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Dr Helen Waller-Evans
- Siarad Cymraeg
Timau a rolau for Helen Waller-Evans
Darlithydd
Ysgol y Biowyddorau
Trosolwyg
Rwy'n ddarlithydd niwrowyddoniaeth yn y Sefydliad Darganfod Meddyginiaethau. Er mwyn datblygu gwell cyffuriau niwrowyddoniaeth, mae angen i ni ddeall yn llawn rolau targedau cyffuriau posibl a'r llwybrau y maent yn ymwneud â nhw. Mae gwaith yn fy labordy yn canolbwyntio ar nodweddu swyddogaeth targedau cyffuriau niwrowyddoniaeth posibl a datblygu profion i asesu effeithiau cyffuriau newydd ar y swyddogaeth hon. Mae gen i ddiddordeb arbennig mewn datblygu therapïau sy'n gweithredu ar broteinau lysosomaidd i'w defnyddio mewn clefydau seiciatrig a niwrolegol.
Cyhoeddiad
2026
- Best, H. et al. 2026. The long and short of it: Distinct natural crystal packing strategies of Cry toxins from Bacillus thuringiensis. Structure 34 (5), pp.704-717.e3. (10.1016/j.str.2026.01.014)
2025
- Kirkham, E. et al., 2025. Lysosomal pH measurements via dual-imaging microscopy. In: Hughes, S. M. and Basak, I. eds. Lysosomes: Methods and Protocols. Vol. 2976, Methods in Molecular Biology New York, New York, USA: , pp.11-24. (10.1007/978-1-0716-4844-5_2)
- Riseley, R. et al., 2025. Unusual reactivity of 2-amino-1H-indole-3-carboxylate esters. ARKIVOC 2025 (5) 202512417. (10.24820/ark.5550190.p012.417)
- Reeks, J. et al., 2025. High throughput cryo-EM provides structural understanding for modulators of the lysosomal ion channel TRPML1. Structure 33 (8), pp.1374-1385. (10.1016/j.str.2025.05.014)
- Best, H. L. et al. 2025. Niemann-Pick C-like endo-lysosomal dysfunction in DHDDS patient cells, a congenital disorder of glycosylation, can be treated with miglustat. International Journal of Molecular Sciences 26 (4) 1471. (10.3390/ijms26041471)
2024
- Cubitt, J. et al. 2024. Beware of N-Benzoyloxybenzamides. Molecules 29 (21) 5143. (10.3390/molecules29215143)
2023
- Best, H. L. et al. 2023. The role of glycoconjugates as receptors for insecticidal proteins. FEMS Microbiology Reviews 47 (4)(10.1093/femsre/fuad026)
- Somogyi, A. et al., 2023. The synthetic TRPML1 agonist ML-SA1 rescues Alzheimer-related alterations of the endosomal-autophagic-lysosomal system. Journal of Cell Science 136 (6) jcs259875. (10.1242/jcs.259875)
- Fenn, G. D. et al. 2023. Development of a novel anthraquinone-derived fluorescent lysosomal probe. Molecular Genetics and Metabolism 138 (2) 107097. (10.1016/j.ymgme.2022.107097)
- Best, H. et al. 2023. The Batten disease associated protein CLN3 is required for the efflux of lysosomal K. Presented at: 19th Annual WORLDSymposium™ 2023 Orlando, Florida 21-26 February 2023. Vol. 138.Vol. 2. Elsevier. , pp.47-47. (10.1016/j.ymgme.2022.107030)
- Best, H. L. et al. 2023. Disease phenotypes present in CLN7 patient fibroblasts are improved following treatment to reduce glycosphingolipid synthesis.. Presented at: 19th Annual WORLDSymposium™ 2023 Orlando, Florida 21-26 February 2023. Vol. 138.Vol. 2. Elsevier. , pp.17. (10.1016/j.ymgme.2022.107029)
- Cook, S. R. et al. 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)
- Davies, M. et al. 2023. Acid ceramidase inhibition as a mechanism to treat lysosomal disorders. Molecular Genetics and Metabolism 138 (2) 107069. (10.1016/j.ymgme.2022.107069)
- Fenn, G. D. , Lloyd-Evans, E. and Waller-Evans, H. 2023. Investigation of cannabidiol as a potential therapeutic in Niemann-Pick disease. Presented at: 19th Annual WORLDSymposium™ 2023 Orlando, Florida 21-26 February 2023. Vol. 138.Vol. 2. Elsevier. , pp.42-42. (10.1016/j.ymgme.2022.107098)
- Honeybun, L. , Waller-Evans, H. and Lloyd-Evans, E. 2023. Unbiased phenotypic drug screen for CLN3 disease. Presented at: 19th Annual WORLDSymposium™ 2023 Orlando, Florida 21-26 February 2023. Vol. 138.Vol. 2. Elsevier. , pp.167-167. (10.1016/j.ymgme.2022.107150)
