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Dr. Vincent Kelly
Assoc Prof/Academic Co-Ordinator, Biochemistry

Publications and Further Research Outputs

Peer-Reviewed Publications

Koen van Wijk, Takeru Akabane, Tomohiro Kimura, Shinichi Saitoh, Satoshi Okano, Vincent P. Kelly, Michiaki Takagi, Ken Kodama, Kiwamu Takahashi, Tohru Tanaka, Motowo Nakajima, Osamu Nakajima, Heterozygous disruption of ALAS1 in mice causes an accelerated age-dependent reduction in free heme, but not total heme, in skeletal muscle and liver, Archives of Biochemistry and Biophysics, 697, 2021, p108721 Journal Article, 2021

Ghanim M, Relitti N, McManus G, Butini S, Cappelli A, Campiani G, Mok KH, Kelly VP, A non-toxic, reversibly released imaging probe for oral cancer that is derived from natural compounds., Scientific reports, 2021 Journal Article, 2021

Fergus C, Al-Qasem M, Cotter M, McDonnell CM, Sorrentino E, Chevot F, Hokamp K, Senge MO, Southern JM, Connon SJ, Kelly VP, The human tRNA-guanine transglycosylase displays promiscuous nucleobase preference but strict tRNA specificity., Nucleic acids research, 2021 Journal Article, 2021

Mashael A. Alqasem,a Claire Fergus,a J. Mike Southern, *b Stephen J. Connon *b and Vincent P. Kelly, The eukaryotic tRNA-guanine transglycosylase enzyme inserts queuine into tRNA via a sequential bi-bi mechanism, Chemical communications, 56, 2020, p3915 - 3918 Journal Article, 2020 URL

Hayes P., Fergus C., Ghanim M., Cirzi C., Burtnyak L., McGrenaghan C.J., Tuorto F., Nolan D.P., Kelly V.P., Queuine micronutrient deficiency promotes warburg metabolism and reversal of the mitochondrial ATP synthase in hela cells, Nutrients, 12, (3), 2020 Journal Article, 2020 DOI

A. Prasanth Saraswati,+ Nicola Relitti,+ Margherita Brindisi,+ Jeremy D. Osko, Giulia Chemi, 4 Stefano Federico, Alessandro Grillo, Simone Brogi, Niamh H. McCabe, Richard C. Turkington, 5 Ola Ibrahim, Jeffrey O'Sullivan, Stefania Lamponi, Magda Ghanim, Vincent P. Kelly, Daniela Zisterer, 6 Rebecca Amet, Patricia Hannon, Francesca Vanni, Cristina Ulivieri, Daniel Herp, Federica Sarno, 7 Antonella Di Costanzo, Fulvio Saccoccia, Giovina Ruberti, Manfred Jung, Lucia Altucci, Sandra Gemma, 8 Stefania Butini, David W. Christianson, and Giuseppe Campiani, Spiroindoline-Capped Selective HDAC6 Inhibitors: Design, 2 Synthesis, Structural Analysis, and Biological Evaluation , ACS Medicinal Chemistry Letters, 2020 Journal Article, 2020 TARA - Full Text URL

Chang Y.-H., Nishimura S., Oishi H., Kelly V.P., Kuno A., Takahashi S., TRMT2A is a novel cell cycle regulator that suppresses cell proliferation, Biochemical and Biophysical Research Communications, 508, (2), 2019, p410 - 415, p410-415 Journal Article, 2019 DOI

Galván-Peña, S., Carroll, R.G., Newman, C., (...), Modis, L.K., O'Neill, L.A., Malonylation of GAPDH is an inflammatory signal in macrophages, Nature Communications, 10, (1), 2019, p338- Journal Article, 2019 TARA - Full Text URL

Müller M, Legrand C, Tuorto F, Kelly VP, Atlasi Y, Lyko F, Ehrenhofer-Murray AE., Queuine links translational control in eukaryotes to a micronutrient from bacteria., Nucleic acids research, 2019 Journal Article, 2019 DOI

