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Dr Michaela Serpi
Darlithydd mewn Cemeg Feddyginiaethol
- SerpiM5@caerdydd.ac.uk
- +44 29208 75571
- Y Prif Adeilad, Ystafell 1.50, Plas y Parc, Caerdydd, CF10 3AT
Trosolwyg
Rwy'n fferyllydd meddyginiaethol profiadol sydd â chefndir cryf mewn darganfod cyffuriau, gyda mwy nag 20 o bapurau a sawl patent yn yr ardal.
Mae gen i sawl blwyddyn o hyfforddiant ôl-ddoethurol mewn canolfannau Ewropeaidd (Perugia, Copenhagen a Chaerdydd) ac America (Prifysgol De California) sy'n rhagorol ar gyfer ymchwil, lle'r oeddwn i'n cydweithio â sawl cwmni fferyllol (Lunbeck, Bioberica, TSRL, Inhibitex / BMS a NuCana). Yn UDA, rwyf wedi cyfrannu'n weithredol at ysgrifennu grant NIH hynod gystadleuol ar gyfer datblygu analogau niwcleotid gwrthfeirysol ond yng Nghaerdydd yn yr Ysgol Fferylliaeth roeddwn yn PI prosiect oncoleg trosiadol a noddir gan NuCana. Ers mis Hydref 2020 rydw i yn fy apwyntiad darlithydd cyntaf.
Mae gen i arbenigedd mewn cemeg organig, datblygu Perthynas Gweithgaredd Strwythur (SAR), dealltwriaeth o Amsugno, dosbarthu, Metabolaeth, ac Esgynnydd (ADME) ac eiddo fferyllolcokinetig, sy'n nodweddion sylfaenol ar gyfer dylunio cyfansawdd a dewis ymgeiswyr arweiniol. Mae gen i wybodaeth ddofn o sbectrosgopeg LC-MS ac NMR, yr wyf yn ei ddefnyddio ar gyfer nodweddu ac astudio sefydlogrwydd a llwybr metabolig analogau newydd.
Mae fy niddordeb ymchwil yn cwmpasu sawl maes darganfod cyffuriau fel y meysydd gwrthfiraol a gwrth-ganser yn ogystal â chlefydau prin ac ymwrthedd gwrthficrobaidd.
Cyhoeddiad
2023
- Douglas, E. A. et al. 2023. Improved antibacterial activity of 1,3,4-oxadiazole-based compounds that restrict Staphylococcus aureus growth independent of LtaS function. ACS Infectious Diseases 9(11), pp. 2141-2159. (10.1021/acsinfecdis.3c00250)
- Serpi, M. et al. 2023. Synthesis, molecular docking and antibacterial activity of an oxadiazole-based lipoteichoic acid inhibitor and its metabolites. Journal of Molecular Structure 1278, article number: 134977. (10.1016/j.molstruc.2023.134977)
- Cook, S. R., Kirkham, E. D., Best, H., Waller-Evans, H., Serpi, M., Pertusati, F. and Lloyd-Evans, E. 2023. Investigating lysosomal and cellular phenotypes of the lysosomal disorder cystinosis. Presented at: 19th Annual WORLDSymposium™ 2023, Orlando, Florida, 21-26 February 2023, Vol. 138. Vol. 2. Elsevier pp. 28-28., (10.1016/j.ymgme.2022.107061)
2022
- Serpi, M., Ferrari, V., McGuigan, C., Ghazaly, E. and Pepper, C. 2022. Synthesis and characterization of nuc-7738, an aryloxy phosphoramidate of 3?-deoxyadenosine, as a potential anticancer agent. Journal of Medicinal Chemistry 65(23), pp. 15789-15804. (10.1021/acs.jmedchem.2c01348)
2021
- Schwenzer, H. et al. 2021. The novel nucleoside analogue ProTide NUC-7738 overcomes cancer resistance mechanisms in vitro and in a first-in-human Phase 1 clinical trial. Clinical Cancer Research 27(23), pp. 6500-6513. (10.1158/1078-0432.CCR-21-1652)
- Slusarczyk, M., Serpi, M., Ghazaly, E., Kariuki, B. M., McGuigan, C. and Pepper, C. 2021. Single diastereomers of the clinical anticancer ProTide agents NUC-1031 and NUC-3373 preferentially target cancer stem cells in vitro. Journal of Medicinal Chemistry 64(12), pp. 8179-8193. (10.1021/acs.jmedchem.0c02194)
- Griffith, H., Serpi, M., Slusarczyk, M. and McGuigan, C. 2021. Phosphoramidate nucleoside derivatives as anticancer agents. WO2017207986A1; US20210130387A1 [Patent].
