Trosolwyg
Fi yw dirprwy gyfarwyddwr yr Is-adran Heintiau ac Imiwnedd ym Mhrifysgol Caerdydd, Ysgol Meddygaeth. Fi hefyd yw Pennaeth y Grŵp Ymchwil Diabetes sy'n arwain y thema Imiwnoleg yn yr Is-adran.
Rwyf wedi cael blynyddoedd lawer o brofiad ymchwil wrth weithio ar sut mae'r system imiwnedd yn niweidio celloedd beta'r pancreas sy'n cynhyrchu inswlin mewn diabetes math 1. Mae fy ymchwil yn canolbwyntio'n bennaf ar achosion a datblygiad diabetes math 1 ac mae wedi cwmpasu imiwnoleg celloedd T, imiwnoleg celloedd B, celloedd T rheoleiddiol, imiwnedd cynhenid – ac yn ystod y blynyddoedd diwethaf, mae ein gwaith wedi cynnwys astudiaethau yn rôl microbiome y perfedd. Fel aelod o Gonsortiwm Diabetes Math 1 y DU, rwyf hefyd wedi bod yn rhan o waith trosiadol wrth ddatblygu imiwnotherapi ar gyfer diabetes math 1 ac mewn treialon clinigol cam 1a cynnar.
Cyhoeddiad
2024
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- Smith, M. J., Boldison, J. and Wong, F. S. 2024. The role of B lymphocytes in type 1 diabetes. Cold Spring Harbor Perspectives in Medicine (10.1101/cshperspect.a041593)
- Yang, X. et al. 2024. Gut microbiota from B-cell-specific TLR9-deficient NOD mice promote IL-10 + Breg cells and protect against T1D. Frontiers in Immunology 15, article number: 1413177. (10.3389/fimmu.2024.1413177)
- Wang, P. et al. 2024. Tlr9 deficiency in B cells leads to obesity by promoting inflammation and gut dysbiosis. Nature Communications 15(1), article number: 4232. (10.1038/s41467-024-48611-8)
- Zhang, L., Wang, P., Huang, J., Xing, Y., Wong, F. S., Suo, J. and Wen, L. 2024. Gut microbiota and therapy for obesity and type 2 diabetes. Frontiers in Endocrinology 15, article number: 1333778. (10.3389/fendo.2024.1333778)
- Pearson, J. A., Hu, Y., Peng, J., Wong, F. S. and Wen, L. 2024. TLR5-deficiency controls dendritic cell subset development in an autoimmune diabetes-susceptible model. Frontiers in Immunology 15, article number: 1333967. (10.3389/fimmu.2024.1333967)
2023
- Hanna, S. J. et al. 2023. Single-cell RNAseq identifies clonally expanded antigen-specific T-cells following intradermal injection of gold nanoparticles loaded with diabetes autoantigen in humans. Frontiers in Immunology 14, article number: 1276255. (10.3389/fimmu.2023.1276255)
- Pearson, J. A. et al. 2023. NLRP6 deficiency expands a novel CD103 + B cell population that confers immune tolerance in NOD mice. Frontiers in Immunology 14, article number: 1147925. (10.3389/fimmu.2023.1147925)
- Okada, M. et al. 2023. Islet‐specific CD8+ T cells gain effector function in the gut lymphoid tissues via bystander activation not molecular mimicry. Immunology & Cell Biology 101(1), pp. 36-48. (10.1111/imcb.12593)
2022
- Pearson, J. A. et al. 2022. IgM-associated gut bacteria in obesity and type 2 diabetes in C57BL/6 mice and humans. Diabetologia 65(8), pp. 1398-1411. (10.1007/s00125-022-05711-8)
- Chan, K., Wong, F. S. and Pearson, J. A. 2022. Circadian rhythms and pancreas physiology: A review. Frontiers in Endocrinology 13, article number: 920261. (10.3389/fendo.2022.920261)
- Majewska-Szczepanik, M. et al. 2022. Obesity aggravates contact hypersensitivity reaction in mice. Contact Dermatitis 87(1), pp. 28-39. (10.1111/cod.14088)
- Jia, J., Kang, Q., Liu, S., Song, Y., Wong, F. S., Qiu, Y. and Li, M. 2022. Artemether and aspterric acid induce pancreatic alpha cells to transdifferentiate into beta cells in zebrafish. British Journal of Pharmacology 179(9), pp. 1962-1977. (10.1111/bph.15769)
- Green, E. A., Cooke, A. C., Piganelli, J. D., Richardson, S. J., Wen, L. and Wong, F. S. 2022. Editorial: Immunopathology of Type 1 Diabetes. Frontiers in Immunology 13, article number: 852963. (10.3389/fimmu.2022.852963)
- Boldison, J. et al. 2022. Activated but functionally impaired memory Tregs are expanded in slow progressors to type 1 diabetes. Diabetologia 65, article number: 343–355. (10.1007/s00125-021-05595-0)
- Huang, J., Pearson, J. A., Wong, F. S., Wen, L. and Zhou, Z. 2022. Innate immunity in latent autoimmune diabetes in adults (LADA). Diabetes/Metabolism Research and Reviews 38(1), article number: e3480. (10.1002/dmrr.3480)