- Lloyd-Evans, E. et al. 2023. Glycosphingolipid reduction with miglustat as a therapeutic strategy for CLN3 and other neuronal ceroid lipofuscinoses.. Presented at: 19th Annual WORLDSymposium™ 2023 Orlando, Florida 21-26 February 2023. Vol. 138.Vol. 2. Elsevier. , pp.84. (10.1016/j.ymgme.2022.107212)
- Waller-Evans, H. et al. 2023. Filipin composition and imaging modality dramatically affect cellular cholesterol visualisation with implications for assessing cholesterol levels and localisation across the lysosomal disorders. Presented at: 19th Annual WORLDSymposium™ 2023 Orlando, Florida 21-26 February 2023. Vol. 138.Vol. 2. Elsevier. , pp.133. (10.1016/j.ymgme.2022.107352)
- Waller-Evans, H. et al. 2023. Measuring ion flux via lysosomal channels: Primary and secondary assays for drug discovery across the lysosomal disorders. Presented at: 19th Annual WORLDSymposium™ 2023 Orlando, Florida 21-26 February 2023. Vol. 138.Vol. 2. Elsevier. , pp.133-134. (10.1016/j.ymgme.2022.107353)
2022
- Best, H. L. et al. 2022. The crystal structure of Bacillus thuringiensis Tpp80Aa1 and its interaction with galactose-containing glycolipids. Toxins 14 (12) 863. (10.3390/toxins14120863)
2020
- Cook, S. R. et al. 2020. Visualisation of cholesterol and ganglioside GM1 in zebrafish models of Niemann-Pick type C disease and Smith-Lemli-Opitz syndrome using light sheet microscopy. Histochemistry and Cell Biology 154 , pp.565-578. (10.1007/s00418-020-01925-2)
- Badell Grau, R. A. et al. 2020. Investigating the prevalence of reactive online searching in the COVID-19 pandemic. Journal of Medical Internet Research 22 (10) e19791. (10.2196/19791)
- Fenn, G. et al. 2020. Crystallization and structure of ebselen bound to cysteine 141 of human inositol monophosphatase (IMPase). Acta Crystallographica Section F: Structural Biology Communications F76 (10), pp.469-476. (10.1107/S2053230X20011310)
- Lloyd-Evans, E. and Waller-Evans, H. 2020. Biosynthesis and signalling functions of central and peripheral nervous system neurosteroids in health and disease. Essays in Biochemistry 64 (3), pp.591-606. (10.1042/EBC20200043)
- Cook, S. R. et al. 2020. Detrimental effect of zwitterionic buffers on lysosomal homeostasis in cell lines and iPSC-derived neurons. AMRC Open Research 2 21. (10.12688/amrcopenres.12903.1)
2018
- Morimoto, M. et al., 2018. Bi-allelic CCDC47 variants cause a disorder characterized by woolly hair, liver dysfunction, dysmorphic features, and global developmental delay. American Journal of Human Genetics 103 (5), pp.794-807. (10.1016/j.ajhg.2018.09.014)
2015
- Waller-Evans, H. and Lloyd-Evans, E. 2015. Regulation of TRPML1 function. Biochemical Society Transactions 43 (3), pp.442-446. (10.1042/BST20140311)
2014
- Kaisaki, P. J. et al., 2014. Genetic control of differential acetylation in diabetic rats. PLoS ONE 9 (4) e94555. (10.1371/journal.pone.0094555)
2013
- Waller-Evans, H. et al. 2013. Nutrigenomics of high fat diet induced obesity in mice suggests relationships between susceptibility to fatty liver disease and the proteasome. PLoS ONE 8 (12) e82825. (10.1371/journal.pone.0082825)
2012
- Prömel, S. et al., 2012. Characterization and functional study of a cluster of four highly conserved orphan adhesion-GPCR in mouse. Developmental Dynamics 241 (10), pp.1591-1602. (10.1002/dvdy.23841)
2010
- Waller-Evans, H. et al. 2010. The orphan adhesion-GPCR GPR126 is required for embryonic development in the mouse. PLoS ONE 5 (11) e14047. (10.1371/journal.pone.0014047)
- Lloyd-Evans, E. et al. 2010. Endolysosomal calcium regulation and disease.. Biochemical Society Transactions 38 (6), pp.1458-1464. (10.1042/BST0381458)
2009
