Dr. Niamh O'Boyle

• Greene TF, Wang S, Greene LM, Nathwani SM, Pollock JK, Malebari AM, McCabe T, Twamley B, O'Boyle NM, Zisterer DM, Meegan MJ, Synthesis and Biochemical Evaluation of 3-Phenoxy-1,4-diarylazetidin-2-ones as Tubulin-Targeting Antitumor Agents., Journal of Medicinal Chemistry, 59, (1), 2016, p90 - 113Journal Article, 2016, DOI , URL , TARA - Full Text
• Meegan MJ, Nathwani S, Twamley B, Zisterer DM, O'Boyle NM., Piperlongumine (piplartine) and analogues: Antiproliferative microtubule-destabilising agents., European Journal of Medicinal Chemistry, 125, 2017, p453 - 463Journal Article, 2017, DOI , TARA - Full Text
• Ann-Therese Karlberg, Kristina Luthman, Krister Holmberg, Niamh O'Boyle, Tamara Delaine, 'Resin compositions', Intellectual Property Office, GB1319110.1, 2013Patent, 2013, URL
• Daniela Zisterer, Mary Meegan, Niamh O'Boyle, Miriam Carr, Lisa Greene and Thomas Greene, 'Combretastatin Derivatives and Uses Therefor', European Patent Office, EP2338877 A1, 2009Patent, 2009, URL
• Malebari, AM, Greene, LM, Nathwani, SM, Fayne, D, O'Boyle, NM, Wang, S, Twamley, B, Zisterer, DM, Meegan, MJ, Beta-lactam analogues of combretastatin A-4 prevent metabolic inactivation by glucuronidation in chemoresistant HT-29 colon cancer cells, European Journal of Medicinal Chemistry, 130, 2017, p261-285Journal Article, 2017, DOI , URL
• O'Boyle, NM, Barrett, I, Greene, LM, Carr, M, Fayne, D, Twamley, B, Knox, AJS, Keely, NO, Zisterer, DM, Meegan, MJ, Lead Optimization of Benzoxepin-Type Selective Estrogen Receptor (ER) Modulators and Downregulators with Subtype-Specific ER-alpha and ER-beta Activity, Journal of Medicinal Chemistry, 61, (2), 2018, p514 - 534Journal Article, 2018, DOI , URL , TARA - Full Text
• Hagvall, L, Niklasson, IB, Rudbäck, J, O'Boyle, NM, Niklasson, E, Luthman, K, Karlberg, A-T, Assessment of cross-reactivity of new less sensitizing epoxy resin monomers in epoxy resin-allergic individuals, Contact Dermatitis, 75, (3), 2016, p144-150Journal Article, 2016, DOI , URL
• Pollock JK, Greene LM, Nathwani SM, Kinsella P, O'Boyle NM, Meegan MJ, Zisterer DM., Involvement of NF-kB in mediating the anti-tumour effects of combretastatins in T cells., Investigational new drugs, 36, (4), 2018, p523-535Journal Article, 2018, DOI
• Wang, S., Malebari, A.M., Greene, T.F., O'Boyle, N.M., Fayne, D., Nathwani, S.M., Twamley, B., McCabe, T., Keely, N.O., Zisterer, D.M. and Meegan, M.J., 3-Vinylazetidin-2-Ones: Synthesis, antiproliferative and tubulin destabilizing activity in MCF-7 and MDA-MB-231 Breast Cancer Cells, Pharmaceuticals, 12, (2), 2019Journal Article, 2019, DOI
• Niamh M. O'Boyle, Gloria Ana, Patrick M. Kelly, Seema M. Nathwani, Sara Noorani, Darren Fayne, Sandra A. Bright, Brendan Twamley, Daniela M. Zisterer, Mary J. Meegan, Synthesis and evaluation of antiproliferative microtubule-destabilising combretastatin A-4 piperazine conjugates, Organic & Biomolecular Chemistry, 17, 2019, p6184 - 6200Journal Article, 2019, DOI , URL
• Mary J. Meegan and Niamh M. O'Boyle, Anticancer Drugs, 1, MDPI, 2019Book, 2019, URL
• Eavan C. McLoughlin and Niamh M. O'Boyle, Colchicine-Binding Site Inhibitors from Chemistry to Clinic: A Review , Pharmaceuticals, 13, (1), 2020Journal Article, 2020, DOI , URL
• Miriam Carr, Andrew J.S. Knox, Daniel K. Nevin, Niamh O'Boyle, Shu Wang, Billy Egan, Thomas McCabe, Brendan Twamley, Daniela M. Zisterer, David G. Lloyd, Mary J. Meegan, Optimisation of Estrogen Receptor Subtype-Selectivity of a 4-Aryl-4H-Chromene Scaffold Previously Identified by Virtual Screening, Bioorganic & Medicinal Chemistry, 28, (5), 2020, p115261-Journal Article, 2020
• Twamley, B., O'Boyle, N.M., Meegan, M.J., Azetidin-2-ones: Structures of antimitotic compounds based on the 1-(3,4,5-trimethoxyphenyl)azetidin-2-one core, Acta Crystallographica Section E: Crystallographic Communications, 76, 2020, p1187 - 1194Journal Article, 2020, DOI , URL
• T. S. Ibrahim, M. M. Hawwas, A. M. Malebari, E. S. Taher, A. M. Omar, N. M. O'Boyle, E. McLoughlin, Z.K. Abdel-Samii, Y. A. M. M. Elshaier, Potent Quinoline-Containing Combretastatin A-4 Analogues: Design, Synthesis, Antiproliferative, and Anti-Tubulin Activity, Pharmaceuticals, 13, (11), 2020, p393-Journal Article, 2020, DOI , URL
• Sophie Knox, Niamh M. O'Boyle, Skin Lipids in Health and Disease: A Review, Chemistry and Physics of Lipids, 236, 2021, p105055Journal Article, 2021, DOI , URL