- Roy Chowdhury, S., Thomas, R. L., Dunseath, G. J., Luzio, S. D., Wong, F. S. and Owens, D. R. 2022. Incidence of diabetic retinopathy in newly diagnosed subjects with type 2 diabetes mellitus over 5 years: Contribution of B-cell function. Journal of Diabetes and its Complications 36(1), article number: 108028. (10.1016/j.jdiacomp.2021.108028)
- Tatovic, D. et al. 2022. Safety of the use of gold nanoparticles conjugated with proinsulin peptide and administered by hollow microneedles as an immunotherapy in Type 1 diabetes. Immunotherapy Advances 2(1), article number: ltac002. (10.1093/immadv/ltac002)
- Buzzetti, R., Maddaloni, E., Gaglia, J. G., Leslie, R. D., Wong, F. S. and Boehm, B. O. 2022. Adult-onset autoimmune diabetes. Nature Reviews Disease Primers 8, article number: 63. (10.1038/s41572-022-00390-6)
2021
- Quinn, L. M., Wong, F. S. and Narendran, P. 2021. Environmental determinants of type 1 diabetes: from association to proving causality. Frontiers in Immunology 12, article number: 737964. (10.3389/fimmu.2021.737964)
- Boldison, J. and Wong, F. S. 2021. Regulatory B cells: role in type 1 diabetes. Frontiers in Immunology 12, article number: 746187. (10.3389/fimmu.2021.746187)
- Pearson, J. A., Voisey, A. C., Boest Bjerg, K., Wong, F. S. and Wen, L. 2021. Circadian rhythm modulation of microbes during health and infection. Frontiers in Microbiology 12, article number: 721004. (10.3389/fmicb.2021.721004)
- Huang, J. et al. 2021. IL-10 deficiency accelerates type 1 diabetes development via modulation of innate and adaptive immune cells and gut microbiota in BDC2.5 NOD mice. Frontiers in Immunology 12, article number: 702955. (10.3389/fimmu.2021.702955)
- Pearson, J. A., Wong, F. S. and Wen, L. 2021. Inflammasomes and type 1 diabetes. Frontiers in Immunology 12, article number: 686956. (10.3389/fimmu.2021.686956)
- Siah, Q. Z., Ubeysekara, N. H., Taylor, P. N., Davies, S. J., Wong, F., Dayan, C. M. and Alhadj Ali, M. 2021. Referral rates of patients with diabetes to secondary care are inversely related to the prevalence of diabetes in each primary care practice and confidence in treatment, not to HbA1c level. Primary Care Diabetes 15(3), pp. 513-517. (10.1016/j.pcd.2021.02.004)
- Battaglia, M., Buckner, J. H., Levings, M. K., Richardson, S. J., Wong, F. S. and Tree, T. I. 2021. Identifying the ‘Achilles heel’ of type 1 diabetes. Clinical and Experimental Immunology 204(2), pp. 167-178. (10.1111/cei.13570)
- Wong, F. S. and Tree, T. I. 2021. Historical and new insights into pathogenesis of type 1 diabetes (2). Clinical and Experimental Immunology 204(2), pp. 165-166. (10.1111/cei.13597)
- Boldison, J., Thayer, T. C., Davies, J. and Wong, F. S. 2021. Natural protection from Type 1 Diabetes in Non obese diabetic (Nod) mice is characterised by a unique pancreatic islet phenotype. Diabetes 70(3), article number: db200945. (10.2337/db20-0945)
- Thayer, T. C., Davies, J., Pearson, J. A., Hanna, S. J., Wen, L. and Wong, F. S. 2021. Differentiating MHC-dependent and -independent mechanisms of lymph node stromal cell regulation of Proinsulin-specific CD8+ T-Cells in type 1 diabetes. Diabetes 70(2), pp. 529-537., article number: db191050. (10.2337/db19-1050)
- Singh, R. K. et al. 2021. Using gold nanoparticles for enhanced intradermal delivery of poorly soluble auto-antigenic peptides. Nanomedicine: Nanotechnology, Biology and Medicine 32, article number: 102321. (10.1016/j.nano.2020.102321)
- Huang, J. et al. 2021. Toll-like receptor 7 deficiency suppresses type 1 diabetes development by modulating B-cell differentiation and function. Cellular and Molecular Immunology 18, pp. 328-338. (10.1038/s41423-020-00590-8)
- Sha, S. et al. 2021. TLR9-deficiency in B cells promotes immune tolerance via IL-10 in a type 1 diabetes mouse model. Diabetes 70(2), pp. 504-515. (10.2337/db20-0373)
- Boldison, J., Da Rosa, L. C. and Wong, F. S. 2021. Regulatory B cells in type 1 diabetes. In: Mion, F. and Tonon, S. eds. Regulatory B Cells., Vol. 2270. Methods in Molecular Biology New York, US: Humana Press, pp. 419-435., (10.1007/978-1-0716-1237-8_22)
2020
