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Dr Dan Berwick

Dr Dan Berwick

Profile summary

  • Visiting Informal Academic
  • Visiting Fellow
  • Faculty of Science, Technology, Engineering & Mathematics
  • School of Life, Health & Chemical Sciences

Web links

Professional biography

I am a molecular neuroscientist with a broad training and a wide range of scientific interests. I moved to the OU in April 2015 and am currently setting-up my lab.

I began my career with a BSc in Medical Biochemistry at The University of Leicester, UK (1995-1998), followed by an MSc in International Biotechnology taught jointly by De Montfort University, UK, and the Hogeschool Brabant, the Netherlands (1998-1999). I subsequently undertook a PhD in at the University of Bristol, UK (1999-2003). I also hold a Graduate Certificate in Statistics obtained part-time from Birkbeck, University of London (2009-2010). My first post-doc was at Columbia University, USA (2003-2005), studying the molecular mechanisms of learning and memory. This was followed by posts at the UCL Institute of Child Health, UK (2006-2009), investigating gene expression and neurogenesis, and The School of Pharmacy (now UCL School of Pharmacy), UK (2009-2015), studying the role of deregulated Wnt signalling in the aetiology of Parkinson’s disease.

Research interests

The long-term aim for my research is to develop and utilize state-of-the-art cellular models to study Parkinson’s disease (PD). PD is an incurable neurodegenerative disease that greatly decreases the quality of life of its sufferers and of their families. I am most interested in uncovering the earliest molecular events occurring in this condition, which happen before neurons have died and diagnosable symptoms are present. Targeting these events represents the only realistic non-surgical approach to curing the disease.

My recent work has focused on Leucine-rich repeat kinase 2 (LRRK2). Although PD risk is predominantly conferred by environmental factors, mutations in the LRRK2 gene are the most common known cause of PD. Working with Kirsten Harvey at the UCL School of Pharmacy, I have found strong evidence that LRRK2 plays a role in the canonical Wnt signaling pathway. Most importantly, PD-causing mutations in LRRK2 weaken Wnt signaling, whilst our soon-to-be-published data indicate that a protective mutation has the opposite effect, increasing the strength of this signal transduction pathway. These results are remarkable given the growing number of genes linked to both PD and the canonical Wnt pathway (e.g. LRRK2, Parkin, VPS35 and others). Furthermore, the evidence for a key role for Wnt signaling for the normal functioning and survival of cells in a healthy brain is accumulating all the time. Thus my work is at the forefront of an exciting story that implicates deregulated Wnt signaling in the pathology of PD.

I am currently setting up my lab at the OU with two major focuses: 1) research into the effect of PD-causing mutations and environmental factors on Wnt signaling; 2) the use of unbiased comparative approaches to determine common consequences of PD-causing mutations. Beyond these, I have a wide range of interests including the application of mathematics to biology, cell signaling and kinase biology, gene transcription and vesicle trafficking. I am also interested in other forms of neurological disease, for example Alzheimer’s disease, Huntington’s disease, and Schizophrenia.

Impact and engagement

I am keen to present my work to academic colleagues and lay people alike, and also to engage with Journalists and media professionals to enhance the impact of my work. For example, coverage of results I presented at the Society for Neuroscience conference in New Orleans in 2012 were covered in the online Alzheimer’s disease magazine, Alzforum. 

Publications

Downregulated Wnt/β-catenin signalling in the Down syndrome hippocampus (2019-05-13)
Granno, Simone; Nixon-Abell, Jonathon; Berwick, Daniel; Tosh, Justin; Heaton, George; Almudimeegh, Sultan; Nagda, Zenisha; Rain, Jean-Christophe; Zanda, Manuela; Plagnol, Vincent; Tybulewicz, Victor L. J.; Cleverley, Karen; Wiseman, Frances K.; Fisher, Elizabeth M. C. and Harvey, Kirsten
Scientific Reports, 9, Article 7322

LRRK2 Biology from structure to dysfunction: research progresses, but the themes remain the same (2019)
Berwick, Daniel C.; Heaton, George R.; Azeggagh, Sonia and Harvey, Kirsten
Molecular neurodegeneration, 14, Article 49

The relevance of α-KLOTHO to the central nervous system: Some key questions (2017-07)
Cararo-Lopes, Marina Minto; Mazucanti, Caio Henrique Yokoyama; Scavone, Cristoforo; Kawamoto, Elisa Mitiko and Berwick, Daniel Charles
Ageing Research Reviews, 36 (pp. 137-148)