• Gloria Ana, Patrick M. Kelly, Azizah M. Malebari, Sara Noorani, Seema M. Nathwani, Brendan Twamley, Darren Fayne, Niamh M. O'Boyle, Daniela M. Zisterer, Elisangela Flavia Pimentel, Denise Coutinho Endringer and Mary J. Meegan, Synthesis and Biological Evaluation of 1-(Diarylmethyl)-1H-1,2,4-Triazoles and 1-(Diarylmethyl)-1H-Imidazoles as a Novel Class of Anti-Mitotic Agent for Activity in Breast Cancer, Pharmaceuticals, 14, (2), 2021, p169-Journal Article, 2021, DOI , URL
• Malebari A.M., Wang S., Greene T.F., O'Boyle N.M., Fayne D., Khan M.F., Nathwani S.M., Twamley B., McCabe T., Zisterer D.M., Meegan M.J., Synthesis and antiproliferative evaluation of 3-chloroazetidin-2-ones with antimitotic activity: Heterocyclic bridged analogues of combretastatin A-4, Pharmaceuticals, 14, (11), 2021, part. 1119-Journal Article, 2021, DOI
• O'Boyle, Niamh; Niklasson, Ida; Ponting, David; Ortega, Miguel; Seifert, Tina; Natsch, Andreas; Luthman, Kristina; Karlberg, Ann-Therese, Nature-Derived Epoxy Resins: Synthesis, Allergenicity and Thermosetting Properties of Pinoresinol Diglycidyl Ether, Toxicology and Industrial Health, 38, (5), 2022, p259-269Journal Article, 2022
• Mary J. Meegan and Niamh M. O'Boyle, Anticancer Drugs 2021, MDPI, 2021Book, 2021, URL
• McLoughlin, E.C. and O'Boyle, N.M., Correction: Colchicine-binding site inhibitors from chemistry to clinic: A review. (Pharmaceuticals, (2020)13, 8), Pharmaceuticals, 13, (4), 2020Journal Article, 2020, DOI , URL
• Malebari, A.M. and Fayne, D. and Nathwani, S.M. and O'Connell, F. and Noorani, S. and Twamley, B. and O'Boyle, N.M. and O'Sullivan, J. and Zisterer, D.M. and Meegan, M.J., Beta-Lactams with antiproliferative and antiapoptotic activity in breast and chemoresistant colon cancer cells, European Journal of Medicinal Chemistry, 189, (112050), 2020Journal Article, 2020, DOI , URL
• McLoughlin EC, O'Brien JE, Trujillo C, Meegan MJ, O'Boyle NM., Application of 2D EXSY and qNMR Spectroscopy for Diastereomeric Excess Determination Following Chiral Resolution of Beta-Lactams, ChemistryOpen, 2022, pe202200119Journal Article, 2022, DOI
• Knox S, Hagvall L, Malmberg P, O'Boyle NM., Topical Application of Metal Allergens Induces Changes to Lipid Composition of Human Skin., Frontiers in Toxicology, 4, 2022, p867163Journal Article, 2022, DOI , URL
• Malebari AM, Duffy Morales G, Twamley B, Fayne D, Khan MF, McLoughlin EC, O'Boyle NM, Zisterer DM, Meegan MJ., Synthesis, Characterisation and Mechanism of Action of Anticancer 3-Fluoroazetidin-2-ones., Pharmaceuticals (Basel, Switzerland), 15, (9), 2022, p1044Journal Article, 2022, DOI
• Wang S., Malebari A.M., Greene T.F., Kandwal S., Fayne D., Nathwani S.M., Zisterer D.M., Twamley B., O'Boyle N.M., Meegan M.J., Antiproliferative and Tubulin-Destabilising Effects of 3-(Prop-1-en-2-yl)azetidin-2-Ones and Related Compounds in MCF-7 and MDA-MB-231 Breast Cancer Cells, Pharmaceuticals, 16, (7), 2023, p1000-Journal Article, 2023, DOI , URL
• McLoughlin E.C., Twamley B., O'Brien J.E., Hannon Barroeta P., Zisterer D.M., Meegan M.J., O'Boyle N.M., Synthesis by diastereomeric resolution, biochemical evaluation and molecular modelling of chiral 3-hydroxyl b-lactam microtubule-targeting agents for the treatment of triple negative breast and chemoresistant colorectal cancers, Bioorganic Chemistry, 141, 2023Journal Article, 2023, DOI , URL
• Byrne A.J., Bright S.A., McKeown J.P., Bergin A., Twamley B., McElligott A.M., Noorani S., Kandwal S., Fayne D., O'Boyle N.M., Williams D.C., Meegan M.J., Synthesis and Pro-Apoptotic Effects of Nitrovinylanthracenes and Related Compounds in Chronic Lymphocytic Leukaemia (CLL) and Burkitt's Lymphoma (BL), Molecules, 28, (24), 2023Journal Article, 2023, DOI
• McVicker RU, O'Boyle NM., Chirality of New Drug Approvals (2013-2022): Trends and Perspectives., Journal of Medicinal Chemistry, 67, (4), 2024, p2305-2320Journal Article, 2024, DOI , URL
• McLoughlin EC, Twamley B, O'Boyle NM., Candida antarctica Lipase B mediated kinetic resolution: A sustainable method for chiral synthesis of antiproliferative ß-lactams., European Journal of Medicinal Chemistry, 276, 2024, p116692Journal Article, 2024, DOI , URL
• O'Boyle, NM, Greene, LM, Bergin, O, Fichet, JB, McCabe, T, Lloyd, DG, Zisterer, DM, Meegan, MJ, Synthesis, evaluation and structural studies of antiproliferative tubulin-targeting azetidin-2-ones, Bioorganic & Medicinal Chemistry, 19, (7), 2011, p2306-2325Journal Article, 2011, DOI , URL , TARA - Full Text
• O'Boyle, NM, Carr, M, Greene, LM, Keely, NO, Knox, AJS, McCabe, T, Lloyd, DG, Zisterer, DM, Meegan, MJ, Synthesis, Biochemical and Molecular Modelling Studies of Antiproliferative Azetidinones causing Microtubule Disruption and Mitotic Catastrophe, European Journal of Medicinal Chemistry, 46, (9), 2011, p4595 - 4607Journal Article, 2011, DOI , URL , TARA - Full Text