- Pearson, J. A., Wong, F. S. and Wen, L. 2020. Crosstalk between circadian rhythms and the microbiota. Immunology 161(4), pp. 278-290. (10.1111/imm.13278)
- Pearson, J. A. et al. 2020. Insulin-reactive T cells convert diabetogenic insulin-reactive VH125 B cells into tolerogenic cells by reducing germinal center T:B cell Interactions in NOD mice. Frontiers in Immunology 11, article number: 585886. (10.3389/fimmu.2020.585886)
- Huang, J. et al. 2020. Altered systemic and intestinal IgA immune responses in individuals with type 1 diabetes. Journal of Clinical Endocrinology and Metabolism 105(12), article number: dgaa590. (10.1210/clinem/dgaa590)
- Boldison, J., Camargo Da Rosa, L., Davies, J., Wen, L. and Wong, F. S. 2020. Dendritic cells license regulatory B cells to produce IL-10 and mediate suppression of antigen-specific CD8 T cells. Cellular and Molecular Immunology 17, pp. 843 - 855. (10.1038/s41423-019-0324-z)
- Hanna, S. J. et al. 2020. Slow progressors to type 1 diabetes lose islet autoantibodies over time, have few islet antigen-specific CD8+ T cells and exhibit a distinct CD95hi B cell phenotype. Diabetologia 63, pp. 1174-1185., article number: Diabetologia volume 63, pages1174–1185(2020). (10.1007/s00125-020-05114-7)
- Arikat, F. et al. 2020. Targeting proinsulin to local immune cells using an intradermal microneedle delivery system; a potential antigen-specific immunotherapy for type 1 diabetes. Journal of Controlled Release 322, pp. 593-601. (10.1016/j.jconrel.2020.02.031)
- Huang, J. et al. 2020. Gut microbial metabolites alter IgA immunity in type 1 diabetes. JCI Insight 5(10), article number: e135718. (10.1172/jci.insight.135718)
- Wong, F. S. and Wen, L. 2020. A predictive CD8+ T cell phenotype for T1DM progression. Nature Reviews Endocrinology 16, pp. 198-199. (10.1038/s41574-020-0330-3)
- Thayer, T. C., Kakabadse, D., Boldison, J. and Wong, F. S. 2020. Assessing immune responses in the nonobese diabetic mouse model of type 1 Diabetes. In: Animal Models of Diabetes., Vol. 2128. Methods in Molecular Biology New York, NY, USA: Humana Press, pp. 269-289., (10.1007/978-1-0716-0385-7_18)
- Chen, D., Thayer, T. C., Wen, L. and Wong, F. S. 2020. Mouse models of autoimmune diabetes: the nonobese diabetic (NOD) mouse. In: Animal Models of Diabetes., Vol. 2128. Methods in Molecular Biology New York, NY, USA: Humana Press, pp. 87-92., (10.1007/978-1-0716-0385-7_6)
2019
- Wong, F. S. and Tree, T. I. 2019. Historical and new insights into pathogenesis of type 1 diabetes. Clinical and Experimental Immunology 198(3), pp. 292-293. (10.1111/cei.13396)
- Boldison, J., Da Rosa, L. C., Buckingham, L., Davies, J., Wen, L. and Wong, F. S. 2019. Phenotypically distinct anti-insulin B cells repopulate pancreatic islets after anti-CD20 treatment in NOD mice. Diabetologia 62(11), pp. 2052-2065. (10.1007/s00125-019-04974-y)
- Pearson, J. A. et al. 2019. Norovirus changes susceptibility to type 1 diabetes by altering intestinal microbiota and immune cell functions. Frontiers in Immunology 10, article number: 2654. (10.3389/fimmu.2019.02654)
- Choudhury, M. et al. 2019. Association between HbA1c and the development of cystic fibrosis‐related diabetes. Diabetic Medicine 36(10), pp. 1251-1255. (10.1111/dme.13912)
- Powell, W. et al. 2019. Detecting autoreactive B cells in the peripheral blood of people with type 1 diabetes using ELISpot. Journal of Immunological Methods 471, pp. 61-65. (10.1016/j.jim.2019.05.007)
- Pearson, J. A. et al. 2019. Altered gut microbiota activate and expand insulin B15-23-Reactive CD8+ T-Cells. Diabetes 68(5), pp. 1002-1013. (10.2337/db18-0487)
- Dul, M. et al. 2019. Conjugation of a peptide autoantigen to gold nanoparticles for intradermally administered antigen specific immunotherapy. International Journal of Pharmaceutics 562, pp. 303-312. (10.1016/j.ijpharm.2019.03.041)
2018
- Liu, M. et al. 2018. Toll-like receptor 9 negatively regulates pancreatic islet beta cell growth and function in a mouse model of type 1 diabetes. Diabetologia 61(11), pp. 2333-2343. (10.1007/s00125-018-4705-0)
- Hu, Y., Peng, J., Li, F., Wong, F. and Wen, L. 2018. Evaluation of different mucosal microbiota leads to gut microbiota-based prediction of type 1 diabetes in NOD mice. Scientific Reports 8 (10.1038/s41598-018-33571-z)