- Vanden Avond, M. A. et al. 2021. The nucleotide prodrug CERC‐913 improves mtDNA content in primary hepatocytes from DGUOK‐deficient rats. Journal of Inherited Metabolic Disease 44(2), pp. 492-501. (10.1002/jimd.12354)
- Serpi, M. and Pertusati, F. 2021. An overview of ProTide technology and its implications to drug discovery. Expert Opinion on Drug Discovery 16(10), pp. 1149--1161. (10.1080/17460441.2021.1922385)
2020
- Pertusati, F. et al. 2020. Drug repurposing: phosphate prodrugs of anticancer and antiviral FDA-approved nucleosides as novel antimicrobials. Journal of Antimicrobial Chemotherapy 75(10), pp. 2864-2878. (10.1093/jac/dkaa268)
2019
- Morozzi, C. et al. 2019. Targeting GNE myopathy: A dual prodrug approach for the delivery of N-acetylmannosamine 6-phosphate. Journal of Medicinal Chemistry 62(17), pp. 8178-8193. (10.1021/acs.jmedchem.9b00833)
2018
- Slusarczyk, M., Ferrari, V., Serpi, M., Gonczy, B., Balzarini, J. and McGuigan, C. 2018. Symmetrical diamidates as a class of phosphate prodrugs to deliver the 5'-monophosphate form of anticancer nucleoside analogues. ChemMedChem 13(21), pp. 2305-2316. (10.1002/cmdc.201800504)
- Pileggi, E., Serpi, M. and Pertusati, F. 2018. Preparation of pyrimidine alkenyl acyclic nucleoside phosphonoamidates. Current Protocols in Nucleic Acid Chemistry 74(13-14), article number: e56. (10.1002/cpnc.56)
- Pileggi, E., Serpi, M., Andrei, G., Schols, D., Snoeck, R. and Pertusati, F. 2018. Expedient synthesis and biological evaluation of alkenyl acyclic nucleoside phosphonate prodrugs. Bioorganic and Medicinal Chemistry 26(12), pp. 3596-3609. (10.1016/j.bmc.2018.05.034)
- Slusarczyk, M., Serpi, M. and Pertusati, F. 2018. Phosphoramidates and phosphonamidates (ProTides) with antiviral activity. Antiviral Chemistry and Chemotherapy 26, pp. 1-31. (10.1177/2040206618775243)
2017
- Griffith, H., Serpi, M., Slusarczyk, M. and McGuigan, C. 2017. Adenosine derivatives for use in the treatment of cancer. WO2017207989A1 [Patent].
- Serpi, M., De Biasi, R., Pertusati, F., Slusarczyk, M. and McGuigan, C. 2017. Synthetic approaches for the preparation of phosphoramidate prodrugs of 2’-deoxypseudoisocytidine. ChemistryOpen 6(3), pp. 424-436. (10.1002/open.201700019)
2016
- Marinozzi, M., Pertusati, F. and Serpi, M. 2016. λ5-Phosphorus-Containing α-Diazo Compounds (PCDCs): a valuable tool for accessing phosphorus-functionalized molecules. Chemical Reviews 116(22), pp. 13991-14055. (10.1021/acs.chemrev.6b00373)
- Serpi, M., Ferrari, V. and Pertusati, F. 2016. Nucleosided derived antibiotics to fight microbial drug resistance: New utilities for an established class of drugs?. Journal of Medicinal Chemistry 59(23), pp. 10343-10382. (10.1021/acs.jmedchem.6b00325)
- McGuigan, C. et al. 2016. Anti-flavivirus activity of different tritylated pyrimidine and purine nucleoside analogues. ChemistryOpen 5(3), pp. 227-235. (10.1002/open.201500216)
2015
- Pertusati, F., McGuigan, C. and Serpi, M. 2015. Symmetrical diamidate prodrugs of nucleotide analogues for drug delivery. In: Current Protocols in Nucleic Acid Chemistry. Wiley-Blackwell, pp. 60:15.6.1-15.6.10., (10.1002/0471142700.nc1506s60)
- Ferrari, V., Serpi, M., McGuigan, C. and Pertusati, F. 2015. Chemoselective N-deacetylation of protected nucleosides and nucleotides promoted by the Schwartz's reagent. Nucleosides, Nucleotides & Nucleic Acids 34(11), pp. 799-814. (10.1080/15257770.2015.1075552)
- Ferrari, V. and Serpi, M. 2015. Nucleoside analogs and tuberculosis: new weapons against an old enemy. Future Medicinal Chemistry 7(3), pp. 291-314. (10.4155/fmc.14.166)
- Slusarczyk, M., Serpi, M., Griffith, H., McGuigan, C. and Ferrari, V. 2015. Gemcitabine Prodrugs. WO 2015/198058; GB51857 [Patent].
