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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.

Details Date
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
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
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
O'Brien A, Loftus RM, Pisarska MM, Tobin LM, Bergin R, Wood NAW, Foley C, Mat A, Tinley FC, Bannan C, Sommerville G, Veerapen N, Besra GS, Sinclair LV, Moynagh PN, Lynch L, Finlay DK, O'Shea D Hogan AE, Obesity Reduces mTORC1 Activity in Mucosal-Associated Invariant T Cells, Driving Defective Metabolic and Functional Responses, Journal of Immunology, 202, (12), 2019, p3404 - 3411, Journal Article, PUBLISHED  DOI
Jones N, Vincent EE, Cronin JG, Panetti S, Chambers M, Holm SR, Owens SE, Francis NJ, Finlay DK, Thornton CA, Akt and STAT5 mediate naïve human CD4+ T-cell early metabolic response to TCR stimulation, Nature Communications, 10, (1), 2019, p2042-, Journal Article, PUBLISHED  DOI
Finlay, D.K., N-myristoylation of AMPK controls T cell inflammatory function, Nature Immunology, 20, (3), 2019, p252-254 , Notes: [cited By 0], Journal Article, PUBLISHED  DOI
Katie O'Brien and David. K Finlay, Immunometabolism and Natural Killer cell responses, Nature Reviews Immunology, 19, (5), 2019, p282 - 290, Review Article, PUBLISHED  DOI
Nidhi Kedia-Mehta and David. K Finlay, Competition for nutrients; an emerging role in controlling immune responses, Nature Communications, 10, (1), 2019, p2123-, Review Article, PUBLISHED  DOI
Michelet X, Dyck L, Hogan A, Loftus LM, Duquette D, Wei K, Beyaz S,Tavakkoli A, Foley C, Donnelly R, O'Farrelly C, Raverdeau M, Vernon A, Pettee W, O'Shea D, Nikolajczyk BS, Mills KH, Brenner MB, Finlay DK and Lynch L, Metabolic reprogramming of natural killer cells in obesity prevents cytotoxicity and promotes tumor progression, Nature Immunology, 19, (12), 2018, p1330 - 1340, Journal Article, PUBLISHED  DOI  URL
Zaiatz-Bittencourt, D.K. Finlay, C.M. Gardiner. , Canonical TGF signalling pathway represses human NK cell metabolism, Journal of Immunology, 200, (12), 2018, p3934 - 3941, Journal Article, PUBLISHED
Loftus, R.M. and Assmann, N. and Kedia-Mehta, N. and O'Brien, K.L. and Garcia, A. and Gillespie, C. and Hukelmann, J.L. and Oefner, P.J. and Lamond, A.I. and Gardiner, C.M. and Dettmer, K. and Cantrell, D.A. and Sinclair, L.V. and Finlay, D.K., Amino acid-dependent cMyc expression is essential for NK cell metabolic and functional responses in mice, Nature Communications, 9, (1), 2018, Notes: [cited By 0], Journal Article, PUBLISHED  TARA - Full Text  DOI
David, J. and O'Toole, E. and O'Reilly, K. and Thuery, G. and Assmann, N. and Finlay, D. and Harkin, A., Inhibitors of the NMDA-Nitric Oxide Signaling Pathway Protect Against Neuronal Atrophy and Synapse Loss Provoked by L-alpha Aminoadipic Acid-treated Astrocytes, Neuroscience, 392, 2018, p38-56 , Notes: [cited By 0], Journal Article, PUBLISHED  DOI
Michelet, X. and Dyck, L. and Hogan, A. and Loftus, R.M. and Duquette, D. and Wei, K. and Beyaz, S. and Tavakkoli, A. and Foley, C. and Donnelly, R. and O†Farrelly, C. and Raverdeau, M. and Vernon, A. and Pettee, W. and O†Shea, D. and Nikolajczyk, B.S. and Mills, K.H.G. and Brenner, M.B. and Finlay, D. and Lynch, L., Metabolic reprogramming of natural killer cells in obesity limits antitumor responses, Nature Immunology, 19, (12), 2018, p1330-1340 , Notes: [cited By 1], Journal Article, PUBLISHED  DOI
  

Page 1 of 5
David Finlay, Metabolic regulation of NK cell responses, Seminar, University of Dundee, 8th Feburary, 2019, Prof Doreen Cantrell, Invited Talk, ACCEPTED
David Finlay, Metabolic regulation of NK cell responses, IACR annual conference, Belfast, 21st Feburary, 2019, Invited Talk, ACCEPTED
David Finlay, Metabolic regulation of Natural Killer cell anti-tumour responses, Seminar, Newcastle University, 13th March, 2019, Dr Kevin Marchbank, Invited Talk, ACCEPTED
David Finlay, Metabolic regulation of NK cell responses, Fuelling the immune response: UK immunometabolism meeting 2019, Newcastle, 14th March, 2019, British Society for Immunology's Immunometabolism Affinity Group, Invited Talk, ACCEPTED
David Finlay, NK cell metabolism; Implications for anti-tumour responses, Seminar, Imperial College London, 13th May, 2019, Prof Adam Byrne, Invited Talk, ACCEPTED
David Finlay, Metabolic Regulation of NK cell responses, Immunometabolism: Fundamentals to Prospective New Therapies , Boston, 25th June, 2019, Abcam, Prof Luke O'Neill, Invited Talk, ACCEPTED
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, PRESENTED
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, 21st November, 2018, Ping-Chih Ho, Invited Talk, PRESENTED
David Finlay, Fueling Robust Anti-Tumor NK Cell Responses , Discovery on Target Conference; NK cell based Cancer Immunotherapies, Boston, 26 September, 2018, 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 (funded by ERC-CoG) --Characterising metabolic networks in activated NK cells and how they facilitate anti-tumour NK cell functions.(funded by SFI)