- Szczepanik, M., Majewska-Szczepanik, M., Wong, F. S., Kowalczyk, P., Pasare, C. and Wen, L. 2018. Regulation of contact sensitivity in non-obese diabetic (NOD) mice by innate immunity. Contact Dermatitis 79(4), pp. 197. (10.1111/cod.13046)
- Pearson, J. A., Agriantonis, A., Wong, F. S. and Wen, L. 2018. Modulation of the immune system by the gut microbiota in the development of type 1 diabetes. Human Vaccines and Immunotherapeutics 14(11), pp. 2580-2596. (10.1080/21645515.2018.1514354)
- Gülden, E. et al. 2018. TRIF deficiency protects non-obese diabetic mice from type 1 diabetes by modulating the gut microbiota and dendritic cells. Journal of Autoimmunity 93, pp. 57-65. (10.1016/j.jaut.2018.06.003)
- Powell, W. E. et al. 2018. Loss of CXCR3 expression on memory B cells in individuals with long-standing type 1 diabetes. Diabetologia 61, pp. 1794-1803. (10.1007/s00125-018-4651-x)
- Long, A. E. et al. 2018. Characteristics of slow progression to diabetes in multiple islet autoantibody-positive individuals from five longitudinal cohorts: the SNAIL study. Diabetologia 61(6), pp. 1484-1490. (10.1007/s00125-018-4591-5)
- Da Rosa, L. C., Boldison, J., De Leenheer, E., Davies, J., Wen, L. and Wong, F. S. 2018. B cell depletion reduces T cell activation in pancreatic islets in a murine autoimmune diabetes model. Diabetologia 61(6), pp. 1397-1410. (10.1007/s00125-018-4597-z)
- James, E. A. et al. 2018. Combinatorial detection of autoreactive CD8+ T cells with HLA-A2 multimers: a multi-centre study by the Immunology of Diabetes Society T Cell Workshop. Diabetologia 61(3), pp. 658-670. (10.1007/s00125-017-4508-8)
- Tan, Q. et al. 2018. Activation-induced cytidine deaminase deficiency accelerates autoimmune diabetes in NOD mice. JCI Insight 3(1), article number: 95882. (10.1172/jci.insight.95882)
2017
- Dul, M. et al. 2017. Hydrodynamic gene delivery in human skin using a hollow microneedle device. Journal of Controlled Release 265, pp. 120-131. (10.1016/j.jconrel.2017.02.028)
- Zhao, X., Coulman, S. A., Hanna, S. J., Wong, F. S., Dayan, C. M. and Birchall, J. C. 2017. Formulation of hydrophobic peptides for skin delivery via coated microneedles. Journal of Controlled Release 265, pp. 2-13. (10.1016/j.jconrel.2017.03.015)
- Reeves, P. L., Rudraraju, R., Liu, X., Wong, F. S., Hamilton-Williams, E. E. and Steptoe, R. J. 2017. APC-targeted proinsulin expression inactivates insulin-specific memory CD8+ T cells in NOD mice. Immunology and Cell Biology 95(9), pp. 765-774. (10.1038/icb.2017.48)
- Reeves, P., Rudraraju, R., Wong, F., Hamilton-Williams, E. and Steptoe, R. 2017. Antigen presenting cell-targeted proinsulin expression converts insulin-specific CD8(+) T-cell priming to tolerance in autoimmune-prone NOD mice. European Journal of Immunology 47(9), pp. 1550-1561. (10.1002/eji.201747089)
- Recino, A., Barkan, K., Wong, F. S., Ladds, G., Cooke, A. and Wallberg, M. 2017. Hyperglycaemia does not affect antigen-specific activation and cytolytic killing by CD8+ T cells in vivo. Bioscience Reports 37(4), article number: 1079. (10.1042/BSR20171079)
- Alhadj Ali, M. et al. 2017. Metabolic and immune effects of immunotherapy with proinsulin peptide in human new-onset type 1 diabetes. Science Translational Medicine 9(402), article number: eaaf7779. (10.1126/scitranslmed.aaf7779)
- Li, Y. Y. et al. 2017. Nucleotide-binding oligomerization domain-containing protein 2 (Nod2) modulates T1DM susceptibility by gut microbiota. Journal of Autoimmunity 82, pp. 85-95. (10.1016/j.jaut.2017.05.007)
- Wen, L. and Wong, F. 2017. Dietary short chain fatty acids protect against type 1 diabetes. Nature Immunology 18(5), pp. 484-486. (10.1038/ni.3730)
- Wallberg, M. et al. 2017. Anti-CD3 treatment up-regulates programmed cell death protein-1 expression on activated effector T cells and severely impairs their inflammatory capacity. Immunology 151(2), pp. 248-260. (10.1111/imm.12729)
- Fishman, S. et al. 2017. Adoptive transfer of mRNA-Transfected T cells redirected against diabetogenic CD8 T cells can prevent diabetes. Molecular Therapy 25(2), pp. 456-464. (10.1016/j.ymthe.2016.12.007)