- Langenhan, T. et al., 2009. Latrophilin signaling links anterior-posterior tissue polarity and oriented cell divisions in the C. elegans embryo. Developmental Cell 17 (4), pp.494-504. (10.1016/j.devcel.2009.08.008)
Adrannau llyfrau
- Kirkham, E. et al., 2025. Lysosomal pH measurements via dual-imaging microscopy. In: Hughes, S. M. and Basak, I. eds. Lysosomes: Methods and Protocols. Vol. 2976, Methods in Molecular Biology New York, New York, USA: , pp.11-24. (10.1007/978-1-0716-4844-5_2)
Cynadleddau
- Best, H. et al. 2023. The Batten disease associated protein CLN3 is required for the efflux of lysosomal K. Presented at: 19th Annual WORLDSymposium™ 2023 Orlando, Florida 21-26 February 2023. Vol. 138.Vol. 2. Elsevier. , pp.47-47. (10.1016/j.ymgme.2022.107030)
- Best, H. L. et al. 2023. Disease phenotypes present in CLN7 patient fibroblasts are improved following treatment to reduce glycosphingolipid synthesis.. Presented at: 19th Annual WORLDSymposium™ 2023 Orlando, Florida 21-26 February 2023. Vol. 138.Vol. 2. Elsevier. , pp.17. (10.1016/j.ymgme.2022.107029)
- Cook, S. R. et al. 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)
- Fenn, G. D. , Lloyd-Evans, E. and Waller-Evans, H. 2023. Investigation of cannabidiol as a potential therapeutic in Niemann-Pick disease. Presented at: 19th Annual WORLDSymposium™ 2023 Orlando, Florida 21-26 February 2023. Vol. 138.Vol. 2. Elsevier. , pp.42-42. (10.1016/j.ymgme.2022.107098)
- Honeybun, L. , Waller-Evans, H. and Lloyd-Evans, E. 2023. Unbiased phenotypic drug screen for CLN3 disease. Presented at: 19th Annual WORLDSymposium™ 2023 Orlando, Florida 21-26 February 2023. Vol. 138.Vol. 2. Elsevier. , pp.167-167. (10.1016/j.ymgme.2022.107150)
- Lloyd-Evans, E. et al. 2023. Glycosphingolipid reduction with miglustat as a therapeutic strategy for CLN3 and other neuronal ceroid lipofuscinoses.. Presented at: 19th Annual WORLDSymposium™ 2023 Orlando, Florida 21-26 February 2023. Vol. 138.Vol. 2. Elsevier. , pp.84. (10.1016/j.ymgme.2022.107212)
- Waller-Evans, H. et al. 2023. Filipin composition and imaging modality dramatically affect cellular cholesterol visualisation with implications for assessing cholesterol levels and localisation across the lysosomal disorders. Presented at: 19th Annual WORLDSymposium™ 2023 Orlando, Florida 21-26 February 2023. Vol. 138.Vol. 2. Elsevier. , pp.133. (10.1016/j.ymgme.2022.107352)
- Waller-Evans, H. et al. 2023. Measuring ion flux via lysosomal channels: Primary and secondary assays for drug discovery across the lysosomal disorders. Presented at: 19th Annual WORLDSymposium™ 2023 Orlando, Florida 21-26 February 2023. Vol. 138.Vol. 2. Elsevier. , pp.133-134. (10.1016/j.ymgme.2022.107353)
Erthyglau
- Best, H. et al. 2026. The long and short of it: Distinct natural crystal packing strategies of Cry toxins from Bacillus thuringiensis. Structure 34 (5), pp.704-717.e3. (10.1016/j.str.2026.01.014)
- Riseley, R. et al., 2025. Unusual reactivity of 2-amino-1H-indole-3-carboxylate esters. ARKIVOC 2025 (5) 202512417. (10.24820/ark.5550190.p012.417)
- Reeks, J. et al., 2025. High throughput cryo-EM provides structural understanding for modulators of the lysosomal ion channel TRPML1. Structure 33 (8), pp.1374-1385. (10.1016/j.str.2025.05.014)
- Best, H. L. et al. 2025. Niemann-Pick C-like endo-lysosomal dysfunction in DHDDS patient cells, a congenital disorder of glycosylation, can be treated with miglustat. International Journal of Molecular Sciences 26 (4) 1471. (10.3390/ijms26041471)
- Cubitt, J. et al. 2024. Beware of N-Benzoyloxybenzamides. Molecules 29 (21) 5143. (10.3390/molecules29215143)
- Best, H. L. et al. 2023. The role of glycoconjugates as receptors for insecticidal proteins. FEMS Microbiology Reviews 47 (4)(10.1093/femsre/fuad026)