• O'Boyle, N.M., Knox, A.J.S., Price, T.P., Williams, D.C., Zisterer, D.M., Lloyd, D.G., Meegan, M.J., Lead identification of beta-lactam and related imine inhibitors of the molecular chaperone heat shock protein 90, Bioorganic & Medicinal Chemistry, 19, (20), 2011, p6055-6068Journal Article, 2011, DOI , URL , TARA - Full Text
• O'Boyle NM, Carr M, Greene LM, Bergin O, Nathwani SM, McCabe T, Lloyd DG, Zisterer DM, Meegan MJ, Synthesis and evaluation of azetidinone analogues of combretastatin A-4 as tubulin targeting agents, Journal of Medicinal Chemistry, 53, (24), 2010, p8569-8584Journal Article, 2010, DOI , URL , TARA - Full Text
• O'Boyle, NM, Greene, LM, Keely, NO, Wang, S, Cotter, TS, Zisterer, DM, Meegan, MJ, Synthesis and biochemical activities of antiproliferative amino acid and phosphate derivatives of microtubule-disrupting beta-lactam combretastatins, EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 62, 2013, p705-721Journal Article, 2013, DOI
• Nathwani, S. M., Hughes, L., Greene, L. M., Carr, M., O'Boyle, N. M., McDonnell, S., Meegan, M. J., Zisterer, D. M., Novel cis-restricted beta-lactam combretastatin A-4 analogues display anti-vascular and anti-metastatic properties in vitro,, Oncol Rep, 29, (2), 2013, p585 - 594Journal Article, 2013
• O'Boyle, NM, Pollock, JK, Carr, M, Knox, AJS, Nathwani, SM, Wang, S, Caboni, L, Zisterer, DM, Meegan, MJ, Beta-Lactam Estrogen Receptor Antagonists and a Dual-Targeting Estrogen Receptor/Tubulin Ligand, Journal of Medicinal Chemistry, 57, (22), 2014, p9370 - 9382Journal Article, 2014, DOI , URL , TARA - Full Text
• O'Boyle, NM, Niklasson, IB, Tehrani-Bagha,AR, Delaine, T, Holmberg, K, Luthman, K, Karlberg, AT, Epoxy resin monomers with reduced skin sensitizing potency, Chemical Research in Toxicology, 27, (6), 2014, p1002-1010Journal Article, 2014, DOI , TARA - Full Text
• Pollock, JK, Verma,NK, O'Boyle, NM, Carr, MG, Meegan, MJ, Zisterer, DM, Combretastatin (CA)-4 and its novel analogue CA-432 impair T-cell migration through the Rho/ROCK signalling pathway, Biochemical Pharmacology, 92, (4), 2014, p544-557Journal Article, 2014, DOI
• Greene, LM, Wang, S, O'Boyle, NM, Bright, SA, Reid, JEA, Kelly, PJ, Meegan, MJ, Zisterer, DM, Combretazet-3 a novel synthetic cis-stable combretastatin A-4-azetidinone hybrid with enhanced stability and therapeutic efficacy in colon cancer, Oncology Reports, 29, (6), 2013, p2451-2458Journal Article, 2013, DOI
• O'Boyle, NM, Delaine, T, Luthman, K, Natsch, A, Karlberg, AT, Analogues of the epoxy resin monomer diglycidyl ether of bisphenol F: Effects on contact allergenic potency and cytotoxicity, Chemical Research in Toxicology, 25, (11), 2012, p2469-2478Journal Article, 2012, DOI , TARA - Full Text
• Greene, LM, O'Boyle, NM, Nolan, DP, Meegan, MJ, Zisterer, DM, The vascular targeting agent Combretastatin-A4 directly induces autophagy in adenocarcinoma-derived colon cancer cells, Biochemical Pharmacology, 84, (5), 2012, p612-624Journal Article, 2012, DOI
• O'Boyle, NM, Meegan, MJ, Designed multiple ligands for cancer therapy, Current Medicinal Chemistry, 18, (31), 2011, p4722-4737Journal Article, 2011, DOI
• Yang,Y., Carta,G., Peters, M.B., Price, T.T., O'Boyle, N.M., Knox, A.J.S., Fayne, D., Williams, D.C., Meegan, M.J., Lloyd, D.G., 'TieredScreen' - Layered virtual screening tool for the identification of novel estrogen receptor alpha modulators, Molecular Informatics, 29, (5), 2010, p421-430Journal Article, 2010, DOI
• Barrett, I., Carr, M.G., O'Boyle, N.M., Greene, L.M., Knox, A., Lloyd, D.G., Zisterer, D.M., Meegan, M.J., Lead identification of conformationally restricted benzoxepin type combretastatin analogs: Synthesis, antiproliferative activity, and tubulin effects, Journal of Enzyme Inhibition and Medicinal Chemistry, 25, (2), 2010, p180-194Journal Article, 2010, DOI
• Greene,. L.M., Nathwani, S.M., Bright, S.A., Fayne, D., Croke, A., Gagliardi,M., McElligott, A.M., O'Connor, L.M., Carr, M.G., Keely, N.O., O'Boyle, N.M., Carroll, P.V., Sarkadi, B., Conneally, E.C., Lloyd,D.G., Lawler, M.P., Meegan, M.J., Zisterer, D.M., The vascular targeting agent combretastatin-A4 and a novel cis-restricted beta-lactam analogue, CA-432, induce apoptosis in human chronic myeloid leukemia cells and ex vivo patient samples including those displaying multidrug resistance, Journal of Pharmacology and Experimental Therapeutics, 335, (2), 2010, p302-313Journal Article, 2010, DOI