- Hu, Y., Wong, F. S. and Wen, L. 2017. Antibiotics, gut microbiota, environment in early life and type 1 diabetes. Pharmacological Research 119, pp. 219-226. (10.1016/j.phrs.2017.01.034)
2016
- Boldison, J. and Wong, F. S. 2016. Immune and pancreatic β cell interactions in type 1 diabetes. Trends in Endocrinology & Metabolism 27(12), pp. 856-867. (10.1016/j.tem.2016.08.007)
- Williams, G. M. et al. 2016. Beta cell function and ongoing autoimmunity in long-standing, childhood onset type 1 diabetes. Diabetologia 59(12), pp. 2722-2726. (10.1007/s00125-016-4087-0)
- Thayer, T. C. et al. 2016. Peripheral proinsulin expression controls low-avidity proinsulin-reactive CD8 T Cells in type 1 diabetes. Diabetes 65(11), pp. 3429-3439. (10.2337/db15-1649)
- Clement, M. et al. 2016. Targeted suppression of autoreactive CD8+ T-cell activation using blocking anti-CD8 antibodies. Scientific Reports 6, article number: 35332. (10.1038/srep35332)
- Tai, N. et al. 2016. Microbial antigen mimics activate diabetogenic CD8 T cells in NOD mice. Journal of Experimental Medicine 213(10), pp. 2129. (10.1084/jem.20160526)
- Hu, Y., Jin, P., Peng, J., Zhang, X., Wong, F. S. and Wen, L. 2016. Different immunological responses to early-life antibiotic exposure affecting autoimmune diabetes development in NOD mice. Journal of Autoimmunity 72, pp. 47-56. (10.1016/j.jaut.2016.05.001)
- Tai, N., Wong, F. S. and Wen, L. 2016. The role of the innate immune system in destruction of pancreatic beta cells in NOD mice and humans with type I diabetes. Journal of Autoimmunity 71, pp. 26-34. (10.1016/j.jaut.2016.03.006)
- Thayer, T. C. and Wong, F. S. 2016. Tracking immunological responses of Islet antigen-specific T cells in the Nonobese Diabetic (NOD) Mouse Model of Type 1 Diabetes. In: Gillespie, K. ed. Type-1 Diabetes: Methods and Protocols., Vol. 1433. Methods in Molecular Biology Humana Press, New York, NY, pp. 127-134., (10.1007/7651_2015_293)
- De Leenheer, E. and Wong, F. S. 2016. Adoptive transfer of autoimmune diabetes using immunodeficient Non Obese Diabetic (NOD) mice. In: Gillespie, K. M. ed. Type-1 Diabetes: Methods and Protocols., Vol. 1433. Methods in Molecular Biology Humana Press, New York, NY, pp. 135-140., (10.1007/7651_2015_294)
- Pearson, J. A. et al. 2016. Proinsulin expression shapes the TCR repertoire but fails to control the development of low-avidity insulin-reactive CD8+ T cells. Diabetes 65(6), pp. 1679-1689. (10.2337/db15-1498)
- Peng, J., Hu, Y., Wong, F. S. and Wen, L. 2016. The gut microbiome in the NOD mouse. In: Gillespie, K. M. ed. Type-1 Diabetes: Methods and Protocols., Vol. 1433. Methods in Molecular Biology Vol. 1433. Springer, pp. 169-177., (10.1007/7651_2016_331)
- Zhao, X. et al. 2016. Microneedle delivery of autoantigen for immunotherapy in type 1 diabetes. Journal of Controlled Release 223, pp. 178-187. (10.1016/j.jconrel.2015.12.040)
- Pearson, J. A., Wong, F. S. and Wen, L. 2016. The importance of the Non Obese Diabetic (NOD) mouse model in autoimmune diabetes. Journal of Autoimmunity 66, pp. 76-88. (10.1016/j.jaut.2015.08.019)
- Barbera Betancourt, A., Emery, J. L., Recino, A., Wong, F. S., Cooke, A., Okkenhaug, K. and Wallberg, M. 2016. Inhibition of phosphoinositide 3-Kinase p110delta does not affect T cell driven development of Type 1 diabetes despite significant effects on cytokine production. PLoS ONE 11(1), article number: e0146516. (10.1371/journal.pone.0146516)
2015
- Pearson, J. A. and Wong, F. S. 2015. Identification of islet antigen-specific CD8 T cells using MHCI-peptide tetramer reagents in the non obese diabetic (NOD) mouse model of type 1 diabetes. In: Gillespie, K. M. ed. Type-1 Diabetes., Vol. 1433. Methods in Molecular Biology Springer, pp. 119-125., (10.1007/7651_2015_295)
- Alhadj Ali, M. et al. 2015. Topical steroid therapy induces pro-tolerogenic changes in Langerhans cells in human skin. Immunology 146(3), pp. 411-422. (10.1111/imm.12518)
- Hu, Y., Peng, J., Tai, N., Hu, C., Zhang, X., Wong, F. S. and Wen, L. 2015. Maternal antibiotic treatment protects offspring from diabetes development in nonobese diabetic mice by generation of tolerogenic APCs. Journal of Immunology 195(9), pp. 4176-4184. (10.4049/jimmunol.1500884)
