Dr Mariah Lelos
Research Associate
- lelosmj@cardiff.ac.uk
- +44 (0)29 2087 5541
- Cardiff School of Biosciences, The Sir Martin Evans Building, Museum Avenue, Cardiff, CF10 3AX, Adeilad Syr Martin Evans, Rhodfa'r Amgueddfa, Caerdydd, CF10 3AX
- Ar gael fel goruchwyliwr ôl-raddedig
Trosolwg
I am the Associate Theme Lead for Mind, Brain and Neurosciences.
Animal Welfare and Research Panel (AWARP).
Bywgraffiad
My PhD (2005-2010, Prof M Good) investigated neural network dysfunction using mathematical modelling in a mouse model of Alzheimer's disease, with a particular focus on amyloid-induced amydala and hippocampal dysfunction.
My post-doctoral research (2010-2015, Prof S Dunnett) aimed to understand basal ganglia dysfunction in Parkinson's and Huntington's disease and to explore the use of human fetal and novel stem cell derived therapies to alleviate the behavioural impairments.
I was then awarded a Senior Research Fellowship from Parkinson's UK (2015-2018) to investigate the ability of human stem cell derived cell therapy products to ameliorate cognitive impairments in rodent models of Parkinson's disease.
I have recently commenced a Senior Lectureship in the neuroscience department and my lab is exploring several new avenues. We are seeking to understand the mechanisms of neural dysfunction using novel DREADDs manipulations, undertaking PET/MR imaging and using newly created models of disease. We are also studying the impact of novel cell therapy approaches and newly optimised gene therapies on cellular and behavioural function.
Cyhoeddiadau
2022
- Sap, J. B. I. et al. 2022. [18F]Difluorocarbene for Positron Emission Tomography. Nature 606, pp. 102-108. (10.1038/s41586-022-04669-2)
- Lelos, M. J. 2022. Can cell and gene therapies improve cognitive symptoms in Parkinson's disease?. Journal of Integrative Neuroscience 21(3), article number: 78. (10.31083/j.jin2103078)
- Lane, E. L., Harrison, D. J., Ramos-Varas, E., Hills, R., Turner, S. and Lelos, M. J. 2022. Spontaneous graft-induced dyskinesias are independent of 5-HT neurons and levodopa priming in a model of Parkinson's disease. Movement Disorders 37(3), pp. 613-619. (10.1002/mds.28856)
2021
- Bartley, O. J. M., Lelos, M. J., Gray, W. P. and Rosser, A. E. 2021. Do foetal transplant studies continue to be justified in Huntington's disease?. Neuronal Signaling 5, article number: acerbic. (10.1042/NS20210019)
2020
- Lelos, M. 2020. Overview of Alzheimer's and Parkinson's diseases and the role of protein aggregation in these neurodegenerative diseases. In: Salgado, A. J. ed. Handbook of Innovations in Central Nervous System Regenerative Medicine. Elsevier, pp. 29-53., (doi.org/10.1016/B978-0-12-818084-6.00002-7)
2018
- Lelos, M. J. and Dunnett, S. B. 2018. Generating excitotoxic lesion models of Huntington’s Disease. In: Precious, S. V., Rosser, A. E. and Dunnett, S. B. eds. Huntington’s Disease. Methods in Molecular Biology New York, NY, USA:, pp. 209-220., (10.1007/978-1-4939-7825-0_11)
- Clinch, S. P., Busse, M., Lelos, M. J. and Rosser, A. E. 2018. Rethinking functional outcome measures: the development of an upper limb test to assess basal ganglia dysfunction. Frontiers in Neuroscience 12, article number: 366. (10.3389/fnins.2018.00366)
2017
- Kirkeby, A. et al. 2017. Predictive markers guide differentiation to improve graft outcome in clinical translation of hESC-based therapy for Parkinson's disease. Cell Stem Cell 20(1), pp. 135-148. (10.1016/j.stem.2016.09.004)
2016
- Yhnell, E., Lelos, M. J., Dunnett, S. B. and Brooks, S. P. 2016. L30 Cognitive training improves disease symptoms in a mouse model of huntington's disease. Journal of Neurology, Neurosurgery & Psychiatry 87(Supp 1), pp. A100-A101. (10.1136/jnnp-2016-314597.285)