2014
- McGuigan, C. et al. 2014. ProTides of N-(3-(5-(2'-deoxyuridine))prop-2-ynyl)octanamide as potential anti-tubercular and anti-viral agents. Bioorganic and Medicinal Chemistry 22(9), pp. 2816-2824. (10.1016/j.bmc.2014.02.056)
- Slusarczyk, M., Serpi, M., Griffith, H., McGuigan, C. and Ferrari, V. 2014. Prodrug. IN 2014MU02050 [Patent].
2013
- McGuigan, C. et al. 2013. Design, synthesis and biological evaluation of phosphorodiamidate prodrugs of antiviral and anticancer nucleosides. European Journal of Medicinal Chemistry 70, pp. 326-340. (10.1016/j.ejmech.2013.09.047)
2012
- Serpi, M. et al. 2012. Novel phosphoramidate prodrugs of N-Acetyl-(d)-Glucosamine with antidegenerative activity on bovine and human cartilage explants. Journal of Medicinal Chemistry 55(10), pp. 4629-4639. (10.1021/jm300074y)
2011
- Pertusati, F., Serpi, M. and McGuigan, C. 2011. Medicinal chemistry of nucleoside phosphonate prodrugs for antiviral therapy. Antiviral Chemistry and Chemotherapy 22(5), pp. 181-203. (10.3851/IMP2012)
2010
- Morgan, A. H. et al. 2010. Quantitative assays for esterified oxylipins generated by immune cells. Nature Protocols 5(12), pp. 1919-1931. (10.1038/nprot.2010.162)
2008
- McGuigan, C. et al. 2008. Phosphate prodrugs derived from N-acetylglucosamine have enhanced chondroprotective activity in explant cultures and represent a new lead in antiosteoarthritis drug discovery. Journal of Medicinal Chemistry 51(18), pp. 5807-5812. (10.1021/jm800594c)
Articles
- Douglas, E. A. et al. 2023. Improved antibacterial activity of 1,3,4-oxadiazole-based compounds that restrict Staphylococcus aureus growth independent of LtaS function. ACS Infectious Diseases 9(11), pp. 2141-2159. (10.1021/acsinfecdis.3c00250)
- Serpi, M. et al. 2023. Synthesis, molecular docking and antibacterial activity of an oxadiazole-based lipoteichoic acid inhibitor and its metabolites. Journal of Molecular Structure 1278, article number: 134977. (10.1016/j.molstruc.2023.134977)
- Serpi, M., Ferrari, V., McGuigan, C., Ghazaly, E. and Pepper, C. 2022. Synthesis and characterization of nuc-7738, an aryloxy phosphoramidate of 3?-deoxyadenosine, as a potential anticancer agent. Journal of Medicinal Chemistry 65(23), pp. 15789-15804. (10.1021/acs.jmedchem.2c01348)
- Schwenzer, H. et al. 2021. The novel nucleoside analogue ProTide NUC-7738 overcomes cancer resistance mechanisms in vitro and in a first-in-human Phase 1 clinical trial. Clinical Cancer Research 27(23), pp. 6500-6513. (10.1158/1078-0432.CCR-21-1652)
- Slusarczyk, M., Serpi, M., Ghazaly, E., Kariuki, B. M., McGuigan, C. and Pepper, C. 2021. Single diastereomers of the clinical anticancer ProTide agents NUC-1031 and NUC-3373 preferentially target cancer stem cells in vitro. Journal of Medicinal Chemistry 64(12), pp. 8179-8193. (10.1021/acs.jmedchem.0c02194)
- Vanden Avond, M. A. et al. 2021. The nucleotide prodrug CERC‐913 improves mtDNA content in primary hepatocytes from DGUOK‐deficient rats. Journal of Inherited Metabolic Disease 44(2), pp. 492-501. (10.1002/jimd.12354)
- Serpi, M. and Pertusati, F. 2021. An overview of ProTide technology and its implications to drug discovery. Expert Opinion on Drug Discovery 16(10), pp. 1149--1161. (10.1080/17460441.2021.1922385)