Browning J, Rooney M, Hams E, Takahashi S, Mizuno S, Sugiyama F, Fallon PG, Kelly VP., Highly efficient CRISPR-targeting of the murine Hipp11 intergenic region supports inducible human transgene expression., Molecular biology reports, 2019 Journal Article, 2019 DOI

Jantsch, M.F., Quattrone, A., O'Connell, M., (...), Ule, J., Fray, R., Positioning Europe for the EPITRANSCRIPTOMICS challenge, RNA Biology, 2018, p1-3 Journal Article, 2018

Rooney M.F., Hill E.W., Kelly V.P., Porter R.K., The "speed gene" effect of myostatin arises in Thoroughbred horses due to a promoter proximal SINE insertion, PLoS ONE, 13, (10), 2018 Journal Article, 2018 DOI

Saitoh S, Okano S, Nohara H, Nakano H, Shirasawa N, Naito A, Yamamoto M, Kelly VP, Takahashi K, Tanaka T, Nakajima M, Nakajima O., 5-aminolevulinic acid (ALA) deficiency causes impaired glucose tolerance and insulin resistance coincident with an attenuation of mitochondrial function in aged mice., PLoS One, 13, (1), 2018, p0189593- Journal Article, 2018 DOI TARA - Full Text

Varghese S, Cotter M, Chevot F, Fergus C, Cunningham C, Mills KH, Connon SJ, Southern JM, Kelly VP., In vivo modification of tRNA with an artificial nucleobase leads to full disease remission in an animal model of multiple sclerosis., Nucleic Acids Research, 45, (4), 2017, p2029-2039 Journal Article, 2017 DOI

Williams JM, Bezak T, Das M, Ning Z, Lucking EF, Kelly VP, Harrison P, Young P, O'Connell MJ, Dockery P, O'Halloran KD, Moore T , Psg22 null mouse embryos develop normally under normoxic and hypoxic conditions of pregnancy., Science Matters, 10, (19185), 2016 Journal Article, 2016 DOI URL

Fergus, C., Barnes, D., Alqasem, M.A., Kelly, V.P, The queuine micronutrient: Charting a course from microbe to man , Nutrients, 7, (4), 2015, p2897-2929 Journal Article, 2015 DOI

Tannahill, GM, Curtis, AM, Adamik, J, Palsson-McDermott, EM, McGettrick, AF, Goel, G, Frezza, C, Bernard, NJ, Kelly, B, Foley, NH, Zheng, L, Gardet, A, Tong, Z, Jany, SS, Corr, SC, Haneklaus, M, Caffrey, BE, Pierce, K, Walmsley, S, Beasley, FC, Cummins, E, Nizet, V, Whyte, M, Taylor, CT, Lin, H, Masters, SL, Gottlieb, E, Kelly, VP, Clish, C, Auron, PE, Xavier, RJ, O'Neill, LAJ, Succinate is an inflammatory signal that induces IL-1 beta through HIF-1 alpha, NATURE, 496, (7444), 2013, p238-+ Journal Article, 2013 TARA - Full Text DOI

Enhancing the Teaching and Learning of Labortatory Sciences through a Virtual Learning Environment. in, editor(s)Marcus-Quinn A, Bruen C, Allen M, Dundon A, Diggins Y , The Digital Learning Revolution in Ireland : Case Studies from the National Learning Resources Service. , Cambridge, UK, Cambridge Scholars Publishing,, 2012, pp181 - 194, [Robinson GA, Nic A' Bháird N, Kelly VP] Book Chapter, 2012

Kawatani Y, Suzuki T, Shimizu R, Kelly VP, Yamamoto M., Nrf2 and selenoproteins are essential for maintaining oxidative homeostasis in erythrocytes and protecting against hemolytic anemia., Blood, 20, (1), 2011, p986 - 996 Journal Article, 2011