- Yhnell, E., Lelos, M. J., Dunnett, S. B. and Brooks, S. P. 2016. Cognitive training modifies disease symptoms in a mouse model of Huntington's disease. Experimental Neurology 282, pp. 19-26. (10.1016/j.expneurol.2016.05.008)
- Lelos, M. J. et al. 2016. Direct comparison of rat- and human-derived ganglionic eminence tissue grafts on motor function. Cell Transplantation 25, pp. 665-675. (10.3727/096368915X690297)
- Lelos, M., Morgan, R. J., Kelly, C., Torres, E. M., Rosser, A. E. and Dunnett, S. B. 2016. Amelioration of non-motor dysfunctions after transplantation of human dopamine neurons in a model of Parkinson's disease. Experimental Neurology 278, pp. 54-61. (10.1016/j.expneurol.2016.02.003)
- Harvey, A. K. et al. 2016. Novel application of behavioral assays allows dissociation of joint pathology from systemic extra-articular alterations induced by inflammatory arthritis. Journal of Rheumatic Diseases and Treatment 2(2), article number: 33. (10.23937/2469-5726/1510033)
2014
- Lelos, M. J. and Good, M. A. 2014. β-Amyloid pathology alters neural network activation during retrieval of contextual fear memories in a mouse model of Alzheimer's disease. European Journal of Neuroscience 39(10), pp. 1690-1703. (10.1111/ejn.12527)
2013
- Murphy, E. M., Lelos, M. J., O'Neill, M. J., Lane, E. L. and Dunnett, S. B. 2013. Long-term restorative effects of bromocriptine on operant responding in the 6-hydroxydopamine-lesioned rat. NeuroReport 24(18), pp. 1019-1024. (10.1097/WNR.0000000000000060)
- Heuer, A., Lelos, M. J., Kelly, C., Torres, E. M. and Dunnett, S. B. 2013. Dopamine-rich grafts alleviate deficits in contralateral response space induced by extensive dopamine depletion in rats. Experimental Neurology 247, pp. 485-495. (10.1016/j.expneurol.2013.01.020)
- Lelos, M. J., Lane, E. and Dunnett, S. B. 2013. What helps can also hinder: A dissociation in the acute effect of levodopa treatment on motor and cognitive functions. Movement Disorders 28(5), pp. 563-564. (10.1002/mds.25294)
- Carri, A. D. et al. 2013. Developmentally coordinated extrinsic signals drive human pluripotent stem cell differentiation toward authentic DARPP-32(+) medium-sized spiny neurons. Development 140(2), pp. 301-312. (10.1242/dev.084608)
- Lelos, M. J., Harrison, D. J., Rosser, A. E. and Dunnett, S. B. 2013. The lateral neostriatum is necessary for compensatory ingestive behaviour after intravascular dehydration in female rats. Appetite 71, pp. 287-294. (10.1016/j.appet.2013.09.003)
- Trueman, R. C., Klein, A., Lindgren, H. S., Lelos, M. J. and Dunnett, S. B. 2013. Repair of the CNS using endogenous and transplanted neural stem cells. Current Topics in Behavioural Neurosciences 15, pp. 357-398. (10.1007/7854_2012_223)
2012
- Lelos, M. J., Harrison, D. J. and Dunnett, S. B. 2012. Intrastriatal excitotoxic lesion or dopamine depletion of the neostriatum differentially impairs response execution in extrapersonal space. European Journal of Neuroscience 36(10), pp. 3420-3428. (10.1111/j.1460-9568.2012.08256.x)
- Lindgren, H. S., Lelos, M. J. and Dunnett, S. B. 2012. Do alpha-synuclein vector injections provide a better model of Parkinson's disease than the classic 6-hydroxydopamine model?. Experimental Neurology 237(1), pp. 36-42. (10.1016/j.expneurol.2012.05.022)
- Lelos, M. J. and Good, M. A. 2012. c-Fos expression reveals aberrant neural network activity during cued fear conditioning in APPswe transgenic mice. Neurobiology of Learning and Memory 98(1), pp. 1-11. (10.1016/j.nlm.2012.03.001)
- Dunnett, S. B., Heuer, A., Lelos, M. J., Brooks, S. P. and Rosser, A. E. 2012. Bilateral striatal lesions disrupt performance in an operant delayed reinforcement task in rats. Brain Research Bulletin 88(2-3), pp. 251-260. (10.1016/j.brainresbull.2011.04.002)
