Tuschl Group

Dr Karin Tuschl is an MRC Clinician Scientist Fellow and group leader at the UCL Great Ormond Street Institute of Child Health, and Honorary Consultant in Paediatric Metabolic Medicine at Great Ormond Street Hospital for Children. She specialises in genetic disorders associated with metal dyshomeostasis.

Inherited Manganese Transporter Defects

Manganese is an essential trace metal and critical for brain physiology and development. However, excess manganese is neurotoxic and leads to dystonia-parkinsonism, psychiatric and intellectual impairments.

Our research has identified two manganese transporter defects associated with manganese neurotoxicity – hypermanganesaemia with dystonia 1 (HMNDYT1) and 2 (HMNDYT2). They are caused by loss-of-function mutations in SLC30A10 and SLC39A14, respectively, that encode manganese transporters that act in conjunction to mediate metal excretion. Manganese deposition in the brain leads to progressive, childhood-onset dystonia-parkinsonism associated with significant disability and premature death.

Our lab uses manganese transporter mutant zebrafish and mouse models of manganese overload/deficiency in order to dissect how metal dyshomeostasis disrupts neurons, synapses and circuit function with the view to identifying new therapeutic targets. In addition, we are working to develop a novel, orally bioavailable Mn chelator as well as mRNA therapies to improve treatment for disorders associated with Mn neurotoxicity. Our lab is part of Zebrafish research at UCL that provides an exceptional collaborative environment unique to UCL.

Collaborators

• Prof Stephen Wilson, Department of Cell and Developmental Biology, UCL
• Prof Ahad Rahim, School of Pharmacy, UCL
• Prof Andrey Abramov, Institute of Neurology, UCL
• Prof John Spencer, Department of Chemistry, University of Sussex 
• Prof Philip Blower, Department of Imaging Chemistry and Biology, KCL
• Prof Susanne Greber-Platzer, Medical University of Vienna, Austria
• Prof Giulio Superti-Furga, Centre for Molecular Medicine, Vienna, Austria

Funders

• 2024 GOSHCC Liftoff Discovery Grant
• 2023 UCL Therapeutic Acceleration Support Fund Rare Diseases Call
• 2023 Action Medical Research Project Grant
• 2022 NIHR GOSH BRC Junior Faculty Consumable Grant
• 2021 UCL Small Molecules TIN Pilot Data Scheme
• 2021 UCL Accelerate Innovation Team Challenge – Team AccessBrain
• 2021 MRC Clinician Scientist Fellowship
• 2017 GOSHCC Clinical Research Starter Grant
• 2017 Starter Grant for Clinical Lecturers, Academy of Medical Sciences
• 2016 UCL Neuroscience ZNZ Collaboration
• 2012 Action Medical Research – Research Training Fellowship

Selected Publications

• Alba-González A, Dragomir EI, Haghdousti G, Yáñez J, Dadswell C, González-Méndez R, Wilson SW, Tuschl K, Folgueira M. Manganese Overexposure Alters Neurogranin Expression and Causes Behavioral Deficits in Larval Zebrafish. Int J Mol Sci. 2024;25(9):4933. doi: 10.3390/ijms25094933.
• Tuschl K, White RJ, Trivedi C, Valdivia LE, Niklaus S, Bianco IH, Dadswell C, González-Méndez R, Sealy IM, Neuhauss SCF, Houart C, Rihel J, Wilson SW, Busch-Nentwich EM. Loss of slc39a14 causes simultaneous manganese hypersensitivity and deficiency in zebrafish. Dis Model Mech. 2022;15(6):dmm044594. doi: 10.1242/dmm.044594.
• Taylor CA, Tuschl K, Nicolai MM, Bornhorst J, Gubert P, Varão AM, Aschner M, Smith DR, Mukhopadhyay S. Maintaining Translational Relevance in Animal Models of Manganese Neurotoxicity. J Nutr. 2020;150(6):1360-1369. doi: 10.1093/jn/nxaa066.
• Anagianni S, Tuschl K. Genetic Disorders of Manganese Metabolism. Curr Neurol Neurosci Rep. 2019;19(6):33. doi: 10.1007/s11910-019-0942-y.
• Yapici Z, Tuschl K, Eraksoy M. Hypermanganesemia with Dystonia 1: A Novel Mutation and Response to Iron Supplementation. Mov Disord Clin Pract. 2019;7(1):94-96. doi: 10.1002/mdc3.12861.
• Tuschl K, Meyer E, Valdivia LE, Zhao N, Dadswell C, Abdul-Sada A, Hung CY, Simpson MA, Chong WK, Jacques TS, Woltjer RL, Eaton S, Gregory A, Sanford L, Kara E, Houlden H, Cuno SM, Prokisch H, Valletta L, Tiranti V, Younis R, Maher ER, Spencer J, Straatman-Iwanowska A, Gissen P, Selim LA, Pintos-Morell G, Coroleu-Lletget W, Mohammad SS, Yoganathan S, Dale RC, Thomas M, Rihel J, Bodamer OA, Enns CA, Hayflick SJ, Clayton PT, Mills PB, Kurian MA, Wilson SW. Mutations in SLC39A14 disrupt manganese homeostasis and cause childhood-onset parkinsonism-dystonia. Nat Commun. 2016;7:11601. doi: 10.1038/ncomms11601.
• Tuschl K, Mills PB, Clayton PT. Manganese and the brain. Int Rev Neurobiol. 2013;110:277-312. doi: 10.1016/B978-0-12-410502-7.00013-2.
• Tuschl K, Clayton PT, Gospe SM Jr, Gulab S, Ibrahim S, Singhi P, Aulakh R, Ribeiro RT, Barsottini OG, Zaki MS, Del Rosario ML, Dyack S, Price V, Rideout A, Gordon K, Wevers RA, Chong WK, Mills PB. Syndrome of hepatic cirrhosis, dystonia, polycythemia, and hypermanganesemia caused by mutations in SLC30A10, a manganese transporter in man. Am J Hum Genet. 2012 Mar 9;90(3):457-66. doi: 10.1016/j.ajhg.2012.01.018. Epub 2012 Feb 16. Erratum in: Am J Hum Genet. 2016;99(2):521. doi: 10.1016/j.ajhg.2016.07.015.
• Tuschl K, Mills PB, Parsons H, Malone M, Fowler D, Bitner-Glindzicz M, Clayton PT. Hepatic cirrhosis, dystonia, polycythaemia and hypermanganesaemia--a new metabolic disorder. J Inherit Metab Dis. 2008;31(2):151-63. doi: 10.1007/s10545-008-0813-1.

Principal Investigator

Dr Karin Tuschl - UCL Profiles page

Contact us

Inborn Errors of Metabolism Section
UCL Great Ormond Street Institute of Child Health
30 Guilford Street
London
WC1N 1EH 

Useful Links

Zebra Fish UCL