- Pertusati, F. et al. 2020. Drug repurposing: phosphate prodrugs of anticancer and antiviral FDA-approved nucleosides as novel antimicrobials. Journal of Antimicrobial Chemotherapy 75(10), pp. 2864-2878. (10.1093/jac/dkaa268)
- Morozzi, C. et al. 2019. Targeting GNE myopathy: A dual prodrug approach for the delivery of N-acetylmannosamine 6-phosphate. Journal of Medicinal Chemistry 62(17), pp. 8178-8193. (10.1021/acs.jmedchem.9b00833)
- Slusarczyk, M., Ferrari, V., Serpi, M., Gonczy, B., Balzarini, J. and McGuigan, C. 2018. Symmetrical diamidates as a class of phosphate prodrugs to deliver the 5'-monophosphate form of anticancer nucleoside analogues. ChemMedChem 13(21), pp. 2305-2316. (10.1002/cmdc.201800504)
- Pileggi, E., Serpi, M. and Pertusati, F. 2018. Preparation of pyrimidine alkenyl acyclic nucleoside phosphonoamidates. Current Protocols in Nucleic Acid Chemistry 74(13-14), article number: e56. (10.1002/cpnc.56)
- Pileggi, E., Serpi, M., Andrei, G., Schols, D., Snoeck, R. and Pertusati, F. 2018. Expedient synthesis and biological evaluation of alkenyl acyclic nucleoside phosphonate prodrugs. Bioorganic and Medicinal Chemistry 26(12), pp. 3596-3609. (10.1016/j.bmc.2018.05.034)
- Slusarczyk, M., Serpi, M. and Pertusati, F. 2018. Phosphoramidates and phosphonamidates (ProTides) with antiviral activity. Antiviral Chemistry and Chemotherapy 26, pp. 1-31. (10.1177/2040206618775243)
- Serpi, M., De Biasi, R., Pertusati, F., Slusarczyk, M. and McGuigan, C. 2017. Synthetic approaches for the preparation of phosphoramidate prodrugs of 2’-deoxypseudoisocytidine. ChemistryOpen 6(3), pp. 424-436. (10.1002/open.201700019)
- Marinozzi, M., Pertusati, F. and Serpi, M. 2016. λ5-Phosphorus-Containing α-Diazo Compounds (PCDCs): a valuable tool for accessing phosphorus-functionalized molecules. Chemical Reviews 116(22), pp. 13991-14055. (10.1021/acs.chemrev.6b00373)
- Serpi, M., Ferrari, V. and Pertusati, F. 2016. Nucleosided derived antibiotics to fight microbial drug resistance: New utilities for an established class of drugs?. Journal of Medicinal Chemistry 59(23), pp. 10343-10382. (10.1021/acs.jmedchem.6b00325)
- McGuigan, C. et al. 2016. Anti-flavivirus activity of different tritylated pyrimidine and purine nucleoside analogues. ChemistryOpen 5(3), pp. 227-235. (10.1002/open.201500216)
- Ferrari, V., Serpi, M., McGuigan, C. and Pertusati, F. 2015. Chemoselective N-deacetylation of protected nucleosides and nucleotides promoted by the Schwartz's reagent. Nucleosides, Nucleotides & Nucleic Acids 34(11), pp. 799-814. (10.1080/15257770.2015.1075552)
- Ferrari, V. and Serpi, M. 2015. Nucleoside analogs and tuberculosis: new weapons against an old enemy. Future Medicinal Chemistry 7(3), pp. 291-314. (10.4155/fmc.14.166)
- McGuigan, C. et al. 2014. ProTides of N-(3-(5-(2'-deoxyuridine))prop-2-ynyl)octanamide as potential anti-tubercular and anti-viral agents. Bioorganic and Medicinal Chemistry 22(9), pp. 2816-2824. (10.1016/j.bmc.2014.02.056)
- McGuigan, C. et al. 2013. Design, synthesis and biological evaluation of phosphorodiamidate prodrugs of antiviral and anticancer nucleosides. European Journal of Medicinal Chemistry 70, pp. 326-340. (10.1016/j.ejmech.2013.09.047)
