Daniel Puleston, PhD
- ASSISTANT PROFESSOR | Oncological Sciences
Research Topics:Cancer, Cell Biology, Cellular Differentiation, Cellular Immunity, Immunology, Inflammation, Lymphocytes, Macrophage, Metabolism, Metabolomics, T Cells
Daniel Puleston, PhD is an Assistant Professor of Oncological Sciences and a member of the Precision Immunology Institute and the Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai. Dr. Puleston received his doctorate and degrees in immunology from the University of Oxford followed by post-doctoral training at the Max Planck Institute for Immunology in Germany and Johns Hopkins University on a Sir Henry Wellcome Award. Dr. Puleston’s past work has elucidated how immune memory is formed and how poor long-lasting immunity in older individuals can be overcome by targeting cellular metabolism. His recent studies revealed how certain metabolic modalities are pivotal for the ability of T cells and macrophages to differentiate into distinct functional subsets – a key feature of immune cells facilitating their capacity to respond flexibly to numerous environmental threats. The Puleston Lab seeks to understand how metabolic factors shape immune cell function in healthy tissues and disease. Major research themes center around metabolic factors in tumor microenvironments including metabolic control of immune cell differentiation and acquisition of tissue-specific identities.
Multi-Disciplinary Training AreaCancer Biology [CAB]
PhD, University of Oxford
Johns Hopkins University
Max Planck Institute of Immunobiology & Epigenetics
University of Oxford
Sir Henry Wellcome Fellowship
EMBO Long-Term Fellowship
EPA Cephalosporin Junior Research Fellowship
Prize Ph.D in Medicine, University of Oxford
The lab’s goal is to understand how immunity is fueled. In the Puleston Lab, we believe that by turning our attention to cellular metabolism, we can decode key underlying principles of immune cell biology. Most importantly, by investigating the intersection of metabolism, pathology, and the immune system, we strive to expose novel metabolic vulnerabilities that can be utilized for disease prevention and therapy. Major areas of investigation include: - How perturbations in cellular metabolism drive tumorigenesis - How local metabolic factors instruct the acquisition of tissue-specific signatures - Metabolic pathways governing immune cell dysfunction in tumors - Metabolic regulation of pluri- and multipotency in stem and progenitor cells
Puleston DJ, Baixauli F, Sanin DE, Edwards-Hicks J, Villa M, Kabat AM, Kamiński MM, Stanckzak M, Weiss HJ, Grzes KM, Piletic K, Field CS, Corrado M, Haessler F, Wang C, Musa Y, Schimmelpfennig L, Flachsmann L, Mittler G, Yosef N, Kuchroo VK, Buescher JM, Balabanov S, Pearce EJ, Green DR, Pearce EL. Polyamine metabolism is a central determinant of helper T cell lineage fidelity. Cell 2021 08; 184(16).
Puleston DJ, Buck MD, Klein Geltink RI, Kyle RL, Caputa G, O'Sullivan D, Cameron AM, Castoldi A, Musa Y, Kabat AM, Zhang Y, Flachsmann LJ, Field CS, Patterson AE, Scherer S, Alfei F, Baixauli F, Austin SK, Kelly B, Matsushita M, Curtis JD, Grzes KM, Villa M, Corrado M, Sanin DE, Qiu J, Pällman N, Paz K, Maccari ME, Blazar BR, Mittler G, Buescher JM, Zehn D, Rospert S, Pearce EJ, Balabanov S, Pearce EL. Polyamines and eIF5A Hypusination Modulate Mitochondrial Respiration and Macrophage Activation. Cell metabolism 2019 08; 30(2).
Puleston DJ, Pearce EL. Appetite for Arginine: Metabolic Control of Macrophage Hunger. Cell metabolism 2020 03; 31(3).
Puleston DJ, Villa M, Pearce EL. Ancillary Activity: Beyond Core Metabolism in Immune Cells. Cell metabolism 2017 Jul; 26(1).
Wagner A, Wang C, Fessler J, DeTomaso D, Avila-Pacheco J, Kaminski J, Zaghouani S, Christian E, Thakore P, Schellhaass B, Akama-Garren E, Pierce K, Singh V, Ron-Harel N, Douglas VP, Bod L, Schnell A, Puleston D, Sobel RA, Haigis M, Pearce EL, Soleimani M, Clish C, Regev A, Kuchroo VK, Yosef N. Metabolic modeling of single Th17 cells reveals regulators of autoimmunity. Cell 2021 08; 184(16).
O'Sullivan D, Stanczak MA, Villa M, Uhl FM, Corrado M, Klein Geltink RI, Sanin DE, Apostolova P, Rana N, Edwards-Hicks J, Grzes KM, Kabat AM, Kyle RL, Fabri M, Curtis JD, Buck MD, Patterson AE, Regina A, Field CS, Baixauli F, Puleston DJ, Pearce EJ, Zeiser R, Pearce EL. Fever supports CD8 effector T cell responses by promoting mitochondrial translation. Proceedings of the National Academy of Sciences of the United States of America 2021 06; 118(25).
