Dr. Vincent Kelly
Assoc Prof/Academic Co-Ordinator, Biochemistry
Biography
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 10 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.
Publications and Further Research Outputs
Peer-Reviewed Publications
Zhang, Jilei, Zhang, Yongguo, McGrenaghan, Callum J., Kelly, Vincent P., Xia, Yinglin, Sun, Jun, Disruption to tRNA Modification by Queuine Contributes to Inflammatory Bowel Disease, Cellular and Molecular Gastroenterology and Hepatology, 2023
Hung SH, Elliott GI, Ramkumar TR, Burtnyak L, McGrenaghan CJ, Alkuzweny S, Quaiyum S, Iwata-Reuyl D, Pan X, Green BD, Kelly VP, de Crécy-Lagard V, Swairjo MA., Structural basis of Qng1-mediated salvage of the micronutrient queuine from queuosine-5'-monophosphate as the biological substrate., Nucleic acids research, 51, (2), 2023, p935-951
Sake JA, Selo MA, Burtnyak L, Dähnhardt HE, Helbet C, Mairinger S, Langer O, Kelly VP, Ehrhardt C., Knockout of ABCC1 in NCI-H441 cells reveals CF to be a suboptimal substrate to study MRP1 activity in organotypic in vitro models., European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences, 181, 2023, p106364
Vincent P. Kelly, RNA modifications as targets for autoimmunity , RNA Associated Mechanism Conference: In Immunity and Disease, Steamboat Colorado, 28th Aug - 1st Sept , 2022, Uttiya Basa, Vincent Kelly, Nina Papvasilou, Jayantha Chaudhuri
McDonnell, C.M. and Ghanim, M. and Mike Southern, J. and Kelly, V.P. and Connon, S.J., De-novo designed β-lysine derivatives can both augment and diminish the proliferation rates of E. coli through the action of Elongation Factor P, Bioorganic and Medicinal Chemistry Letters, 59, (128545), 2022
Campiani, G., Khan, T., Ulivieri, C., Staiano, L., Papulino, C., Magnano, S., Nathwani, S., Ramunno, A., Lucena-Agell, D., Relitti, N. and Federico, S., Pozzetti, L., Carullo, G., Casagni, A., Brogi, S., Vanni, F., Galatello, P., Ghanim, M., McCabe, N., Lamponi, S., Valoti, M., Ibrahim, O., O'Sullivan, J., Turkington, R., Kelly, V.P., VanWemmel, R., Fernando Díaz, J., Gemma, S., Zisterer, D., Altucci, L., De Matteis, A., Butini, S., Benedetti, R., Design and synthesis of multifunctional microtubule targeting agents endowed with dual pro-apoptotic and anti-autophagic efficacy, European Journal of Medicinal Chemistry, 235, 2022, p114274-
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
Ciara G Doran, Ryoichi Sugisawa, Michael Carty, Fiona Roche, Claire Fergus, Karsten Hokamp, Vincent P Kelly, Andrew G Bowie, CRISPR/Cas9-mediated SARM1 knockout and epitope-tagged mice reveal that SARM1 does not regulate nuclear transcription, but is expressed in macrophages, Journal of Biological Chemistry, 297, (6), 2021
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
Doran, C.G., Sugisawa, R., Carty, M., Roche, F., Fergus, C., Hokamp, K., Kelly, V.P. and Bowie, A.G., Next generation SARM1 knockout and epitope tagged CRISPR-Cas9-generated isogenic mice reveal that SARM1 does not participate in regulating nuclear transcription, despite confirmation of protein expression in macrophages, bioRxiv, 2021
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, 2020
Mashael A. Alqasem, Claire Fergus, J. Mike Southern, Stephen J. Connon 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
A. Prasanth Saraswati, Nicola Relitti, Margherita Brindisi, Jeremy D. Osko, Giulia Chemi, Stefano Federico, Alessandro Grillo, Simone Brogi, Niamh H. McCabe, Richard C. Turkington, Ola Ibrahim, Jeffrey O'Sullivan, Stefania Lamponi, Magda Ghanim, Vincent P. Kelly, Daniela Zisterer, Rebecca Amet, Patricia Hannon, Francesca Vanni, Cristina Ulivieri, Daniel Herp, Federica Sarno, Antonella Di Costanzo, Fulvio Saccoccia, Giovina Ruberti, Manfred Jung, Lucia Altucci, Sandra Gemma, 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
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
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
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-
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
Jantsch, M.F., Quattrone, A., O'Connell, M., (...), Ule, J., Fray, R., Positioning Europe for the EPITRANSCRIPTOMICS challenge, RNA Biology, 2018, p1-3
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
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-
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
