Dr Kathryn Bowles

Personal profile

• 09/2022 – present: Group Leader, UK DRI centre at the University of Edinburgh, UK
• 05/2019 – 08/2022: Instructor, Genetics and Genomics, Icahn School of Medicine at Mount Sinai, NY, USA
• 03/2015 – 04/2019: Postdoctoral fellow, Neuroscience, Icahn School of Medicine at Mount Sinai, NY, USA
• 09/2014 – 03/2015: Postdoctoral fellow, Neuroscience, Cardiff University, UK
• 09/2010 – 08/2014: PhD in Integrative Neuroscience, Cardiff University, UK
• 09/2005 – 07/2008: BSc. Hons in Psychology and Cognitive Neuroscience, University of Nottingham, UK

Research

My primary interest is in understanding the genetic and mechanistic biology underlying Tauopathy. In particular, I find it fascinating that multiple neurodegenerative diseases are associated with altered tau processing and accumulation, while encompassing a diverse array of neuropathological and clinical phenotypes. The MAPT locus has also been genetically associated with other neurodegenerative diseases that are not characterized by the presence of tau pathology, such as Parkinson’s disease. We are using a combination of functional genomics, biochemical and cell culture approaches to investigate the mechanisms underlying the regulation of MAPT expression, function and splicing. This knowledge forms the basis for understanding how these processes are dysregulated in, and contribute to Alzheimer’s disease, progressive supranuclear palsy, Parkinson’s disease and multiple other tauopathies. We also employ genome editing techniques in iPSC lines in order to generate more accurate iPSC-derived models of tauopathy in order to better characterize neuronal and glial phenotypes associated with aberrant tau splicing, phosphorylation and aggregation. Our work aims to understand the biological mechanisms underlying multiple tauopathies, with a focus on cellular stress, synaptic biology and neuronal-glial interactions.

Funding

• UK DRI
• BrightFocus Foundation
• Parkinson's UK
• Rainwater Charitable Foundation
• CurePSP
• Royal Society

Team members

• Dr. Filipa Henderson-Sousa (postdoc)
• Dr. Dianne Lopez (postdoc)
• Kathryn Newton (senior technician)
• Lois Keavey (research assistant)

Publications

Novel avenues of tau research: Sexton CE, Bitan G, Bowles KR, Brys M, Buée L, Maina MB, Clelland CD, Cohen AD, Crary JF, Dage JL, Diaz K, Frost B, Gan L, Goate AM, Golbe LI, Hansson O, Karch CM, Kolb HC, La Joie R, Lee SE, Matallana D, Miller BL, Onyike CU, Quiroz YT, Rexach JE, Rohrer JD, Rommel A, Sadri-Vakili G, Schindler SE, Schneider JA, Sperling RA, Teunissen CE, Weninger SC, Worley SL, Zheng H, Carrillo MC. Alzheimer's and Dementia 2024. doi: 10.1002/alz.13533

Improved protocol for reproducible human cortical organoids reveals early alterations in metabolism with MAPT mutations: Bertucci T, Bowles KR, Lotz S, Qi L, Stevens K, Goderie SK, Borden S, Oja LM, Lane K, Lotz R, Lotz H, Chowdhury R, Joy S, Arduini BL, Butler DC, Miller M, Baron H, Sandhof CA, Silva MC, Haggarty SJ, Karch CM, Geschwind DH, Goate AM, Temple S. bioRxiv 2023. doi: 10.1101/2023.07.11.548571

Development of MAPT S305 mutation models exhibiting elevated 4R tau expression, resulting in altered neuronal and astrocytic function: Bowles KR, Pugh DA, Pedicone C, Oja L-M, Weitzman SA, Liu Y, Chen JL, Disney MD, Goate AM. bioRxiv 2023. doi: 10.1101/2023.06.02.543224

Mutations in α-synuclein, TDP-43 and tau prolong protein half-life through diminished degradation by lysosomal proteases: Sampognaro PJ, Arya S, Knudsen GM, Gunderson EL, Sandoval-Perez A, Hodul M, Bowles KR, Craik CS, Jacobson MP, Kao AW. Mol Neurodegener. 2023. doi: 10.1186/s13024-023-00621-8

The influence of 17q21.31 and APOE genetic ancestry on neurodegenerative disease risk: Harerimana NV, Goate AM, Bowles KR. Front Aging Neurosci. 2022. doi: 10.3389/fnagi.2022.1021918

17q21.31 sub-haplotypes underlying H1-associated risk for Parkinson's disease are associated with LRRC37A/2 expression in astrocytes: Bowles KR, Pugh DA, Liu Y, Patel T, Renton AE, Bandres-Ciga S, Gan-Or Z, Heutink P, Siitonen A, Bertelsen S, Cherry JD, Karch CM, Frucht SJ, Kopell BH, Peter I, Park YJ, Charney A, Raj T, Crary JF, Goate AM. Mol Neurodegener. 2022. doi: 10.1186/s13024-022-00551-x.

Dysregulated coordination of MAPT exon 2 and exon 10 splicing underlies different tau pathologies in PSP and AD: Bowles KR, Pugh DA, Oja LM, Jadow BM, Farrell K, Whitney K, Sharma A, Cherry JD, Raj T, Pereira AC, Crary JF, Goate AM. Acta Neuropathol. 2022. doi: 10.1007/s00401-021-02392-2.