• Niamh M. O'Boyle, Daniela M. Zisterer, Mary J. Meegan, Lead Optimization of Benzoxepin-Type Selective Estrogen Receptor (ER) Modulators and Downregulators with Subtype-Specific ERalpha and ERbeta Activity, Proceedings of the 3rd Int. Electron. Conf. Med. Chem., 3rd International Electronic Conference on Medicinal Chemistry, November 2017, edited by Annie Mayence and Jean Jacques Vanden Eynde , 11, (1), Pharmaceuticals, 2017, pp18-Conference Paper, DOI , URL
• Niamh M. O'Boyle, Daniela M. Zisterer, Mary J. Meegan, Microtubule-Destabilising Actions of Piperlongumine and Analogues, Proceedings of the 3rd Int. Electron. Conf. Med. Chem., 3rd International Electronic Conference on Medicinal Chemistry, November 2017, edited by Annie Mayence and Jean Jacques Vanden Eynde , 11, (1), Pharmaceuticals, 2017, pp18-Conference Paper, DOI , URL
• James Patrick Mc Keown, Clara Charleton, Keith Ferris, Sara Noorani, Niamh M O'Boyle, Mary J Meegan, Ethanoanthracenes: Potential chemotherapeutics for chronic lymphocytic leukaemia (CLL), 4th International Electronic Conference on Medicinal Chemistry, Online at www.sciforum.net/conference/ecmc-4, November 2018, edited by MDPI , 2018Poster, DOI , URL
• Eavan Ciara McLoughlin, Mary Meegan, Niamh O'Boyle, Stories from Staudinger: Synthesis of chiral beta-lactams, 5th International Electronic Conference on Medicinal Chemistry, Online at https://sciforum.net/conference/ECMC2019, November 2019, 2019Poster, DOI , URL
• Niamh O'Boyle, Benzoxepin-Type Selective Estrogen Receptor (ER) Modulators and Downregulators with Subtype-Specific ERalpha and ERbeta Activity, 26th Annual GP2A Medicinal Chemistry Conference & 32nd Journées Franco-Belges de Pharmacochimie, Asnelles sur Mer, Normandie, France, 13th June 2018, 2018, GP2AInvited Talk, DOI , URL , TARA - Full Text
• Niamh O'Boyle, Epoxy Resins: From Chemistry to Clinic, Occupational and Environmental Exposure of the Skin to Chemicals, Dublin, 16 - 18 Sept. 2019, 2019Oral Presentation, URL , TARA - Full Text
• Niamh O'Boyle, Organic chemistry practicals: introduction of pre-laboratory assessments for first year pharmacy students, Irish Variety in Chemistry Education 2019, Dublin Institute of Technology, Kevin Street, 26th April 2019, edited by Claire McDonnell , 2019Oral Presentation, URL
• Niamh O'Boyle, Designing a capacity plan for the Aseptic Compounding Unit in St. James's Hospital, Irish Pharmacy Journal , 85, 2007, p303 - 306Journal Article, URL
• Eavan C. McLoughlin, Niamh M. O'Boyle, Combretazets: Enantiomeric Beta-Lactams for the Treatment of Breast Cancer, 6th International Electronic Conference on Medicinal Chemistry, 01-30 November 2020, edited by Dr. Jean Jacques Vanden Eynde , MDPI, 2020Oral Presentation, DOI , URL
• Niamh O'Boyle, Probing the Skin with ToF-SIMS: do Metal Allergens Change Lipid Composition?, 29th Meeting of the European Research Group on Experimental Contact Dermatitis, Online, 3rd February, 2021Invited Talk
• Helesbeux J.-J., Carro L., McCarthy F.O., Moreira V.M., Giuntini F., O'Boyle N.M., Matthews S.E., Bayraktar G., Bertrand S., Rochais C., Marchand P., 29th Annual GP2A Medicinal Chemistry Conference, Pharmaceuticals, 14, (12), 2021, part. 1278Journal Article, DOI
• Eavan C. McLoughlin, Nithya Valupadasu, Niamh M. O'Boyle, A phosphate prodrug of pyrazinib: Improved solubility and antiproliferative activity, 7th International Electronic Conference on Medicinal Chemistry, November 2021, edited by Jean Jacques Vanden Eynde , 2021Poster, DOI , URL
• Mary J. Meegan and Niamh M. O'Boyle, Special Issue 'Anticancer Drugs 2021', Pharmaceuticals, 15, (4), 2022, p479-Journal Article, DOI , URL
• Niamh M. O'Boyle, Targeting Tubulin - a Tale of the Development of the Combretazets, SCF 29th Young Research Fellows Meeting, Nantes, 4-6 July 2022, 2022, Société de Chimie ThérapeutiqueInvited Talk, URL , TARA - Full Text
• Niamh M. O'Boyle, FS-44: Nature-Inspired Epoxy Resins: PinoDGE, Contact Dermatitis, European Society for Contact Dermatitis 15th Congress, Amsterdam, 8-10 June 2022, 86, (S1), Wiley, 2022, pp20-Oral Presentation, URL , TARA - Full Text
• Niamh M. O'Boyle, FC-48: Probing the skin with ToF-SIMS: skin lipid composition upon exposure to metal allergens, Contact Dermatitis, European Society for Contact Dermatitis 15th Congress, Amsterdam, 8-10 July 2022, 86, (S1), Wiley, 2022, pp54 - 55Oral Presentation, DOI , URL , TARA - Full Text
• Alina Qaisar, Jacintha O'Sullivan, Niamh M. O'Boyle, P22: Synthesis and Physicochemical Properties of Amino Acid Prodrugs of the Radiosensitser Pyrazinib, 30th Annual GP2A Medicinal Chemistry Conference, Dublin, 24-26 August 2022, 2022Poster
• Eavan C. McLoughlin, Patricia Hannon Barroeta, Daniela M. Zisterer, and Niamh M. O'Boyle, P41: A comparison of chiral diastereomeric versus kinetic enzymatic resolution for enantioseparation of microtubule depolymerising beta-lactams, 30th Annual GP2A Medicinal Chemistry Conference, Dublin, 24-26 August 2022, 2022Poster
• Niamh O'Boyle(ed.), 30th Annual GP2A Medicinal Chemistry Conference, Pharmaceuticals, Trinity College Dublin, Ireland, 16, (3), 24-26th August 2022, 2023, 432-Proceedings of a Conference, DOI , URL
• Eavan C. McLoughlin , Niamh M. O'Boyle, A biocatalytic approach for kinetic resolution toward enantiopure anti-cancer beta-lactams using Candida antarctica Lipase B, 9th International Electronic Conference on Medicinal Chemistry, 1-30 November 2023, edited by Alfredo Berzal-Herranz , 2023Poster, DOI , URL

