Basson Lab

King’s College, London

About

The Basson laboratory aims to understand how chromatin remodelling factors control brain development and function and how mutation of these factors cause neurodevelopmental disorders.

Our research will provide fundamental insights into the epigenetic mechanisms that underlie ataxia, developmental delay, autism, intellectual disability and executive dysfunction.

Mutations in CHD7 cause CHARGE syndrome, a syndrome that affects the development of multiple organs in the body. We have identified several critical roles for CHD7 in development of the cerebellum and our work has implicated CHD7 in cerebellar hypoplasia and medulloblastoma, the most common paediatric brain tumour. We are taking novel, unbiased approaches to identify cell type-specific distal regulatory elements that control and fine-tune the expression of key neurodevelopmental genes in the cerebellum, in order to identify non-coding substrates for neurodevelopmental disorders.

Mutations in CHD8 cause autism, macrocephaly and intellectual disability. We have identified key, dosage-dependent roles for CHD8 in regulating autism-associated genes and brain growth. CHD8 is recruited to the promoters of neurodevelopmental genes via the H3K4me3 epigenetic modification. Future work is focused on understanding the role of H3K4me3 in learning and memory.

Our research has been funded by the Medical Research Council, Simons Foundation Autism Research Initiative (SFARI), CHARGE syndrome Foundation and the Anatomical Society.

Albert Basson, PhD

Principal Investigator, Professor of Developmental Neurobiology

Albert obtained his PhD in Immunology from the University of Cambridge and underwent post-doctoral training at the National Institute for Medical Research (Mill Hill). He trained further in developmental biology and genetics as a Wellcome Trust International Research Fellow at Mount Sinai School of Medicine in New York, King’s College London and UCSF. His primary interest is to understand how deregulated cell signalling and gene expression results in congenital disease. His research has provided insights into the causes of developmental defects of the thymus, kidney, cardiovascular system and cerebellum. The current focus of his group is to uncover the function of chromatin remodelling factors in brain development and neurodevelopment disorders like autism.

Meet our team

Danielle Whittaker

Clinical Research Fellow (RVC and KCL)

Dani is a veterinary clinical research fellow, jointly funded by the Royal Veterinary College and King’s College London. After qualifying as a veterinary surgeon, Dani was awarded a highly competitive Wellcome Trust Integrated Training Fellowship for Veterinarians. She obtained her PhD and was board certified as a specialist clinical Neurologist. Dani’s research is focused on identifying novel genetic causes of neurodevelopmental disorders with cerebellar hypoplasia and understanding the mechanisms that control the specification and differentiation of GABAergic lineages in the cerebellum.


Leticia Perez Sisques

Post-doctoral research associate (MRC funded)

Leti joined us from the University of Barcelona in Spain where she obtained her PhD under the supervision of Cristina Malagelada Grau. Leti is investigating the function of chromatin remodelling factors in learning and memory in collaboration with Peter Giese in the Department of Basic and Clinical Neuroscience. She uses a combination of in vivo and molecular approaches to determine the functions of these factors in cognition and to determine if restoring function in the adult brain can rescue specific learning deficits. 


Shail Bhatt

PhD student (MRC DTP iCASE)

Shail joined the laboratory after completing his MSci degree at UCL. His PhD work will focus on characterising specific deficits in histone methylation machinery in neurons in the aged hippocampus and asking if correcting these deficits can ameliorate age-associated cognitive decline. 

This project is a collaboration between the Basson and Giese labs at KCL and an industrial partner, Merck, Sharp & Dohme. 


Andrew Graham

PhD student (Wellcome Trust Neuro-Immune Interactions in Health and Disease)

Andy obtained his BSc (Hons) in Physiology from the University of Edinburgh and joined us after completing an MSc in Neuroscience at UCL. He is interested in understanding how epigenetic changes that accumulate over time affect neuro-immune interactions in the aged hippocampus and lead to cognitive decline.

Andy is co-supervised by Paul Lavender in the Peter Gorer Department of Immunobiology.








Lab alumni

Alex Donovan (PhD, 2020): Post-doctoral fellow, Gurdon Institute, University of Cambridge
Rob Ellingford (PhD, 2020): Post-doctoral scientist, UCL
Talia Gileadi (PhD,2019): Post-doctoral scientist, UCL Institute of Neurology
Conor Mohan (PhD,2019): Scientific engagement manager, Seven Bridges
Shaun Hurley (PhD,2019) - Research scientist, Compass Pathways
Kimberley Riegman (PhD, 2019): Post-doctoral research fellow, Roche, SwitzerlandJohn Whittingham (Technician) - Publishing assistant, Springer Nature
Phil Suetterlin (Post-doc) - Physics teacher




Nemanja Saric (PhD, 2018) - Post-doc at Center for Neuroscience Research, Children's National Health System, Washington D.C. USA.
Sahrunizam Kasah (PhD, 2017) - Lecturer, Brunei Darussalam.Blanca Pijuan Sala (MSc, 2014) - PhD (Cantab); Post-doc at EMBL
Kieran Jones (PhD, 2013) - Analyst, KPMG.
Hagen Schmidt (Technician) - Technician, Barts and the London Cancer Centre.
Abigail Jackson (PhD, 2011) - Assistant Professor, Danish Stem Cell Institute, Copenhagen.
Subreena Simrick (Post-doc) - British Heart Foundation.
Jennifer Gardiner (PhD, 2010) - Editor, News & Views, Nature.