- Somogyi, A. et al., 2023. The synthetic TRPML1 agonist ML-SA1 rescues Alzheimer-related alterations of the endosomal-autophagic-lysosomal system. Journal of Cell Science 136 (6) jcs259875. (10.1242/jcs.259875)
- Fenn, G. D. et al. 2023. Development of a novel anthraquinone-derived fluorescent lysosomal probe. Molecular Genetics and Metabolism 138 (2) 107097. (10.1016/j.ymgme.2022.107097)
- Davies, M. et al. 2023. Acid ceramidase inhibition as a mechanism to treat lysosomal disorders. Molecular Genetics and Metabolism 138 (2) 107069. (10.1016/j.ymgme.2022.107069)
- Best, H. L. et al. 2022. The crystal structure of Bacillus thuringiensis Tpp80Aa1 and its interaction with galactose-containing glycolipids. Toxins 14 (12) 863. (10.3390/toxins14120863)
- Cook, S. R. et al. 2020. Visualisation of cholesterol and ganglioside GM1 in zebrafish models of Niemann-Pick type C disease and Smith-Lemli-Opitz syndrome using light sheet microscopy. Histochemistry and Cell Biology 154 , pp.565-578. (10.1007/s00418-020-01925-2)
- Badell Grau, R. A. et al. 2020. Investigating the prevalence of reactive online searching in the COVID-19 pandemic. Journal of Medical Internet Research 22 (10) e19791. (10.2196/19791)
- Fenn, G. et al. 2020. Crystallization and structure of ebselen bound to cysteine 141 of human inositol monophosphatase (IMPase). Acta Crystallographica Section F: Structural Biology Communications F76 (10), pp.469-476. (10.1107/S2053230X20011310)
- Lloyd-Evans, E. and Waller-Evans, H. 2020. Biosynthesis and signalling functions of central and peripheral nervous system neurosteroids in health and disease. Essays in Biochemistry 64 (3), pp.591-606. (10.1042/EBC20200043)
- Cook, S. R. et al. 2020. Detrimental effect of zwitterionic buffers on lysosomal homeostasis in cell lines and iPSC-derived neurons. AMRC Open Research 2 21. (10.12688/amrcopenres.12903.1)
- Morimoto, M. et al., 2018. Bi-allelic CCDC47 variants cause a disorder characterized by woolly hair, liver dysfunction, dysmorphic features, and global developmental delay. American Journal of Human Genetics 103 (5), pp.794-807. (10.1016/j.ajhg.2018.09.014)
- Waller-Evans, H. and Lloyd-Evans, E. 2015. Regulation of TRPML1 function. Biochemical Society Transactions 43 (3), pp.442-446. (10.1042/BST20140311)
- Kaisaki, P. J. et al., 2014. Genetic control of differential acetylation in diabetic rats. PLoS ONE 9 (4) e94555. (10.1371/journal.pone.0094555)
- Waller-Evans, H. et al. 2013. Nutrigenomics of high fat diet induced obesity in mice suggests relationships between susceptibility to fatty liver disease and the proteasome. PLoS ONE 8 (12) e82825. (10.1371/journal.pone.0082825)
- Prömel, S. et al., 2012. Characterization and functional study of a cluster of four highly conserved orphan adhesion-GPCR in mouse. Developmental Dynamics 241 (10), pp.1591-1602. (10.1002/dvdy.23841)
- Waller-Evans, H. et al. 2010. The orphan adhesion-GPCR GPR126 is required for embryonic development in the mouse. PLoS ONE 5 (11) e14047. (10.1371/journal.pone.0014047)
- Lloyd-Evans, E. et al. 2010. Endolysosomal calcium regulation and disease.. Biochemical Society Transactions 38 (6), pp.1458-1464. (10.1042/BST0381458)
- Langenhan, T. et al., 2009. Latrophilin signaling links anterior-posterior tissue polarity and oriented cell divisions in the C. elegans embryo. Developmental Cell 17 (4), pp.494-504. (10.1016/j.devcel.2009.08.008)
Ymchwil
Diddordebau Ymchwil
Mae fy ymchwil yn canolbwyntio ar egluro swyddogaethau proteinau lysosomal a'u rolau mewn anhwylderau niwrolegol, a datblygu cyffuriau newydd sy'n targedu'r proteinau hyn i'w defnyddio yn y ddau glefydau o heneiddio ac anhwylderau storio lysosomal - clefydau genetig prin a achosir gan ddiffygion mewn proteinau lysosomal.