I lead a research group that is at the forefront of two fields: developing treatments for drug-resistant cancers and discovering mechanisms of skin allergy. These may seem unconnected, but both are concerned with the intricate interactions between chemicals and the human body. In the inflammation strand of my research, I am elucidating the reasons that certain chemicals cause skin allergy. This had led to a completely new research area: the characterisation of the effects of chemicals on skin lipids. The key direction of this research is improving the understanding of the molecular mechanisms of skin allergy, leading to improved diagnostics and treatments. In the cancer strand of my research, I am developing treatments for multi-drug resistant breast and colon cancers. I consistently publish international peer-reviewed articles, and I have also co-edited two books and am a co-inventor on two patents. My work has been cited over 1200 times and my h-index is 20 (source: Google Scholar, August 2023). I consistently publish in leading journals (e.g. J.Med.Chem and Chem.Res.Toxicol.). My 2020 review article in Pharmaceuticals was awarded 'Highly Cited Paper 2020' and 'Editor's Choice Article' with 180 citations to date. I have been a keynote speaker at several national and international conferences. Since my appointment to TCD, my research has been supported by the Irish Research Council, CAMS-UK, Wellcome Trust, Enterprise Ireland (three grants), Royal Society of Chemistry (three grants), H2020-MSCA-RISE, Panoz Pharmaceutical Innovation PhD scholarships (two grants), and Trinity College (Trinity Research Boost, Provost's PhD Project Award and Dean of Health Sciences Award). I have leveraged over €0.5 million in funding as PI (€1.5 million funding when collaborative grants are included). I am a member of several COST actions including STRATAGEM and EpiLipidNet and have strategic collaborations nationally and internationally. I'm also involved in teaching within PANDORA: the Pan-European Educational Platform on Multidrug Resistant Tumours and Personalised Cancer Treatment, funded by COST Innovators Grant.

