how NK cell metabolism might be manipulated to improve NK cell-based anti-cancer immunotherapies through a Enterprise Ireland Innovative partnership with a Galway-based company ONK Therapeutics. In contrast to lymphocytes, mTORC1 and glucose metabolism actually inhibit the function of Dendritic Cells (DC). We made the novel discovery that starving DC of glucose results in increased proinflammatory outputs and enhanced DC-induced T cell responses. This study highlights the complex relationship between nutrient availability and the induction of immune responses. An important next step will be investigating the distribution of nutrients in vivo, to determine which immune cells are nutrient replete and those that are deprived of nutrients. Ongoing projects include: --Investigating nutrients as key determinants of DC-induced CD8 T cell responses (funded by ERC-CoG) --Characterising how the tumour microenvironment disrupts NK cell metabolism towards engineering NK cells for improved metabolic resilience and improved met to improve anti-tumour NK cell therapies.(funded by Enterprise Ireland and ONK Therapeutics)