Fy mhrif ddiddordeb ymchwil yw'r protein NPC1, protein lysosomal sydd â rôl awgrymedig mewn trafnidiaeth colesterol. Mae colli swyddogaeth NPC1 yn asio clefyd math C Niemann-Select, anhwylder storio lysosomol, lle mae plentyn yr effeithir arno yn cael anhawster cerdded a llyncu, anawsterau dysgu, epilepsi a dementia. Gall y triniaethau presennol arafu dilyniant clefydau ond nid ydynt yn mynd i'r afael â'r diffyg gweithgarwch sylfaenol o NPC1. Rwy'n datblygu profion swyddogaethol ar gyfer protein lysosomal NPC1, a fydd yn caniatáu imi gynnal sgriniau cyffuriau ar gyfer moleciwlau a all actifadu NPC1 mewn cleifion math Niemann-Select.
Mae NPC1 hefyd yn cael ei ddefnyddio fel derbynnydd mewngellol gan nifer o firysau, gan gynnwys Ebola, hepatitis C, a coronafeirysau feline. Rwy'n ymchwilio i weld a all cyffuriau sy'n atal protein NPC1 atal SARS-CoV-2 rhag mynd i mewn i gelloedd, a allai alluogi eu hail-bwrpasu cyflym i drin Covid-19.
Aelodau presennol y Lab
Gareth Fenn - myfyriwr PhD
Sian Gardiner - uwch dechnegydd
Marcus Hanley - myfyriwr PhD
Bethany Tattersdill - cynorthwy-ydd ymchwil
Gabby Ward - technegydd
Cydweithredwyr
Dr Emyr Lloyd-Evans (Ysgol y Biowyddorau, Prifysgol Caerdydd)
Dr Ceri Fielding (Ysgol Meddygaeth, Prifysgol Caerdydd)
Yr Athro Simon Pope (Ysgol Cemeg, Prifysgol Caerdydd)
Yr Athro Colin Berry (Ysgol y Biowyddorau, Prifysgol Caerdydd)
Cyllid
Ariennir ymchwil yn fy labordy gan yr Academi Gwyddorau Meddygol, Sefydliad Ymchwil Niemann-Select, Llywodraeth Cymru, a Sefydliad Ymchwil Harrington.
Bywgraffiad
Hanes Gyrfa
2019 - presennol: Darlithydd niwrowyddoniaeth, Sefydliad Darganfod Meddyginiaethau, Prifysgol Caerdydd, lle byddaf yn datblygu cyffuriau newydd sy'n targedu proteinau lysosomal
2012 - 2019: Cydymaith Ymchwil gyda Dr Emyr Lloyd-Evans, Ysgol y Biowyddorau, Prifysgol Caerdydd. Yma, ymchwiliais i'r mecanweithiau sy'n arwain at bathogenesis mewn sawl anhwylder storio lysosomal, a dyma lle datblygais fy niddordeb mewn lysosomau.
2010 - 2012: Cydymaith Ymchwil gyda'r Athro Alun Davies FRS, Ysgol y Biowyddorau, Prifysgol Caerdydd. Yma, ymchwiliais i rôl ffactorau twf mewn datblygiad niwronau, a sut mae hyn yn cael ei effeithio mewn anhwylderau niwrolegol gan gynnwys clefyd Parkinson.
2008 - 2010: Cydymaith Ymchwil gyda'r Athro Dominique Gauguier, Prifysgol Rhydychen. Yma, ymchwiliais i gyfraniad gwahanol enynnau i ddifrifoldeb diabetes math 2.
2005 - 2008: PhD gyda Dr Andreas Russ, Prifysgol Rhydychen, yn ymchwilio i rôl GPR126, GPCR amddifad, yn natblygiad y llygoden.
2004 - 2005: Technegydd gyda Dr Andreas Russ, Prifysgol Rhydychen.
2003 - 2004: Diploma Ôl-raddedig mewn Seicoleg (rhagoriaeth), Prifysgol Oxford Brookes.
2002 - 2003: Histolegydd gyda'r Athro Nick Rawlins, Prifysgol Rhydychen.
1998 - 2002: BSc Anrh (dosbarth 1af) Bioleg Gymhwysol, Prifysgol Caerfaddon.
