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Dr. David Finlay

Assistant Prof. in Immunometabolism (Biochemistry)

Assistant 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 characterise cellular metabolic pathways in Natural Killer cells to show that the way they metabolise glucose is different to the metabolic pathways described in biochemistry textbooks (Journal of Immunology 2014, Nature Immunology 2017, Nature Communications [under final review] 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 (2018) and Nature Communications (2018, in preparation), 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.

Details Date
Expert reviewer for Funding agencies including the Wellcome Trust, MRC, BBSRC and ERC. (16 grants) 2013-present
Expert reviewer for high impact scientific journals including Nature Medicine, Nature Immunology, Cell Metabolism, Nature Communications and Journal of Clinical Investigation. (2013-2016 - 20 articles, 2017 - 14 articles) 2013-present
Writing upon invitation review articles (8 articles) 2011-present
Established an Immunometabolism Forum to support immunologists and foster collaboration. Hosts >80 attendees from multiple Schools in TCD, and from RCSI and NUIM. Sponsorship secured from Agilent 2017-present
External reviewer for PhD viva voce examinations (Swansea University 2016, University of Vienna 2016, Leiden University 2018) 2016- present
Organised for world-respected scientists to visit and give research seminars within our Institute. (5 visits, 2012-2018) 2012-present
Regularly act as chairperson at international conferences including Keystone Immunnometabolism conferences. 2015-present
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
Róisín M. Loftus, Nadine Assmann, Nidhi Kedia-Mehta, Katie O'Brien, Arianne Garcia, Conor Gillespie, Jens L. Hukelmann, Clair M. Gardiner, Katja Dettmer, Doreen A. Cantrell, Linda V. Sinclair, David K. Finlay, Amino acid-dependent cMyc signalling is essential for murine NK cell metabolic and functional responses, Nature Communications, Revised manuscript, (Under Review), 2018, Notes: [Manuscript revised to address reviewers comments and resubmitted], Journal Article, SUBMITTED
Zaiatz-Bittencourt, D.K. Finlay, C.M. Gardiner. , Canonical TGF signalling pathway represses human NK cell metabolism, Journal of Immunology, Revised manuscript, (Under Review), 2018, Notes: [Manuscript revised to address reviewers comments and resubmitted,], Journal Article, SUBMITTED
Nadine Assmann, Katie L. O'Brien, Raymond P. Donnelly, Lydia Dyck, Vanessa Zaiatz-Bittencourt, Róisín M. Loftus, Paul Heinrich, Peter J. Oefner, Lydia Lynch, Clair M. Gardiner, Katja Dettmer & David K. Finlay, Srebp-controlled glucose metabolism is essential for NK cell functional responses, Nature Immunology, 18, (11), 2017, p1197 - 1206, Journal Article, PUBLISHED  DOI  URL
Simon J. Lawless, Nidhi Kedia-Mehta, Jessica F. Walls, Ryan McGarrigle, Orla Convery, Linda V. Sinclair, Maria N. Navarro, James Murray, David K. Finlay, Glucose represses dendritic cell-induced T cell responses, Nature Communications, (8), 2017, p15620-, Journal Article, PUBLISHED  TARA - Full Text  DOI  URL
Tobin, Laura M and Mavinkurve, Meenal and Carolan, Eirin and Kinlen, David and O'Brien, Eoin C and Little, Mark A and Finlay, David K and Cody, Declan and Hogan, Andrew E and O'Shea, Donal, NK cells in childhood obesity are activated, metabolically stressed, and functionally deficient, JCI insight, 2, (24), 2017, pe94939 , Journal Article, PUBLISHED  DOI
Clair M. Gardiner and David K. Finlay, What Fuels Natural Killers? Metabolism and NK Cell Responses, Frontiers in Immunolobgy, 8, 2017, Review Article, PUBLISHED  TARA - Full Text  DOI
Shehata HM, Murphy AJ, Lee MKS, Gardiner CM, Crowe SM, Sanjabi S, Finlay DK, Palmer CS, Sugar or Fat?-Metabolic Requirements for Immunity to Viral Infections, Frontiers in Immunology, 8, 2017, p1311-, Review Article, PUBLISHED  TARA - Full Text  DOI
Roisin Loftus, Amino acid-dependent mTORC1 and cMyc signaling is essential for Natural Killer cell metabolic and functional responses, Trinity College Dublin, 2017, Thesis, ACCEPTED
Keating SE, Zaiatz-Bittencourt V, Loftus RM, Keane C, Brennan K, Finlay DK, Gardiner CM., Metabolic Reprogramming Supports IFN-γ Production by CD56bright NK Cells., Journal of Immunology, 196, (6), 2016, p2552 - 2560, Journal Article, PUBLISHED  DOI  URL
Viel S, Marçais A, Guimaraes FS, Loftus R, Rabilloud J, Grau M, Degouve S, Djebali S, Sanlaville A, Charrier E, Bienvenu J, Marie JC, Caux C, Marvel J, Town L, Huntington ND, Bartholin L, Finlay D, Smyth MJ, Walzer T, TGF-β inhibits the activation and functions of NK cells by repressing the mTOR pathway., Science Signalling, 9, 2016, pra19-, Journal Article, PUBLISHED  DOI