Projects

Currently there are four main research areas in the laboratory:

Functions and mechanisms of CHD7 in cerebellar and frontal cortex development

Neurodevelopmental roles of CHD8 and associated chromatin remodelling factors

Unbiased approaches to identify distal regulatory elements in primary cerebellar granule neuron progenitors

Chromatin regulation in learning and memory

Selected Publications


Ellingford, R.A., Panasiuk, M.J., Rabeshala De Meritens, E., Shaunak, R., Naybour, L., Browne, L., Basson, M.A.*, Andreae, L.C.* (2021) Cell-type-specific synaptic imbalance and disrupted homeostatic plasticity in cortical circuits of ASD-associated Chd8 haploinsufficient mice. Mol. Psych. in press *Joint corresponding authors 

Gileadi, T.E., Swamy, A.K., Hore, Z., Horswell, S., Ellegood, J., Mohan, C., Mizuno, K., Lundebye, A., Giese, K.P., Stockinger, B., Hogstrand, C., Lerch, J.P., Fernandes, C. & Basson, M.A. (2021) Low-dose gestational TCDD exposure disrupts behaviour, hippocampal neuron morphology and gene expression in mice. Environmental Health Perspectives. In press.

Badodi, S., Pomella, N., Zhang, X., Rosser, G., Whittingham, J., Niklison-Chirou, M.V., Lim, Y,M., Brandner, S., Morrison, G., Pollard, S.M., Bennett, C.D., Clifford, S.C., Peet, A., Basson, M.A. & Marino, S. (2021) Inositol treatment inhibits medulloblastoma through epigenetic-driven metabolic adaptation. Nat. Comms. 12:2148.


Hurley, S., Mohan, C., Suetterlin, P., Ellingford, R., Riegman, K.L.H., Ellegood, J., Caruso, A. , Michetti, C., Brock, O., Evans, R., Rudari, F., Delogu, A., Scattoni, M.L., Lerch, J.P., Fernandes, C. & Basson, M.A. (2021) Distinct, dosage-sensitive requirements for the autism-associated factor CHD8 during cortical development. Mol. Autism 12:16.

Kelly, E., Meng, F., Fujita, H., Morgado, F., Kazemi, Y., Rice, L.C., Ren, C., EsCamilla, C.O., Gibson, J.M., Sajadi, S., Pendry, R., Tan, T., Ellegood, J., Basson, M.A., Blakely, R.D., Dindot, S., Golzio, C., Hahn, M.K., Katsanis, N., Robins, D., Silvrman, J., Singh, K., Wevrick, R., Taylor, M., Hammill, C., Anagnostou, E., Pfeiffer, B.E., Stoodley, C.J., Lerch, J.P., du Lac, S. & Tsai, P.T. (2020) Regulation of autism-relevant behaviors by cerebellar-prefrontal cortical circuits. Nat. Neurosci. 23(9):1102-1110.

Sarić, N., Selby, M., Ramaswamy, V., Kool, M., Stockinger, B., Hogstrand, C., Williamson, D., Marino, S., Taylor, M.D., Clifford, S.C. & Basson, M.A. (2020) The AHR pathway represses TGFb-SMAD3 signalling and has a potent tumour suppressive role in SHH medulloblastoma. Sci. Reports 10(1):148.

Suetterlin P, Hurley S, Mohan C, Riegman KLH, Pagani M, Caruso A, Ellegood J, Galbusera A, Crespo-Enriquez I, Michetti C, Yee Y, Ellingford R, Brock O, Delogu A, Francis-West P, Lerch JP, Scattoni ML, Gozzi A, Fernandes C, Basson MA (2018) Altered Neocortical Gene Expression, Brain Overgrowth and Functional Over-Connectivity in Chd8 Haploinsufficient Mice. Cereb Cortex 28:2192-2206.

Whittaker, D.E., Riegman, K.L.H., Kasah, S., Mohan, C., Yu, T., Pijuan Sala, B., Hebaishi, H., Caruos, A., Marques, A.C., Michetti, C., Sanz Smachetti, M.E., Shah, A., Sabbioni, M., Kulhanci, O., Tee, W.W., Reinberg, D., Scattoni, M.L., Volk, H., McGonnell, I., Wardle, F., Fernandes, C. & Basson, M.A. (2017) The chromatin remodeling factor CHD7 controls cerebellar development by regulating reelin expression. J. Clin. Invest. Mar 1;127(3):874-887.

Basson, M.A. & van Ravenswaaij-Arts, C.M. (2015) Functional insights into chromatin remodelling from studies on CHARGE syndrome. Trends in Genetics 10:600-611.

Yu, T., Meiners, L.C., Danielsen, K., Wong, T.Y., Bowler, T., Reinberg, D., Scambler, P.J., van Ravenswaaij, C.M.A. & Basson, M.A. (2013) Deregulated FGF and homeotic gene expression underlies cerebellar vermis hypoplasia in CHARGE syndrome. eLife 2:e01305.

Chakkalakal, J., Jones, K., Basson, M.A. & Brack, A.S. (2012) The aged niche disrupts muscle stem cell quiescence. Nature 490:355-360.

All Publications