Genome-wide association study and functional validation implicates JADE1 in tauopathy: Farrell K, Kim S, Han N, Iida MA, Gonzalez EM, Otero-Garcia M, Walker JM, Richardson TE, Renton AE, Andrews SJ, Fulton-Howard B, Humphrey J, Vialle RA, Bowles KR, de Paiva Lopes K, Whitney K, Dangoor DK, Walsh H, Marcora E, Hefti MM, Casella A, Sissoko CT, Kapoor M, Novikova G, Udine E, Wong G, Tang W, Bhangale T, Hunkapiller J, Ayalon G, Graham RR, Cherry JD, Cortes EP, Borukov VY, McKee AC, Stein TD, Vonsattel JP, Teich AF, Gearing M, Glass J, Troncoso JC, Frosch MP, Hyman BT, Dickson DW, Murray ME, Attems J, Flanagan ME, Mao Q, Mesulam MM, Weintraub S, Woltjer RL, Pham T, Kofler J, Schneider JA, Yu L, Purohit DP, Haroutunian V, Hof PR, Gandy S, Sano M, Beach TG, Poon W, Kawas CH, Corrada MM, Rissman RA, Metcalf J, Shuldberg S, Salehi B, Nelson PT, Trojanowski JQ, Lee EB, Wolk DA, McMillan CT, Keene CD, Latimer CS, Montine TJ, Kovacs GG, Lutz MI, Fischer P, Perrin RJ, Cairns NJ, Franklin EE, Cohen HT, Raj T, Cobos I, Frost B, Goate A, White Iii CL, Crary JF. Acta Neuropathol. 2022. doi: 10.1007/s00401-021-02379-z.

ELAVL4, splicing, and glutamatergic dysfunction precede neuron loss in MAPT mutation cerebral organoids: Bowles KR, Silva MC, Whitney K, Bertucci T, Berlind JE, Lai JD, Garza JC, Boles NC, Mahali S, Strang KH, Marsh JA, Chen C, Pugh DA, Liu Y, Gordon RE, Goderie SK, Chowdhury R, Lotz S, Lane K, Crary JF, Haggarty SJ, Karch CM, Ichida JK, Goate AM, Temple S. Cell. 2021. doi: 10.1016/j.cell.2021.07.003.

Alzheimer's-associated PU.1 expression levels regulate microglial inflammatory response: Pimenova AA, Herbinet M, Gupta I, Machlovi SI, Bowles KR, Marcora E, Goate AM. Neurobiol Dis. 2021. doi: 10.1016/j.nbd.2020.105217.

Cell Type-Specific In Vitro Gene Expression Profiling of Stem Cell-Derived Neural Models: Gregory JA, Hoelzli E, Abdelaal R, Braine C, Cuevas M, Halpern M, Barretto N, Schrode N, Akbalik G, Kang K, Cheng E, Bowles KR, Lotz S, Goderie S, Karch CM, Temple S, Goate A, Brennand KJ, Phatnani H. Cells. 2020. doi: 10.3390/cells9061406 .

A Comprehensive Resource for Induced Pluripotent Stem Cells from Patients with Primary Tauopathies: Karch CM, Kao AW, Karydas A, Onanuga K, Martinez R, Argouarch A, Wang C, Huang C, Sohn PD, Bowles KR, Spina S, Silva MC, Marsh JA, Hsu S, Pugh DA, Ghoshal N, Norton J, Huang Y, Lee SE, Seeley WW, Theofilas P, Grinberg LT, Moreno F, McIlroy K, Boeve BF, Cairns NJ, Crary JF, Haggarty SJ, Ichida JK, Kosik KS, Miller BL, Gan L, Goate AM, Temple S. Stem Cell Reports. 2019. doi: 10.1016/j.stemcr.2019.09.006 .

Reduced variability of neural progenitor cells and improved purity of neuronal cultures using magnetic activated cell sorting: Bowles KR, TCW J, Qian L, Jadow BM, Goate AM. PLoS One. 2019. doi: 10.1371/journal.pone.0213374 .

High-resolution temporal and regional mapping of MAPT expression and splicing in human brain development: Hefti MM, Farrell K, Kim S, Bowles KR, Fowkes ME, Raj T, Crary JF. PLoS One. 2018. doi: 10.1371/journal.pone.0195771 .

An Efficient Platform for Astrocyte Differentiation from Human Induced Pluripotent Stem Cells: TCW J, Wang M, Pimenova AA, Bowles KR, Hartley BJ, Lacin E, Machlovi SI, Abdelaal R, Karch CM, Phatnani H, Slesinger PA, Zhang B, Goate AM, Brennand KJ. Stem Cell Reports. 2017. doi: 10.1016/j.stemcr.2017.06.018.

SMAD transcription factors are altered in cell models of HD and regulate HTT expression: Bowles KR, Stone T, Holmans P, Allen ND, Dunnett SB, Jones L. Cell Signal. 2017. doi: 10.1016/j.cellsig.2016.12.005 .

Huntingtin Subcellular Localisation Is Regulated by Kinase Signalling Activity in the StHdhQ111 Model of HD: Bowles KR, Brooks SP, Dunnett SB, Jones L. PLoS One. 2015. doi: 10.1371/journal.pone.0144864 .

Kinase signalling in Huntington's disease: Bowles KR, Jones L. J Huntingtons Dis. doi: 10.3233/JHD-140106 .

Gene expression and behaviour in mouse models of HD: Bowles KR, Brooks SP, Dunnett SB, Jones L. Brain Res Bull. 2012. doi: 10.1016/j.brainresbull.2011.07.021.

Information for students:

Willingness to discuss research projects with undergraduate and postgraduate students: YES - Please click here: