Professor Roger Barker

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Professor Roger Barker

Parkinson's and Huntington's disease

Email: rab46@cam.ac.uk     |     Departmental Affiliation: Clinical Neurosciences　

Laboratory: John van Geest Centre for Brain Repair, Cambridge Biomedical Campus

www.thebarkerwilliamsgraylab.co.uk/　

Research

Plain English: The Barker Group primarily focuses on neurodegenerative disorders of the brain such as Parkinson’s disease (PD) and Huntington’s disease (HD). We have sought to better define the true extent of clinical deficits in these disorders with the aim of building a more complete model of disease heterogeneity and its basis which will then serve to inform on new therapies. This includes the translation of stem cell therapies to clinics by targeting the right sub-group of patients at the optimal stage of disease as well as other treatments such as drug repurposing- e.g. felodipine in HD.　

Research Focus: The Barker Group's main interests revolve around two relatively common, chronic neurodegenerative disorders of the nervous system - Parkinson’s disease (PD) and Huntington’s disease (HD). They are interested in better understanding how these diseases develop and then how they change over time with the idea of better classifying patients into different subtypes of disease. These subtypes can then be used to test new therapies as some types of these diseases may be better suited for one type of experimental treatment whilst others may not: e.g. dopamine cell therapies from stem cells treatment may be better suited to younger PD patients with a more benign clinical course.

The Barker Group is trying to better understand the brain pathology in these diseases through snRNA sequencing and post mortem tissue analysis in collaboration with Annelies Quaegebeur in Cambridge and Johan Jakobsson in Lund. They are looking to develop new treatments for PD and HD and are currently undertaking a drug repurposing trial in HD (FELL-HD) and a stem cell trial in PD (STEM-PD) with Lund University.

The lab also works with others to better understand normal development using human fetal samples. This has contributed to the human cell atlas as well as the development of new technologies and in particular this work has furthered our understanding of how the cells of the brain arise and organise themselves into structures, which has also helped better define cell types for transplantation.

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Dopaminergic neurons differentiated from embryonic stem cells using a clinical grade protocol and reagents—Tyrosine Hydroxylase (green), Beta III tubulin (red)

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Barker Group photo 

Key Publications

• Kirkeby A, Nelander J, ... Barker RA, Parmar M. Preclinical quality, safety, and efficacy of a human embryonic stem cell-derived product for the treatment of Parkinson’s disease, STEM-PD. Cell Stem Cell. 2023 Oct 5;30(10):1299-1314.e9. doi: 10.1016/j.stem.2023.08.014. PMID: 37802036
• Braun E, Danan-Gotthold M,... Barker RA, Arenas E, Sundström E, Linnarsson S. Comprehensive cell atlas of the first-trimester developing human brain. Science. 2023 Oct 13;382(6667):eadf1226. doi: 10.1126/science.adf1226. Epub 2023 Oct 13. PMID: 37824650
• Pircs K, Drouin-Ouellet J, Horváth V, Gil J, Rezeli M, Garza R, Grassi DA, Sharma Y, St-Amour I, Harris K, Jönsson ME, Johansson PA, Vuono R, Fazal SV, Stoker T, Hersbach BA, Sharma K, Lagerwall J, Lagerström S, Storm P, Hébert SS, Marko-Varga G, Parmar M, Barker RA, Jakobsson J. Distinct subcellular autophagy impairments in induced neurons from Huntington's disease patients. Brain. 2021 Dec 22:awab473. doi: 10.1093/brain/awab473. Epub ahead of print. PMID: 34936701.

• Barker RA, Cutting EV, Daft, DM. Bringing advanced therapy medicinal products (ATMPs) for Parkinson's Disease to the clinic: The investigator's perspective. J Parkinsons Dis. 2021;11(s2):S129-S134. doi: 10.3233/JPD-212563. PMID: 33814466; PMCID: PMC8543259.

• Haniffa M, Taylor D, Linnarsson S, Aronow BJ, Bader GD, Barker RA, Camara PG, Camp JG, Chédotal A, Copp A, Etchevers HC, Giacobini P, Göttgens B, Guo G, Hupalowska A, James KR, Kirby E, Kriegstein A, Lundeberg J, Marioni JC, Meyer KB, Niakan KK, Nilsson M, Olabi B, Pe'er D, Regev A, Rood J, Rozenblatt-Rosen O, Satija R, Teichmann SA, Treutlein B, Vento-Tormo R, Webb S; Human Cell Atlas Developmental Biological Network. A roadmap for the Human Developmental Cell Atlas. Nature. 2021 Sep;597(7875):196-205. doi: 10.1038/s41586-021-03620-1. Epub 2021 Sep 8. PMID: 34497388.

• Lovell-Badge R, Anthony E, Barker RA, Bubela T, Brivanlou AH, Carpenter M, Charo RA, Clark A, Clayton E, Cong Y, Daley GQ, Fu J, Fujita M, Greenfield A, Goldman SA, Hill L, Hyun I, Isasi R, Kahn J, Kato K, Kim JS, Kimmelman J, Knoblich JA, Mathews D, Montserrat N, Mosher J, Munsie M, Nakauchi H, Naldini L, Naughton G, Niakan K, Ogbogu U, Pedersen R, Rivron N, Rooke H, Rossant J, Round J, Saitou M, Sipp D, Steffann J, Sugarman J, Surani A, Takahashi J, Tang F, Turner L, Zettler PJ, Zhai X. ISSCR Guidelines for Stem Cell Research and Clinical Translation: The 2021 update. Stem Cell Reports. 2021 Jun 8;16(6):1398-1408. doi: 10.1016/j.stemcr.2021.05.012. Epub 2021 May 27. PMID: 34048692; PMCID: PMC8190668.

• Barker RA; TRANSEURO consortium. Designing stem-cell-based dopamine cell replacement trials for Parkinson's disease. Nature Medicine. 2019 Jul;25(7):1045-1053. PMID: 31263283

• Barker RA, Mason SL, Harrower TP, Swain RA, Ho AK, Sahakian BJ, Mathur R, Elneil S, Thornton S, Hurrelbrink C, Armstrong RJ, Tyers P, Smith E, Carpenter A, Piccini P, Tai YF, Brooks DJ, Pavese N, Watts C, Pickard JD, Rosser AE, Dunnett SB; the NEST-UK collaboration (2013). The long-term safety and efficacy of bilateral transplantation of human fetal striatal tissue in patients with mild to moderate Huntington's disease. J Neurol Neurosurg Psychiatry 84:657-65. PMCID:PMC3646287

• Clelland CD, Choi M, Romberg C, Clemenson GD Jr, Fragniere A, Tyers P, Jessberger S, Saksida LM, Gage FH*, Bussey TJ*, Barker RA*(2009). A functional role for adult hippocampal neurogenesis in spatial pattern separation. Science 325; 210-213. [*joint senior authors]. PMCID:PMC2997634

• Bocchi VD, Conforti P, Vezzoli E, Besusso D, Cappadona C, Lischetti T, Galimberti M, Ranzani V, Bonnal RJP, De Simone M, Rossetti G, He X, Kamimoto K, Espuny-Camacho I, Faedo A, Gervasoni F, Vuono R, Morris SA, Chen J, Felsenfeld D, Pavesi G, Barker RA, Pagani M, Cattaneo E.PMID: 33958447 Free article. The coding and long noncoding single-cell atlas of the developing human fetal striatum.

• Qarin S, Howlett SK, Jones JL, Barker RA..PMID: 34552761 Free PMC article. Review. The immunogenicity of midbrain dopaminergic neurons and the implications for neural grafting trials in Parkinson's disease.

• Skidmore S, Barker RA. PMID: 36635420 Review. Challenges in the clinical advancement of cell therapies for Parkinson's disease.

• Barker RA, Carpenter M, Jamieson CHM, Murry CE, Pellegrini G, Rao RC, Song J. PMID: 36563687 Free article. Review.  Lessons learnt, and still to learn, in first in human stem cell trials.