- Culina, S. et al. 2015. Materno-Fetal transfer of preproinsulin through the neonatal FC receptor prevents autoimmune diabetes. Diabetes 64(10), pp. 3532-3542. (10.2337/db15-0024)
- Hu, C. et al. 2015. NLRP3 deficiency protects from type 1 diabetes through the regulation of chemotaxis into the pancreatic islets. Proceedings of the National Academy of Sciences 112(36), pp. 11318-11323. (10.1073/pnas.1513509112)
- Gülden, E., Wong, F. S. and Wen, L. 2015. The gut microbiota and Type 1 Diabetes. Clinical Immunology 159(2), pp. 143-153. (10.1016/j.clim.2015.05.013)
- Motozono, C. et al. 2015. Distortion of the major histocompatibility complex class I binding groove to accommodate an insulin-derived 10-Mer peptide. Journal of Biological Chemistry 290(31), pp. 18924-18933. (10.1074/jbc.M114.622522)
- Tatovic, D., Young, P., Kochba, E., Levin, Y., Wong, F. S. and Dayan, C. M. 2015. Fine-needle aspiration biopsy of the lymph node: a novel tool for the monitoring of immune responses after skin antigen delivery. Journal of Immunology 195(1), pp. 386-392. (10.4049/jimmunol.1500364)
- Sayers, A. et al. 2015. Evidence for a persistent, major excess in all cause admissions to hospital in children with type-1 diabetes: results from a large Welsh national matched community cohort study. BMJ Open 5, article number: e005644. (10.1136/bmjopen-2014-005644)
- Tai, N., Wong, F. S. and Wen, L. 2015. The role of gut microbiota in the development of type 1, type 2 diabetes mellitus and obesity. Reviews in Endocrine and Metabolic Disorders 16(1), pp. 55-65. (10.1007/s11154-015-9309-0)
- Lewis, M. D., de Leenheer, E., Fishman, S., Siew, L. K., Gross, G. and Wong, F. S. 2015. A reproducible method for the expansion of mouse CD8+ T lymphocytes. Journal of Immunological Methods 417, pp. 134-138. (10.1016/j.jim.2015.01.004)
2014
- Kleffel, S. et al. 2014. Interleukin-10+ regulatory B cells arise within antigen-experienced CD40+B cells to maintain tolerance to islet autoantigens. Diabetes 64(1), pp. 158-171. (10.2337/db13-1639)
- Pearson, J., Thayer, T. C., McLaren, J. E., Miners, K. L., Ladell, K. I., Price, D. and Wong, F. S. 2014. Analysis of the repertoire of insulin-reactive CD8(+) T cells [Abstract]. Immunology 143(S2), pp. 152-152. (10.1111/imm.12406)
- Perez, S., Fishman, S., Bordowitz, A., Margalit, A., Wong, F. and Gross, G. 2014. Selective immunotargeting of diabetogenic CD4 T cells by genetically redirected T cells. Immunology 143(4), pp. 609-617. (10.1111/imm.12340)
- Yüksel, M. et al. 2014. Hepatitis mouse models: from acute-to-chronic autoimmune hepatitis. International Journal of Experimental Pathology 95(5), pp. 309-320. (10.1111/iep.12090)
- Peng, J., Narasimhan, S., Marchesi, J. R., Benson, A., Wong, F. S. and Wen, L. 2014. Long term effect of gut microbiota transfer on diabetes development. Journal of Autoimmunity 53, pp. 85-94. (10.1016/j.jaut.2014.03.005)
- Tan, Q., Majewska-Szczepanik, M., Zhang, X., Szczepanik, M., Zhou, Z., Wong, F. S. and Wen, L. 2014. IRAK-M deficiency promotes the development of type 1 diabetes in NOD mice. Diabetes 63(8), pp. 2761-2775. (10.2337/db13-1504)
- Hsu, H. et al. 2014. Endoplasmic reticulum targeting alters regulation of expression and antigen presentation of proinsulin. The Journal of Immunology 192(11), pp. 4957-4966. (10.4049/jimmunol.1300631)
- Wong, F. 2014. How does B-Cell tolerance contribute to the protective effects of diabetes following induced mixed chimerism in autoimmune diabetes?. Diabetes 63(6), pp. 1855-1857. (10.2337/db14-0327)
2013
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Ymchwil
Mae ein gwaith ymchwil mewn diabetes math 1 yn dechrau o wyddoniaeth sylfaenol i geisio deall pam mae unigolion yn datblygu diabetes. Ynghyd ag astudio'r prosesau sy'n arwain at glefyd, rydym hefyd yn gweithio ar nifer o brosiectau i ddatblygu imiwnotherapi i atal diabetes, ac mae gennym hefyd gydweithrediad agos iawn gyda'r Athro Colin Dayan wrth ddatblygu imiwnotherapi ar gyfer pobl sydd â diabetes math 1.