- Heuer, A., Smith, G. A., Lelos, M. J., Lane, E. L. and Dunnett, S. B. 2012. Unilateral nigrostriatal 6-hydroxydopamine lesions in mice I: Motor impairments identify extent of dopamine depletion at three different lesion sites. Behavioural Brain Research 228(1), pp. 30-43. (10.1016/j.bbr.2011.11.027)
- Lelos, M. J., Dowd, E. and Dunnett, S. B. 2012. Nigral grafts in animal models of Parkinson's disease. Is recovery beyond motor function possible?. In: Progress in Brain Research., Vol. 200. Elsevier, pp. 113-142., (10.1016/B978-0-444-59575-1.00006-5)
2011
- Thomas, R. S., Lelos, M. J., Good, M. A. and Kidd, E. J. 2011. Clathrin-mediated endocytic proteins are upregulated in the cortex of the Tg2576 mouse model of Alzheimer's disease-like amyloid pathology. Biochemical and Biophysical Research Communications 415(4), pp. 656-661. (10.1016/j.bbrc.2011.10.131)
- Lelos, M. J., Harrison, D. J. and Dunnett, S. B. 2011. Impaired sensitivity to Pavlovian stimulus-outcome learning after excitotoxic lesion of the ventrolateral neostriatum. Behavioural Brain Research 225(2), pp. 522-528. (10.1016/j.bbr.2011.08.017)
- Lelos, M. J., Thomas, R. S., Kidd, E. J. and Good, M. A. 2011. Outcome-specific satiety reveals a deficit in context-outcome, but not stimulus-or action-outcome, associations in aged Tg2576 mice. Behavioral Neuroscience 125(3), pp. 412-425. (10.1037/a0023415)
- Lelos, M. J. and Dunnett, S. B. 2011. Aberrant dopamine transmission and cognitive dysfunction in animal models of Parkinson's disease. Journal of Parkinson's Disease 1(2), pp. 151-165.
2010
- Dunnett, S. B. and Lelos, M. 2010. Behavioural analysis of motor and non-motor symptoms in rodent models of Parkinson’s disease. In: Progress in Brain Research., Vol. 184. Elsevier, pp. 35-51., (10.1016/S0079-6123(10)84003-8)
- Lelos, M. J. 2010. Influence of beta-amyloid pathology on emotional learning and memory in the APPswe model of Alzheimer's disease. PhD Thesis, Cardiff University.
Addysgu
I am currently the Assessment Lead on 3rd year module Neurobiology of Brain Disorders and I teach on the Cellular and Molecular Biology module at Master's level. I run practicals to teach histological and immunohistochemical assays and microscopy skills using rodent brain tissues.
I am a personal tutor for Neuroscience and Biomedical undergraduate students.
My lab focuses on understanding and treating neurodegenerative diseases, particularly Parkinson’s and Huntington’s diseases. We are interested in understanding the manifestation of motor and non-motor (cognitive, neuropsychiatric) dysfunctions in degenerative diseases using lesion, viral vector and genetically modified rodent models. We are also investigating the ability of novel cell (hESC- and hiPSC-derived) and gene therapies to alleviate these impairments and optimising these treatments for clinical application.
Some current research questions that are being addressed include:
Can hPSC-derived dopamine grafts alleviate non-motor dysfunctions in Parkinson's disease?
Is Pax6 a useful biomarker of transplant maturation and efficacy?
Does neuroinflammation play a role in hPSC-derived dopmine graft-induced dyskinesias?
What is the impact of dopamine production from AAV vectors on striatal-dependent cognitive function?
Can we modulate gene expression to improve neurite outgrowth and synapse formation from hPSC-derived dopamine grafts?
Can hPSC-derived medium spiny neuron transplants form synaptic connections and alleviate non-motor dysfunctions in models of Huntingtons' disease?
Supervision
I am keen to welcome new PhD students to the team with a particular interest in:
Parkinson's disease
Huntington's disease
Cognitive or neuropsychiatric dysfunctions
Cell therapies
Gene therapies