• Title

  Can the stress response to reactive oxygen species in tumours be exploited to give a new class of anti-cancer drugs? Dual-targeting of the stress response to reactive oxygen species and tubulin by piperlongumine and related analogues
  Summary

  Cancer is a disease that affects thousands of people and their families every year. The aim of cancer research is to understand what happens in the body to cause cancer, enabling us to prevent it or treat it. This project will investigate new ways to treat cancer, using chemicals called 'oxygen free radicals' that are found in tumors. The research will be based on a natural product known as piperlongumine and the effect that it has on the response of cancer cells to oxygen free radicals. Piperlongumine is found in the fruit plant Piper longum ('Long pepper'). It was recently discovered that piperlongumine can selectively kill cancer cells without harming normal, healthly cells. It is thought that this is because piperlongumine raises the levels of reactive oxygen free radicals in cancer cells, which causes them to die. I will investigate if piperlongumine and other related chemicals have additional biochemical effects in cancer cells that contribute to their anti-cancer effects. In particular the research will focus on a protein called tubulin that is extremely important for cell replication, both in cancer cells and healthy cells. The overall, long-term goal of this research is to design new anti-cancer drugs that will selectively kill cancer cells by manipulating oxygen free radicals and tubulin.
  Funding Agency

  Irish Research Council
  Date From

  2014
  Date To

  2016
• Title

  Analysis of Skin Lipids in Contact Allergy by Mass Spectrometry
  Summary
  Funding Agency

  CAMS-UK and Royal Society of Chemistry
  Date From

  August 2020
  Date To

  September 2021
• Title

  Biochemical Evaluation of the 'Combretazets' - Novel and Potent Drugs for Treating Multi-Drug Resistant Cancers
  Summary

  The aim of this project is to evaluate the biochemical effects of novel, enantiomerally pure β-lactams on breast cancer cells. Specific assays will investigate effects on breast cancer cell proliferation, cell cycle, apoptosis and tubulin polymerisation. This will enable us to identify the best drug candidate for progression to pre-clinical experiments, e.g. in vivo assessment.
  Funding Agency

  Wellcome Trust Institutional Strategic Support Fund
• Title

  Hidden sensitizers in skin care - analytical and clinical investigations of culprit skin allergens in propolis and beeswax
  Summary

  We are surrounded by chemicals and we use numerous products on our skin every day. Skin contact allergy is the most common form of human immunotoxicity, prevalent in a quarter of the European population. Skin allergy to ingredients in cosmetics, fragrances and skin care products is widespread. Beeswax and propolis are popular ingredients in cosmetics, often used in high concentrations, and are often mistaken as safe because they are from a natural source. Unfortunately both can cause skin allergy due to the presence of harmful chemicals. The main skin sensitizers in beeswax and propolis have not been identified, although caffeic acid and two ester derivatives have been suggested as potentially problematic. Our preliminary findings show that oxidation mixtures derived from caffeic acid are protein reactive and hence could be skin sensitizers. The aim of this project is to identify the exact toxic allergenic compounds present in beeswax- and propolis-containing products that cause skin allergy. The project incorporates methods from organic chemistry, analytical chemistry, biochemistry, and dermatology to achieve this goal. By identification of the offending allergens we will contribute to improved diagnosis of contact allergy to beeswax and propolis, and provide the knowledge necessary for restriction of exposure to the harmful chemicals. This will ultimately prevent new cases of contact allergy, providing value to patients with skin disease.
  Funding Agency