Rydym wedi cael ein hariannu dros nifer o flynyddoedd gan y Cyngor Ymchwil Feddygol, Sefydliad Ymchwil Diabetes Ieuenctid (JDRF), Diabetes UK, y British Council, European Foundation for the Study of Diabetes, Diabetes Research and Wellness Foundation. Mae myfyrwyr PhD yn y grŵp wedi cael eu hariannu gan y MRC, Diabetes UK a Cnpq (Brasil).
Mae ein gwaith yn canolbwyntio ar nifer o wahanol feysydd.
1. Rôl celloedd T cytotoxic CD8 yn natblygiad diabetes.
Rydym wedi astudio celloedd CD8 T adweithiol inswlin, gyda'r nod o ddeall pam mae'r celloedd hyn yn niweidio celloedd beta islet sy'n cynhyrchu inswlin yn ogystal â sut i'w rheoleiddio.
2. Rôl celloedd B yn y pathogenesis a rheoleiddio diabetes.
Mae celloedd B yn cynhyrchu gwrthgyrff, sy'n arwydd da o ddatblygiad diabetes math 1 yn y dyfodol. Nid yw'r gwrthgyrff hyn eu hunain yn achosi difrod, ond mae'r celloedd B sy'n eu cynhyrchu yn ymwneud â chyfathrebu â'r celloedd T i achosi diabetes. Rydym hefyd yn gwybod y gallai rhai celloedd B allu rheoleiddio celloedd T niweidiol. Rydym yn astudio'r celloedd rheoleiddio hyn ac a ellid eu cynyddu i helpu i reoli celloedd T niweidiol mewn diabetes.
Yn ogystal, mae celloedd B i'w cael yn yr ynysoedd pancreatig mewn pobl â diabetes math 1 - nhw yw'r ail fwyaf niferus ar ôl celloedd T CD8. Rydym wedi astudio nodweddion celloedd B yng ngwaed pobl sydd â diabetes math 1 i brofi a oes gwahaniaethau rhwng pobl nad oes ganddynt ddiabetes. Gwelsom fod marciwr mudo yn is ar rai celloedd cof B ac maent bellach yn astudio'r celloedd B hyn ymhellach.
3. Datblygu imiwnotherapi gan ddefnyddio derbynyddion antigen chimerig
Mae derbynyddion antigen Chimerig (CARs) sy'n addasu celloedd T ar gyfer therapi mewn canser bellach wedi'u cymeradwyo ar gyfer therapi dynol gan yr FDA (UDA). Rydym wedi bod yn gweithio ar strategaeth debyg ar gyfer diabetes math 1 gyda'r Athro Gideon Gross o Sefydliad Migal yn Israel i ddylunio dull i leihau'r celloedd CD8 T cytotoxic niweidiol sy'n niweidio'r ynysoedd. Rydym yn addasu celloedd cytotoxic yn ogystal â chelloedd T sy'n gallu rheoli celloedd T eraill i'w gwneud yn targedu'r celloedd sy'n niweidio'r celloedd beta islet yn benodol. Mae hwn yn fath newydd o imiwnotherapi sy'n dal i fod yng nghamau cynnar y datblygiad.
4. Astudiaeth o ficrobiome'r perfedd.
Mae diabetes math 1 yn digwydd oherwydd ffactorau tueddiad genetig yn ogystal â rhyngweithiad o'r ffactorau hyn â'r amgylchedd. Mae diabetes math 1 yn cynyddu ar gyfradd gyflymach nag y gellir ei esbonio gan newidiadau mewn geneteg. Mae ein hastudiaethau gyda'r Athro Li Wen ym Mhrifysgol Iâl wedi bod i ymchwilio i rôl bacteria y perfedd wrth ddylanwadu ar ddiabetes math 1.