- Serpi, M. et al. 2012. Novel phosphoramidate prodrugs of N-Acetyl-(d)-Glucosamine with antidegenerative activity on bovine and human cartilage explants. Journal of Medicinal Chemistry 55(10), pp. 4629-4639. (10.1021/jm300074y)
- Pertusati, F., Serpi, M. and McGuigan, C. 2011. Medicinal chemistry of nucleoside phosphonate prodrugs for antiviral therapy. Antiviral Chemistry and Chemotherapy 22(5), pp. 181-203. (10.3851/IMP2012)
- Morgan, A. H. et al. 2010. Quantitative assays for esterified oxylipins generated by immune cells. Nature Protocols 5(12), pp. 1919-1931. (10.1038/nprot.2010.162)
- McGuigan, C. et al. 2008. Phosphate prodrugs derived from N-acetylglucosamine have enhanced chondroprotective activity in explant cultures and represent a new lead in antiosteoarthritis drug discovery. Journal of Medicinal Chemistry 51(18), pp. 5807-5812. (10.1021/jm800594c)
Book sections
- Pertusati, F., McGuigan, C. and Serpi, M. 2015. Symmetrical diamidate prodrugs of nucleotide analogues for drug delivery. In: Current Protocols in Nucleic Acid Chemistry. Wiley-Blackwell, pp. 60:15.6.1-15.6.10., (10.1002/0471142700.nc1506s60)
Conferences
- Cook, S. R., Kirkham, E. D., Best, H., Waller-Evans, H., Serpi, M., Pertusati, F. and Lloyd-Evans, E. 2023. Investigating lysosomal and cellular phenotypes of the lysosomal disorder cystinosis. Presented at: 19th Annual WORLDSymposium™ 2023, Orlando, Florida, 21-26 February 2023, Vol. 138. Vol. 2. Elsevier pp. 28-28., (10.1016/j.ymgme.2022.107061)
Patents
- Griffith, H., Serpi, M., Slusarczyk, M. and McGuigan, C. 2021. Phosphoramidate nucleoside derivatives as anticancer agents. WO2017207986A1; US20210130387A1 [Patent].
- Griffith, H., Serpi, M., Slusarczyk, M. and McGuigan, C. 2017. Adenosine derivatives for use in the treatment of cancer. WO2017207989A1 [Patent].
- Slusarczyk, M., Serpi, M., Griffith, H., McGuigan, C. and Ferrari, V. 2015. Gemcitabine Prodrugs. WO 2015/198058; GB51857 [Patent].
- Slusarczyk, M., Serpi, M., Griffith, H., McGuigan, C. and Ferrari, V. 2014. Prodrug. IN 2014MU02050 [Patent].
Ymchwil
Gwrthfacterol
Ymhlith bacteria gram-positif sy'n gwrthsefyll cyffuriau, efallai mai Staphylococcus aureus, sy'n gyfrifol am heintiau croen a meinwe meddal a sepsis bacteriol, yw'r pathogen o'r pryder mwyaf. Mae marwolaeth bacteremia S. aureus yn parhau tua 20–40%. Mae S. aureus yn gynyddol wrthsefyll nifer fwy o asiantau gwrthficrobaidd (ee straen sy'n gwrthsefyll methicillin (MRSA)). Mae'r vancomycin gwrthfiotig glycol-peptid yn aml yn cael ei ystyried fel dewis olaf i drin heintiau o'r fath; Fodd bynnag, mae straeniau gyda gwrthiant vancomycin (VRE) eisoes wedi'u hadrodd. Oherwydd yr anhawster cynyddol wrth drin yr heintiau hyn, mae ffyrdd newydd o atal twf S. aureus a mathau eraill o facteria (ee MRSA, C. difficile, Enterococcus faecalis, ac ati) yn cael eu ceisio'n drwm. Ar gyfer hyn rydym yn ymchwilio i foleciwlau cyffuriau bach fel atalyddion posibl synthesis asid Lipoteichoic. Dau ensym yw'r targedau penodol:
1) y synthase asidau lipoteichoic (LtaS), ensym allweddol sy'n ymwneud â synthesis math I LTA synthesis (LTAs), sef glycol-polymerau sy'n gweithredu'r peptidoglycan mewn organebau gram positif. Mae LTAs yn hanfodol ar gyfer twf bacteria gram-positif.