John Williams, Tania Bezak, Mrinmoy Das, Zhenfei Ning, Eric Lucking, Vincent Kelly, Patrick Harrison, Paul Young, Mary O'Connell, Peter Dockery, Ken O'Halloran, Tom Moore, Psg22 null mouse embryos develop normally under normoxic and hypoxic conditions of pregnancy , Matters, 2016
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
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
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-+
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]
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
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
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
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
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
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
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
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
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
Kobayashi, T., Takimura, T., Sekine, R., Kelly, V.P., Kamata, K., Sakamoto, K., Nishimura, S., Yokoyama, S., Erratum: Structural snapshots of the KMSKS loop rearrangement for amino acid activation by bacterial tyrosyl-tRNA synthetase (Journal of Molecular Biology (2005) 346 (105-117) DOI: 10.1016/j.jmb.2004.11.034), Journal of Molecular Biology, 354, (3), 2005
Kobayashi, T., Sakamoto, K., Takimura, T., Sekine, R., Kelly, V.P., Kamata, K., Nishimura, S., Yokoyama, S., Erratum: 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 (February 1, 2005) 102, 5 (1366-1371)), Proceedings of the National Academy of Sciences of the United States of America, 102, (29), 2005
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
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
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
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
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]
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
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
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
Grant, A., Staffas, L., Mankowitz, L., Kelly, V.P., Manson, M.M., DePierre, J.W., Hayes, J.D., Ellis, E.M., Erratum: "Expression of rat aldehyde reductase AKR7A1: Influence of age and sex and tissue-specific inducibility" (Biochemical Pharmacology (2001) 62 (1511-1519) PII: S0006295201007717), Biochemical Pharmacology, 64, (2), 2002
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
Kelly, V.P., Ellis, E.M., Manson, M.M., Chanas, S.A., Moffat, G.J., McLeod, R., Judah, D.J., Neal, G.E., Hayes, J.D., Chemoprevention of aflatoxin B
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
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
Kelly VP, Purification, cloning and characterisation of novel members of the Aldo-Keto Reductase 7 Family, 1999
O'Neill, L.A.J., Kelly, V.P., Sustained activation of NF"B and transient I"B" degradation induced by tumour necrosis factor in 1321N1 human astrocytoma, Biochemical Society Transactions, 23, (4), 1995
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
Non-Peer-Reviewed Publications
Vincent P. Kelly, Why CRISPR is revolutionising animal research....and providing to be a regulatory headache, IAT Symposium, Trinity Biomedical Sciences Institute, 24th May 2023, 2023, Sylvia Meaghan, IAT President
Vincent P. Kelly, Queuine-mimetics - hitting the reset button in autoimmunity, European Epitranscriptomics Network, Online (Trento Italy), 21st Sept, 2021, Prof. Alessandro Quattrone
Vincent P. Kelly, RNA at the therapeutic frontier: Autoimmunity, cancer & neurodegeneration, UCC Biochemical Society, University College Cork, 1st Dec, 2021, Dr. Gary Loughran
Vincent P. Kelly, Genome engineering - Better humans.....and a better world?, UCC Technology Conference, University College Cork, 27th Nov, 2021, UCC MRT Society
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
Research Expertise
Recognition
Representations
European Working Group on the creation, breeding, maintenance and reporting of genetically altered animals
Irish representative for the EMMA (European Mouse Mutant Archive), which is a repository and distributor of mutant mouse strains for basic biomedical research.
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.
Awards and Honours
Innovation Awards: Winner 'Inventor' Category
Innovation Awards: Nomiated 'Campus Company Founders' Category
Innovation Awards: Nominated 'Inventor' Category
Memberships
Biochemical Society