Klein Geltink RI, Edwards-Hicks J, Apostolova P, O'Sullivan D, Sanin DE, Patterson AE, Puleston DJ, Ligthart NA, Buescher JM, Grzes KM, Kabat AM, Stanczak M, Curtis JD, Hässler F, Uhl FM, Fabri M, Zeiser R, Pearce EJ, Pearce EL. Metabolic conditioning of CD8 effector T cells for adoptive cell therapy. Nature metabolism 2020 08; 2(8).
Field CS, Baixauli F, Kyle RL, Puleston DJ, Cameron AM, Sanin DE, Hippen KL, Loschi M, Thangavelu G, Corrado M, Edwards-Hicks J, Grzes KM, Pearce EJ, Blazar BR, Pearce EL. Mitochondrial Integrity Regulated by Lipid Metabolism Is a Cell-Intrinsic Checkpoint for Treg Suppressive Function. Cell metabolism 2020 02; 31(2).
Cameron AM, Castoldi A, Sanin DE, Flachsmann LJ, Field CS, Puleston DJ, Kyle RL, Patterson AE, Hässler F, Buescher JM, Kelly B, Pearce EL, Pearce EJ. Inflammatory macrophage dependence on NAD salvage is a consequence of reactive oxygen species-mediated DNA damage. Nature immunology 2019 04; 20(4).
Puleston DJ, Zhang H, Powell TJ, Lipina E, Sims S, Panse I, Watson AS, Cerundolo V, Townsend AR, Klenerman P, Simon AK. Autophagy is a critical regulator of memory CD8(+) T cell formation. eLife 2014 Nov; 3.
Puleston DJ, Simon AK. Autophagy in the immune system. Immunology 2014 Jan; 141(1).
Salio M, Puleston DJ, Mathan TS, Shepherd D, Stranks AJ, Adamopoulou E, Veerapen N, Besra GS, Hollander GA, Simon AK, Cerundolo V. Essential role for autophagy during invariant NKT cell development. Proceedings of the National Academy of Sciences of the United States of America 2014 Dec; 111(52).
Puleston D. Detection of Mitochondrial Mass, Damage, and Reactive Oxygen Species by Flow Cytometry. Cold Spring Harbor protocols 2015 Sep; 2015(9).
Puleston D, Phadwal K, Watson AS, Soilleux EJ, Chittaranjan S, Bortnik S, Gorski SM, Ktistakis N, Simon AK. Techniques for the Detection of Autophagy in Primary Mammalian Cells. Cold Spring Harbor protocols 2015 Sep; 2015(9).
Zhang H, Puleston DJ, Simon AK. Autophagy and Immune Senescence. Trends in molecular medicine 2016 08; 22(8).
Watson AS, Riffelmacher T, Stranks A, Williams O, De Boer J, Cain K, MacFarlane M, McGouran J, Kessler B, Khandwala S, Chowdhury O, Puleston D, Phadwal K, Mortensen M, Ferguson D, Soilleux E, Woll P, Jacobsen SE, Simon AK. Autophagy limits proliferation and glycolytic metabolism in acute myeloid leukemia. Cell death discovery 2015 Aug; 1.
Stranks AJ, Hansen AL, Panse I, Mortensen M, Ferguson DJ, Puleston DJ, Shenderov K, Watson AS, Veldhoen M, Phadwal K, Cerundolo V, Simon AK. Autophagy Controls Acquisition of Aging Features in Macrophages. Journal of innate immunity 2015; 7(4).
Jabir MS, Hopkins L, Ritchie ND, Ullah I, Bayes HK, Li D, Tourlomousis P, Lupton A, Puleston D, Simon AK, Bryant C, Evans TJ. Mitochondrial damage contributes to Pseudomonas aeruginosa activation of the inflammasome and is downregulated by autophagy. Autophagy 2015; 11(1).
Henson SM, Lanna A, Riddell NE, Franzese O, Macaulay R, Griffiths SJ, Puleston DJ, Watson AS, Simon AK, Tooze SA, Akbar AN. p38 signaling inhibits mTORC1-independent autophagy in senescent human CD8⁺ T cells. The Journal of clinical investigation 2014 Sep; 124(9).
Jabir MS, Ritchie ND, Li D, Bayes HK, Tourlomousis P, Puleston D, Lupton A, Hopkins L, Simon AK, Bryant C, Evans TJ. Caspase-1 cleavage of the TLR adaptor TRIF inhibits autophagy and β-interferon production during Pseudomonas aeruginosa infection. Cell host & microbe 2014 Feb; 15(2).