Rakovich T, Boland C, Bernstein I, Chikwana VM, Iwata-Reuyl D, Kelly VP, Queuosine deficiency in eukaryotes compromises tyrosine production through increased tetrahydrobiopterin oxidation., The Journal of Biological Chemistry, 286, (22), 2011, p19354-19363 Journal Article, 2011 DOI URL TARA - Full Text

Rakovich A, Savateeva D, Rakovich T, Donegan JF, Rakovich YP, Kelly VP, Lesnyak V, Eychmuller A , CdTe Quantum Dot/Dye Hybrid System as Photosensitizer for Photodynamic Therapy, Nanoscale Research Letters, 1931, 2010, p7573 - 7585 Journal Article, 2010 DOI

MacLeod AK, Kelly VP, Higgins LG, Kelleher MO, Price SA, Bigley AL, Betton GR, Hayes JD., Expression and localization of rat aldo-keto reductases and induction of the 1B13 and 1D2 isoforms by phenolic antioxidants., Drug Metabolism & Disposition, 38, (2), 2010, p341 - 346 Journal Article, 2010 DOI

Chen Yi-C, Kelly VP, Stachura SV, Garcia GA. , Characterization of the human tRNA-guanine transglycosylase: confirmation of the heteromeric subunit structure, RNA, 16, (5), 2010, p958-968 Journal Article, 2010 DOI

Rakovich A, Rakovich T, Kelly VP, Lesnyak V, Eychmüller A, Rakovich YP, Donegan JF, Photosensitizer methylene blue-semiconductor nanocrystals hybrid system for photodynamic therapy., Journal of nanoscience and nanotechnology, 10, (4), 2010, p2656-2662 Journal Article, 2010 DOI

Boland C, Hayes PA, Santa-Maria I, Nishimura S and Kelly VP, Queuosine formation in eukaryotic tRNA occurs via a mitochondrial localized heteromeric transglycoslase. , Journal of Biological Chemistry, 284, (27), 2009, p18218-18227 Journal Article, 2009 TARA - Full Text DOI

Suzuki T, Kelly VP, Motohashi H, Nakajima O, Takahashi S, Nishimura S, Yamamoto M, Deletion of the selenocysteine tRNA gene in macrophages and liver results in compensatory gene induction of cytoprotective enzymes by Nrf2., Journal of Biological Chemistry, 283, (4), 2008, p2021-2030 Journal Article, 2008 DOI

Arai T, Kelly VP, Minowa O, Noda T, Nishimura S. , The study using wild-type and Ogg1 knockout mice exposed to potassium bromate shows no tumor induction despite an extensive accumulation of 8-hydroxyguanine in kidney DNA , Toxicology , 221, 2006, p179 - 186 Journal Article, 2006 DOI

Kobayashi T, Sakamoto K, Takimura T, Sekine R, Kelly VP, Kamata K, Nishimura S, Yokoyama S., Structural basis of nonnatural amino acid recognition by an engineered aminoacyl-tRNA synthetase for genetic code expansion, Proceedings of the National Academy of Sciences of the United States of America, 102, (5), 2005, p1366 - 1371 Journal Article, 2005 DOI

Kobayashi T, Takimura T, Sekine R, Kelly VP, Kamata K, Sakamoto K, Nishimura S, Yokoyama S., Structural snapshots of the KMSKS loop rearrangement for amino acid activation by bacterial tyrosyl-tRNA synthetase, J. Mol. Biol., 346, (1), 2005, p105 - 117 Journal Article, 2005 DOI

Kelly VP, Takafumi S, Nakajima O, Arai T, Tamai Y, Takahashi S, Nishimura S, Yamamoto M., The distal sequence element of the selenocysteine tRNA gene is a tissue dependant enhancer essential for mouse embryogenesis, Mol. Cell Biol., 25, 2005, p3658 - 3669 Journal Article, 2005 DOI