  British Skin Foundation
  Date From

  2020
  Date To

  2022
• Title

  Investigation of the effects of hormonal cancer therapy on levels of interferon epsilon in cancer cells of female reproductive tract and breast
  Summary

  Breast cancer is the most common cancer amongst Irish women and its incidence is predicted to rise. The most common subtype is estrogen-receptor positive (ER+) breast cancer, comprising nearly four out of every five cases (79%). Long-term (5 years) hormone treatment such as use of tamoxifen and raloxifene has revolutionised the treatment of ER+ breast cancer and improved the lives of millions of women worldwide. Tamoxifen and raloxifene are selective-estrogen receptor modulators (SERMs), modifying the effects of estrogen in female reproductive tissues. They act as antagonists of the ER in some tissues, such as the breast, and agonists in other tissues, e.g. bone. Tamoxifen is the first-line treatment and is also under investigation for the prophylaxis of breast cancer in high-risk women. Unfortunately, long-term use of tamoxifen significantly increases the risk of endometrial cancer whilst raloxifene has a protective effect. The reasons for this are still unclear and there are likely to be a number of contributing factors. Interferon-epsilon (IFNε) is recently discovered type I interferon that is constitutively expressed in the female reproductive tract (FRT), including the endometrium. IFNε expression is under hormonal control and IFNε levels fluctuate depending on the relative concentrations of estrogen and progesterone. Our preliminary data strongly indicates that IFNε also acts as a tumour suppressor in the FRT. We propose that SERMs modify expression levels of IFNε in endometrial and breast cells and tissues. This would contribute to altered immunity in the endometrium, potentially leading to increased risk of developing cancerous cells. Given the current widespread use of tamoxifen and its potential prophylactic use in the future, unravelling the mechanisms leading to tamoxifen-associated endometrial cancer is of paramount importance. Such knowledge could influence patient treatment, cancer strategies and prescribing guidelines in the future.
  Funding Agency

  Trinity St. James's Cancer Institute
  Date From

  2018
  Date To

  2018
• Title

  Development of Novel Anti-Tumour Beta-Lactams for Treatment of Aggressive Breast Cancer
  Summary

  Triple-negative breast cancer (TNBC) is the most aggressive and lethal form of breast cancer. The most successful drugs target three receptors common to most breast cancers (estrogen receptors, progesterone receptors and HER2 receptors). TNBC does not express any of these receptors and, despite many advances in cancer treatment, remains difficult to treat. This project aims to address an unmet clinical need by developing drugs to treat TNBC. With an increasing incidence of cancer and an ageing population, we need to address this problem now to improve future outcomes for the individual and for society. The development of new drugs to treat TNBC will improve quality-of-life for patients and alleviate the economic burden of cancer on society. Tubulin is a protein that is essential for tumour cell replication. Drugs targeting tubulin, e.g. paclitaxel, are used to treat a wide range of cancers and have saved countless lives. Unfortunately drug resistance and side-effects are common, hence development of new drugs is necessary. A large library of anti-tumour β-lactams that interact with tubulin and halt the growth of cancer cells, including TNBC cells, have been developed by our research group. These compounds are amongst the most potent tubulin-targeting agents ever reported. The β-lactams were initially evaluated as a racemic mixture of two isomers known as enantiomers. It is common that one enantiomer of a drug has a better therapeutic profile, although many drugs are still produced as racemates. The next critical step in this project involves chemical synthesis of the enantiomers of our β-lactams. The most biologically active compounds from our series of over 250 analogues have been chosen for synthesis as single enantiomers. Upon completion of synthesis, biological evaluation of their relative potencies in TBNC cells will allow us to determine which has superior activity. The most promising compounds will be progressed for preclinical development to establish a clinical drug candidate with the potential to save lives. The three overall aims of this research project are: 1. Development of efficient methods for chemical synthesis of enantiomerically pure β-lactams. 2. Evaluation of the anti-tumour effects of the β-lactams in breast cancer cells. 3. Development of the best β-lactams as potential clinical drug candidates for treatment of TNBC. The outcomes of the project will be twofold: firstly, advances in the design of novel anti-cancer drugs to treat TNBC and secondly, development of more efficient methods to synthesise enantiomerically pure β-lactams. The methodology developed from the latter can potentially be applied to the synthesis of number of commercially available β-lactam-containing drugs, e.g. ezetimibe.
  Funding Agency

  University of Dublin, Trinity College
  Date From

  September 2018
  Date To

  September 2022
• Title

  From Chemistry to Clinic: Increasing the Solubility and Stability of Promising Drugs for Gastrointestinal Cancers
  Summary