5. Astudiaeth o bobl sydd mewn perygl o ddatblygu diabetes nad ydynt wedi symud ymlaen i ddiabetes math 1.
Mae celloedd B yn cynhyrchu gwrthgyrff, sy'n arwydd da o ddatblygiad diabetes math 1 yn y dyfodol. Ynghyd â Dr Kathleen Gillespie ym Mhrifysgol Bryste, rydym wedi bod yn astudio celloedd imiwnedd mewn pobl sydd â risg uchel o ddatblygu diabetes math 1, oherwydd bod ganddynt ddau neu fwy o awtogwrthgyrff sy'n gysylltiedig â datblygu diabetes ond nad ydynt wedi dod yn diabetig o hyd ar ôl 10 mlynedd.
Bywgraffiad
Anrhydeddau a dyfarniadau
2021. Gwobr Gwyddonydd Sylfaenol Kayla a Gerold Grodsky am gyfraniadau mawr i Ymchwil Diabetes Math 1
2019 Cymrawd Cymdeithas Ddysgedig Cymru
Darlith Dorothy Hodgkin 2018 , Diabetes UK
2007, 2010 Gwobr Mary Jane Kugel, Sefydliad Ymchwil Diabetes Ieuenctid
2000-2007 Ymddiriedolaeth Wellcome Uwch Gymrodoriaeth mewn Gwyddoniaeth Glinigol
1996-2000 Gwobr Datblygu Gyrfa, Sefydliad Ymchwil Diabetes Ieuenctid
1994-1996 Cymrodoriaeth Ôl-ddoethurol, Sefydliad Ymchwil Diabetes Ieuenctid I
1993 Cymrodoriaeth Deithio, Cyngor Ymchwil Meddygol (DU)
1989-1992 Cymrodoriaeth Hyfforddiant, Cyngor Ymchwil Meddygol (DU)
Safleoedd academaidd blaenorol
- 2010- presennol: Athro Diabetes a Metabolaeth Arbrofol, Is-adran Heintiau ac Imiwnedd, Imiwnedd Systemau URI, Prifysgol Caerdydd; Meddyg Ymgynghorol Anrhydeddus mewn Diabetes, Bwrdd Iechyd Caerdydd a'r Fro, Caerdydd, UK
- 2008-2010: Athro Imiwnoleg, Adran Meddygaeth Cellog a Moleciwlaidd, Prifysgol Bryste, Bryste UK; Meddyg Ymgynghorol Anrhydeddus mewn Endocrinoleg a Diabetes, Ymddiriedolaeth Gofal Iechyd GIG Bryste, Bryste, UK
- 2007-2008: Darllenydd mewn Imiwnoleg, Adran Meddygaeth Cellog a Moleciwlaidd, Prifysgol Bryste, Bryste UK; Meddyg Ymgynghorol Anrhydeddus mewn Endocrinoleg a Diabetes United Bristol NHS Healthcare Trust, Bryste, UK
- 2000-2007: Ymddiriedolaeth Wellcome Uwch Gymrawd mewn Gwyddoniaeth Glinigol, Adran Meddygaeth Cellog a Moleciwlaidd, Ysgol Gwyddorau Meddygol, Prifysgol Bryste, Bryste UK; Meddyg Ymgynghorol Anrhydeddus mewn Endocrinoleg a Diabetes, Ymddiriedolaeth Gofal Iechyd GIG Bryste, Bryste, UK
Pwyllgorau ac adolygu
Cynghori Gwyddonol
2024 - Grŵp Cynghori Gwyddoniaeth ac Ymchwil Diabetes UK
2023 - Aelod presennol o'r Pwyllgor Ymchwil a Meddygaeth Academaidd, Coleg Brenhinol y Meddygon, Llundain
Pwyllgor Rhaglen 2020-2023 ar gyfer Cynhadledd Broffesiynol Flynyddol Diabetes UK
2020-2022 Cadeirydd Bwrdd Cynghori Gwyddonol JDRF UK
2018-2020 Aelod o Fwrdd Cynghori Gwyddonol JDRF UK
2017-2023 Dirprwy Gadeirydd Grŵp Astudiaethau Clinigol (Pathogenesis) Diabetes UK
Pwyllgor Cynghori Blaenoriaeth Ymchwil JDRF 2009-2011
2000-2004. Aelod o Bwyllgor Llywio'r "Canolfan Datblygu Brechlyn Diabetes" (DVDC), ar y cyd Awstralia NHMRC a JDRF
Golygyddol
2021-2024 Golygydd Cyswllt, Diabetologia
2020-2021 Golygydd Pwnc Ymchwil Frontiers mewn Imiwnoleg
Adroddiadau Gwyddonol Golygydd Cyswllt 2019-2021
1999-2021 Golygydd Cyswllt, Meddygaeth Foleciwlaidd Gyfredol