Itoh K, Mochizuki M, Ishii Y, Ishii T, Shibata T, Kawamoto Y, Kelly VP, Sekizawa K, Uchida K, Yamamoto M., Transcription factor Nrf2 regulates inflammation by mediating the effect of 15-deoxy-prostaglandin J2, Molecular and Cellular Biology, 24, 2004, p36 - 45 Journal Article, 2004 DOI

Aflatoxin Aldehyde Reductases in, editor(s)Penning TM, Petrash JM , Aldo-Keto Reductases and toxicant metabolism, Oxford, UK, Oxford University Press, 2004, pp155 - 170, [Kelly VP, O'Connor T, Ellis EM, Ireland LS, Slattery CM, Sherratt PJ, Crouch DH, Cavin C, Schilter B, Gallina A, Hayes JD] Book Chapter, 2004

Arai T, Kelly VP, Komoro K, Minowa O, Noda T, Nishimura S., Cell proliferation in liver of Mmh/Ogg1-deficient mice enhances mutation frequency because of the presence of 8-hydroxyguanine in DNA, Cancer Research, 63, 2003, p4287 - 4292 Journal Article, 2003 URL

Kelly VP, Sherratt PJ, Crouch DH and Hayes JD, Novel homodimeric and heterodimeric rat gamma-hydroxybutyrate synthases that associate with the Golgi apparatus define a distinct class of aldo-keto reductase 7 family proteins, Biochemical Journal, 366, (3), 2002, p847 - 861 Journal Article, 2002 DOI

Arai T, Kelly VP, Minowa O, Noda T and Nishimura S, High accumulation of oxidative DNA damage, 8-hydroxyguanine, in Mmh/Ogg1 deficient mice by chronic oxidative stress, Carcinogenesis, 23, 2002, p2005 - 2010 Journal Article, 2002 DOI

Grant A, Staffas L, Mancowiz L, Kelly VP, Manson MM, DePierre JW, Hayes JD, Ellis EM, Expression of rat aldehyde reductase AKR7A1: influence of age and sex and tissue-specific inducibility, Biochemal Pharmacology, 62, (11), 2001, p1511 - 1519 Journal Article, 2001 DOI

Kelly VP, Ireland LS, Ellis EM and Hayes JD, Purification from rat liver of a novel constitutively expressed member of the aldo-keto reductase 7 family that is widely distributed in extra-hepatic tissues, Biochemical Journal, 348, (2), 2000, p389 - 400 Journal Article, 2000 DOI

Kelly VP, Ellis EM, Manson MM, Chanas S A, Graeme JM, McLeod R, Neal GE and Hayes JD, Chemoprevention of aflatoxin B1 hepato-carcinogenesis by coumarin, a natural benzopyrone that is a potent inducer of Aflatoxin B1-Aldehyde Reductase, the Glutathione S-Transferase A5 and P1 Subunits and NAD(P)H:Quinone Oxidoreductase in Rat Liver, Cancer Research, 60, (4), 2000, p957 - 969 Journal Article, 2000 URL

Kelly VP, Purification, cloning and characterisation of novel members of the Aldo-Keto Reductase 7 Family, 1999 Thesis, 1999

Kelly VP and O'Neill LA, Sustained activation of NF kappa B and transient I kappa B alpha degradation induced by tumour necrosis factor in 1321N1 human astrocytoma, Biochemical Society Transactions, 23, (4), 1995, p597S - 597S Journal Article, 1995

Non-Peer-Reviewed Publications

Vincent P. Kelly, Queuine-mimetics - hitting the reset button in autoimmunity, European Epitranscriptomics Network, Online (Trento Italy), 21st Sept, 2021, Prof. Alessandro Quattrone Invited Talk, 2021

Vincent P. Kelly, The queuine micronutrient pathway as a therapeutic target in autoimmune disease, Translational Medicine Research Program, The Hospital for Sick Children, Toronto Canada, 14th Jan, 2019, Dr. Colin McKerlie Invited Talk, 2019