2) ligase protein cludwr D-alanyl (AMP ffurfio) (DltA), sy'n un o'r ensym sy'n ymwneud â swyddogaeth LTA gyda D-alanine. Blocio'r broses D-alanylation, yn arwain mewn llawer o facteria pathogenig i dueddiad uwch i wrthfiotigau cationig ac amddiffynfeydd cynnal cynyddol. Mae diffyg D-alanine hefyd yn diddymu cynhyrchu bioffilm ac yn lleihau pathogenicity y bacteria hyn.
Ariannwyd y gwaith hwn gan wobr drawsddisgyblaethol ymddiriedolaeth Wellcome ISSF3 mewn cydweithrediad â'r Athro David Williams yn yr Ysgol Deintyddiaeth a Dr Ian Fallis yn yr Ysgol Cemeg ym Mhrifysgol Caerdydd. Mae gwobr Hadau GW4 wedi caniatáu ehangu'r cydweithio i Dr Maisem Labei ym Mhrifysgol Caerfaddon, Dr Seana Duggan ym mhrifysgol Bryste a Dr Dhara Malavia a Dr Mark Stappers ym Mhrifysgol Caerwysg. Yr Athro Laura Mae De Luca ym mhrifysgol Messina hefyd yn cefnogi'r prosiect gyda tecniques dylunio cyffuriau â chymorth cyfrifiadur.
Ail-bwrpasu cyffuriau niwcleosid fel gwrthfiotig. Yn benodol, dangoswyd bod analogau niwcleosid a ddefnyddir wrth drin heintiau firaol a chyflyrau canser hefyd yn cael rhywfaint o effaith yn erbyn bacteria. Yn benodol, adroddwyd bod gan nifer o niwcleosidau naturiol a'u analogau a addaswyd yn synthetig weithgaredd gwrthfiotig cymedrol i dda yn erbyn gwahanol straeniau bacteriol a ffwngaidd. Mae'r cyfansoddion hyn yn targedu sawl proses hanfodol o gelloedd bacteriol a ffwngaidd fel metaboledd niwcleosid a wal gell, asid niwclëig, a biosynthesis protein. Felly, mae ganddynt botensial mawr i'w defnyddio fel gwrthfiotigau ar gyfer trin heintiau bacteriol, yn enwedig y rhai a achosir gan straeniau bacteriol aml-wrthsefyll.
Mae angen gwrthfiotigau newydd ar frys i frwydro yn erbyn cynnydd heintiau oherwydd micro-organebau sy'n gwrthsefyll cyffuriau. Ar hyn o bryd rwy'n archwilio potensial hen niwcleosidau a'u analogau newydd i frwydro yn erbyn ymwrthedd gwrthficrobaidd.
Mae'r gwaith hwn ar y cyd â Dr Mandy Wootton, Gwyddonydd Arweiniol yn yr Uned Cemotherapi Gwrthficrobaidd Arbenigol yn Microbioleg Caerdydd a gyda Dr Hans Steenackers o Ganolfan Microbaidd a Phlanhigion Geneteg, Heverlee, Gwlad Belg.
Anhwylderau storio lysosomal
Mae'r rhain yn anhwylderau metabolaidd genetig prin oherwydd diffygion mewn swyddogaethau lysosomal, fel arfer yn amlwg o fabandod gyda rhai plant yn cael problemau meddygol difrifol sy'n peryglu bywyd. Ynghyd â Dr Emyr Lloyd-Evans, biolegydd sy'n arbenigo ar sffinolipid yn Ysgol y Biowyddorau ym Mhrifysgol Caerdydd, rydym yn gweithio i ddatblygu analogau cyfansoddyn naturiol sy'n gallu atal y synthase glwcosylceramide, ensym sy'n ymwneud â chlefyd Gaucher. Ynghyd â Dr Fabrizio Pertusati a Dr Emyr Lloyd-Evans, rydym hefyd yn edrych ar fersiynau newydd o'r cysteamine cyffuriau a'r miglustat, a fydd yn feddyginiaeth fwy effeithiol a mwy diogel ar gyfer trin dau gyflwr prin a geneteg, sy'n peryglu bywyd yn y drefn honno cystinosis a chlefyd Nieman Pick. Mae grant ISSF3 Ymddiriedolaeth Wellcome (49k) yn cefnogi'r ymchwil ar gyfer y cystinosis ar hyn o bryd.