  Successful drugs must overcome many hurdles on their journey to clinical use, and it is essential to have a favourable solubility and stability profile. We aim to improve the solubility and stability of two promising anti-cancer agents, CC12 and pyrazinib, which are under development as adjunct treatments for colorectal cancer and oesophageal adenocarcinoma respectively. Drug development options for the two compounds are limited due to suboptimal physiochemical properties: poor water solubility (CC12 and pyrazinib) and stability (CC12). Extremely poor water solubility limits their options for in vivo testing and delivery to patients. CC12 is unstable and undesired degradation products form in solutions of the drug. This project aims to overcome these limitations by chemical synthesis of stable, water-soluble versions of CC12 and pyrazinib called prodrugs. Prodrugs are compounds with little or no inherent pharmacological activity that are enzymatically converted to the active drug in vivo. Prodrug formation is an excellent option for improving the solubility and stability of drugs. We propose to attach the phosphate ester group to CC12 and pyrazinib to optimise their physiochemical profiles and enable further progression of these promising compounds along the drug delivery pipeline into clinical studies.
  Funding Agency

  University of Dublin, Trinity College
  Date From

  2020
  Date To

  2021
• Title

  Synthesis and Analysis of Chiral Anti-Tumour Beta-Lactams for Treatment of Aggressive Breast Cancer
  Summary

  Tubulin is a protein that is essential for tumour cell replication. Drugs targeting tubulin, e.g. paclitaxel, are used to treat a wide range of cancers and have saved countless lives. Unfortunately drug resistance and side-effects are common, hence development of new drugs is necessary. A large library of anti-tumour β-lactams that interact with tubulin and halt the growth of cancer cells, including TNBC cells, have been developed by our research group. These compounds are amongst the most potent tubulin-targeting agents ever reported. They target the colchicine-binding site of tubulin, which is distinct from the binding sites targeted by clinically used tubulin-targeting drugs (paclitaxel, vinblastine and vincristine), and hence our compounds could be of value in overcoming multidrug resistance caused by binding-site specific mutations. Our previously synthesised β-lactams were evaluated as racemic mixtures. It is common that one enantiomer of a drug has a better therapeutic profile. Building on our extensive work, the next critical step in this project involves chemical synthesis of the enantiomers of our β-lactams and determination of their enantiomeric excess (optical purity) using chiral HPLC. The most biologically active compounds from our series of over 250 analogues have been chosen for synthesis as single enantiomers. Our objective is to determine if one or both enantiomers are responsible for the antiprolifeative effects. This will allow us to progress this enantiomer along the drug development pipeline as a clinical candidate.
  Funding Agency

  Royal Society of Chemistry
  Date From

  2020
  Date To

  2021

Pharmacology and pharmaceutical sciences, Biochemistry and cell biology, Other health sciences, Chemical Sciences, Medical, health and life sciences, Immunology, Cancer,

• Outstanding Reviewer Award, European Journal of Medicinal Chemistry 2017
• Trinity College Dublin Postgraduate Research Studentship 2009
• Pharmaceutical Society of Ireland Young Pharmacist's forum: Best poster presentation 2006
• Trinity College Dublin Provost's PhD Project Award 2018
• CAMS-UK Fellowship 2019
• XVIIIth European Conference of GP2A: Best Presentation 2009
• Irish Cancer Society Oncology Scholars Travel Award 2008
• University of Gothenburg Department of Chemistry Postdoctoral Scholarship 2010 - 2012
• Irish Research Council Government of Ireland Postdoctoral Fellowship 2014 - 2016
• Trinity College Dublin Postgraduate Research Studentship (1252) 2006
• Best Poster Presentation, STRATAGEM WG2 Meeting and International Online Symposium on 'Synthesis and nanodelivery strategies for new therapeutic tools against Multidrug Resistant Tumours' (online) 15-Dec-2020
• Trinity College Dublin Foundation Scholarship 2003

• Member of the European Society for Contact Dermatitis Present
• Associate Member of the Institute of Chemistry of Ireland 2024
• Member of the Irish Association for Cancer Research 2023
• Member of the European Association for Cancer Research 2023
• Fellow of Trinity College Dublin Present
• Fellow of the Institute of Chemistry of Ireland Present
• Member of the Pharmaceutical Society of Ireland Present
• Member of the Royal Society of Chemistry Present

• Royal Society of Chemistry Ireland Regional Steering Group - Early Career Representative 2020 - 2023
• Group for the Promotion of Pharmaceutical chemistry in Academia: committee member 2017 - present
• COST Action CA17104 Stratagem - management committee substitute (Ireland) and working group member 2019
• Journal Reviewer (journals including PNAS, RSC Med.Chem., J.Med.Chem., Eur.J.Med.Chem., ACS Med.Chem.Lett.)
• Royal Irish Academy Physical, Chemical & Mathematical Sciences multidisciplinary committee (member) 2022-2026