Research Expertise

Description

Vitamins, minerals and micronutrients are naturally occurring compounds with essential biological activities. Although their consumption does not provide any direct calorific return, as would be the case for macronutrients i.e. protein, fat, carbohydrate, their deficiency can have a major impact on human health. Understanding the role that such compounds play in human physiology can be greatly assisted through the study of transgenic animals which can be engineered to mirror the disease effects seen in humans. For the past decade, our laboratory has been pursuing a largely unexplored avenue of research, working on the queuine micronutrient. This molecule is made exclusively by bacteria but surprisingly is salvaged by plants and animals, including humans, for largely unknown reasons. Our efforts succeeded in identifying the mechanism that mammals use to obtain queuine from the diet and we have made substantial progress in understanding queuine's physiological role. Part of the attraction of working in the micronutrient field is the breath of physiological effects that these often-overlooked molecules can have in disease and human health. Sir James Black, Scottish physician, pharmacologist and 1988 winner of the Nobel Prize in Physiology and Medicine, once famously stated that "The most fruitful basis for the discovery of a new drug is to start with an old drug". In this vein of thought, our group in collaboration with colleagues in Chemistry, have been developing mimetics of queuine to interrogate the possibility of using such compounds to treat disease. Recently, we have published the first of our findings, showing that queuine mimetics can drastically reverse the clinical disease process (i.e. paralysis and autoimmunity) associated with the animal model of Multiple Sclerosis. Based on these findings, my colleagues and I have co-founded a university spin-out company called Azadyne that is now developing queuine-based therapeutics for the treatment of autoimmune disease. Arguably, above any other aspect of human physiology, the ability to give rise to offspring is paramount. There is now a growing awareness, as highlighted extensively in the media, that fertility in men is dropping drastically in the Western world. Sperm counts have more than halved in the past 40 years and it is estimated that the levels are continuing to fall by an average of 1.4% per year. Although there is no impending threat of human extinction, the impact can be tragic for those couples trying to conceive. Surprisingly, the underlying cause for this drop in fertility remains uncertain. Based on our laboratory's experience in fertility and transgenic technologies (see below) we have ongoing investigations on the use of micronutrients in male infertility, that are based on two commercial projects. Our group also has an ongoing research interest in developing natural anti-cancer agents for the treatment of oral and oesophageal cancer. With over 25 years of experience in transgenic technologies, our research group established the only transgenic facility on the island of Ireland (www.transgenics.ie) a little over 6 years ago. Presently, the transgenic facility offers a range of services including, rederivation, IVF, sperm and egg cryopreservation, dry-shipping and cold-shipping of germplasm and CRISPR/Cas9 gene-editing technology to manipulate the mouse genome. Our transgenic facility has carried out hundreds of vital transgenic tasks for researchers in Trinity College and other universities nationally. As always, we are delighted to discuss new projects and provide advice to researchers on the optimal transgenic methods to address individual research questions.

Keywords

Animal Biotechnology; Animal Reproduction; Embryology; Immunology, Immunotherapy; Nutrition

Recognition

Representations

European Working Group on the creation, breeding, maintenance and reporting of genetically altered animals 26th Jun

Irish representative for the EMMA (European Mouse Mutant Archive), which is a repository and distributor of mutant mouse strains for basic biomedical research. 15th Jun

Lead administrator of the Irish Transgenic Network, which co-ordinates the transgenic activities of HEIs nationally. The group has helped shape national policy for the use of transgenic animals in research. 1st Oct

Awards and Honours

Innovation Awards: Winner 'Inventor' Category 1st Dec 2020

Innovation Awards: Nomiated 'Campus Company Founders' Category 1st Dec 2020

Innovation Awards: Nominated 'Inventor' Category 15th Nov 2019

Memberships

Biochemical Society 1st Oct 2000 – Present date