Cynhelir yr ymchwil hon mewn cydweithrediad â Dr Lloyd-Evans yn Ysgol Biowyddoniaeth Caerdydd a Dr Fabrizio Pertusati yn Ysgol Fferylliaeth Caerdydd.
Gwrth-ganser
Mewn cydweithrediad â NuCana, cwmni biofferyllol clinigol, rwy'n defnyddio technoleg ProTide i drawsnewid rhai o'r asiantau cemotherapi a ragnodir fwyaf, analogau niwcleoside, yn feddyginiaethau mwy effeithiol a mwy diogel. Mae asiantau gwrth-ganser math ProTide yn goresgyn y mecanweithiau gwrthiant allweddol sy'n gysylltiedig ag analogau niwcleosid gan wella eu heffeithiolrwydd yn y therapïau canser. Ar wahân i ddatblygu cyffuriau gwrth-ganser newydd, rydym wedi sefydlu rhwydwaith ymchwil gyda'r Athro David Harrison yn Ysgol Meddygaeth Prifysgol St Andrew a'r Athro Chris Pepper yn Ysgol Feddygaeth Brighton a Sussex i ymchwilio i'r mecanwaith biolegol a biocemegol y tu ôl i weithgarwch gwell y prodrugs.
Bywgraffiad
Graddiais mewn Gwyddorau Fferyllol yn 1998 o Brifysgol Talaith Cagliari. Ar ôl hyfforddeiaeth fer yn Rhone Poulenc Rorer yng Nghanolfan Ymchwil Vitry Alfortville ym Mharis (FR) yn 2000 dyfarnwyd Cymrodoriaeth Croeso Glaxo i mi ymuno â grŵp ymchwil yr Athro Roberto Pellicciari ym Mhrifysgol Perugia (yr Eidal) lle cwblheais fy PhD mewn Cemeg Feddyginiaethol yn 2005 gydag ymchwil wedi'i gyfeirio at y maes niwroddirywiol ac mewn cydweithrediad â'r cwmni fferyllol Lundbeck yn Copenhagen (DK). Yn ystod fy PhD dyfarnwyd Cymrodoriaeth Safle Hyfforddi Marie Curie i mi, a roddodd gyfle i mi dreulio chwe mis yn gweithio yn Ysgol Fferylliaeth Frenhinol Denmarc yn Copenhagen (DK). Yn 2005 ymunais â grŵp cemeg feddyginiaethol yr Athro Chris McGuigan ym Mhrifysgol Caerdydd gan weithio tan fis Ionawr 2008 fel ôl-ddoethuriaeth ar gemeg carbohydrad analogau glwcosamine N-acetyl ar gyfer prosiect darganfod cyffuriau osteoarthritis a noddir gan y cwmni fferyllol Bioberica. O fis Ionawr 2008 i fis Ionawr 2011 rwyf wedi gweithio i ddylunio analogau niwcleosid niwcleosid cylchol ar gyfer trin heintiau firaol fel cymrawd ôl-ddoethurol a ariennir gan NIH ym Mhrifysgol Southern California (LA, UDA) yng Ngrŵp yr Athro Charles E. McKenna. Yn 2011 roeddwn yn ôl ym Mhrifysgol Caerdydd yn gweithio fel Cydymaith Ymchwil yn gyntaf ar gyfer prosiect gwrthfeirysol a ariannwyd gan Inhibitex/BMS (2011-2012) ac yna fel Cymrawd Ymchwil ar gyfer rhaglen oncoleg a noddir gan NuCana. Ym mis Hydref 2020 cefais fy mhenodi'n ddarlithydd mewn cemeg feddyginiaethol yn Ysgol Cemeg Prifysgol Caerdydd. Mae fy niddordeb ymchwil yn cwmpasu gwahanol feysydd o ddarganfod cyffuriau megis datblygu asiantau gwrthganser a gwrthficrobaidd, yn ogystal â moleciwlau bach ar gyfer trin clefydau prin.