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David Finlay, Metabolic regulation of NK cell anti-tumour responses, Natural Killer Cell Symposium 2018 - of the German Society for Immunology , Hamburg, Germany, 10th September, 2018, Keynote Speaker, Notes: [Keynote speaker], Invited Talk, ACCEPTED
David Finlay, What fuels Natural Killer Cell anti-tumour responses., Institute Seminar Series, University of Dundee, 28th Feburary, 2018, Invited Talk, ACCEPTED
David Finlay, Metabolic regulation of Immune responses., Institute Seminar Series, University of Lausanne, 7th November, 2018, Ping-Chih Ho, Invited Talk, ACCEPTED
David Finlay, Srebp-controlled glucose metabolism is essential for NK cell functional response, Annual meeting of the French Society for Immunology, Reims, France., 9th November , 2017, Notes: [Plenary Session Speaker], Invited Talk, PRESENTED
David Finlay, What fuels Natural Killers? Metabolic regulation of NK cells, Institute Seminar, Heinrich Pette Institute, Hamburg, Germany, April, 2017, Invited Talk, PRESENTED
David Finlay, Glucose in the regulation of DC-induced CD8 T cell responses, Institute Seminar Series, Department of Pathology, University of Cambridge, 8th November, 2017, Invited Talk, PRESENTED
David Finlay, Srebp-controlled glucose metabolism is essential for NK cell functional response, Microbes, Immunity and Metabolism, Paris, France, 16th November , 2017, Instituit Pasteur, Invited Talk, PRESENTED
David Finlay, Glucose represses Dendritic Cell-induced T cell responses, Institute Seminar, Medical University of Vienna, Institute of Medical GeneticsUniversity of , 6th December, 2016, Thomas Weichhart, PhD, Invited Talk, PRESENTED
David Finlay, Metabolic regulation of Natural Killer Cells , American Association of Immunology (AAI), New Orleans, 9 May, 2015, Invited Talk, PRESENTED
David Finlay, Nutrients control immune responses , Irish Society of Immunology, Trinity College Dublin, September , 2015, Invited Talk, PRESENTED


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Award Date
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. Our research shows that the cellular fuels available to immune cells and the ways that these fuels are used have a big impact on their function. 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 functions, undergo a robust metabolic response leading to elevated levels of glycolysis and oxidative phosphorylation. 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 functions; IFN-gamma production, granzyme b expression and tumour cell killing. We are exploring how NK cell metabolism might be manipulated to improve NK cell-based anti-cancer immunotherapies. 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 --Characterising metabolic networks in activated NK cells and how they facilitate anti-tumour NK cell functions.