Pathogenic LRRK2 variants are gain-of function mutations that enhance LRRK2-mediated repression of β-catenin signaling (2017-01-19)
Berwick, Daniel C.; Javaheri, Behzad; Wetzel, Andrea; Hopkinson, Mark; Nixon-Abell, Jonathon; Granno, Simone; Pitsillides, Andrew A. and Harvey, Kirsten
Molecular Neurodegeneration, 12, Article 9

Protective LRRK2 R1398H Variant Enhances GTPase and Wnt Signaling Activity (2016-03-08)
Nixon-Abell, Jonathon; Berwick, Daniel C.; Granno, Simone; Spain, Victoria A.; Blackstone, Craig and Harvey, Kirsten
Frontiers in Molecular Neuroscience, 9, Article 18

The regulation and deregulation of Wnt signaling by PARK genes in health and disease (2014-02)
Berwick, Daniel C. and Harvey, Kirsten
Journal of Molecular Cell Biology, 6(1) (pp. 3-12)

A Direct Interaction between Leucine-rich Repeat Kinase 2 and Specific β-Tubulin Isoforms Regulates Tubulin Acetylation (2014-01-10)
Law, Bernard M. H.; Spain, Victoria A.; Leinster, Veronica H. L.; Chia, Ruth; Beilina, Alexandra; Cho, Hyun J.; Taymans, Jean-Marc; Urban, Mary K.; Sancho, Rosa M.; Blanca Ramírez, Marian; Biskup, Saskia; Baekelandt, Veerle; Cai, Huaibin; Cookson, Mark R.; Berwick, Daniel C. and Harvey, Kirsten
Journal of Biological Chemistry, 289(2) (pp. 895-908)

LRRK2: an éminence grise of Wnt-mediated neurogenesis? (2013)
Berwick, Daniel C. and Harvey, Kirsten
Frontiers in Cellular Neuroscience, 7, Article 82

LRRK2 functions as a Wnt signaling scaffold, bridging cytosolic proteins and membrane-localized LRP6 (2012-11-15)
Berwick, Daniel C. and Harvey, Kirsten
Human Molecular Genetics, 21(22) (pp. 4966-4979)

The importance of Wnt signalling for neurodegeneration in Parkinson's disease (2012-10)
Berwick, Daniel C. and Harvey, Kirsten
Biochemical Society Transactions, 40(5) (pp. 1123-1128)

LRRK2 signaling pathways: the key to unlocking neurodegeneration? (2011-05)
Berwick, Daniel C. and Harvey, Kirsten
Trends in Cell Biology, 21(5) (pp. 257-65)

A simple technique for the prediction of interacting proteins reveals a direct Brn-3a-androgen receptor interaction (2010-05-14)
Berwick, Daniel C.; Diss, James K. J.; Budhram-Mahadeo, Vishwanie S. and Latchman, David S.
The Journal of Biological Chemistry, 285(20) (pp. 15286-15295)

Regulation of Brn-3a N-terminal transcriptional activity by MEK1/2-ERK1/2 signalling in neural differentiation (2009-02-23)
Berwick, Daniel C.; Calissano, Mattia; Corness, Jacqueline D.; Cook, Simon J. and Latchman, David S.
Brain research, 1256 (pp. 8-18)

Role of protein kinase B in insulin-regulated glucose uptake. (2005-04-01)
Welsh, G. I.; Hers, I.; Berwick, D. C.; Dell, G.; Wherlock, M.; Birkin, R.; Leney, S. and Tavaré, J. M.
Biochemical Society Transactions, 33(2) (pp. 346-349)

Protein kinase B phosphorylation of PIKfyve regulates the trafficking of GLUT4 vesicles (2004-12-01)
Berwick, Daniel C.; Dell, Ghislaine C.; Welsh, Gavin I.; Heesom, Kate J.; Hers, Ingeborg; Fletcher, Laura M.; Cooke, Frank T. and Tavaré, Jeremy M.
Journal of cell science, 117 (pp. 5985-5993)

Identifying protein kinase substrates: hunting for the organ-grinder's monkeys. (2004-05)
Berwick, Daniel C. and Tavaré, Jeremy M.
Trends in Biochemical Sciences, 29(5) (pp. 227-232)

The identification of ATP-citrate lyase as a protein kinase B (Akt) substrate in primary adipocytes. (2002-09-13)
Berwick, Daniel C.; Hers, Ingeborg; Heesom, Kate J.; Moule, S. Kelly and Tavare, Jeremy M.
Journal of Biological Chemistry, 277(37) (pp. 33895-33900)

PI3K, PTEN and Akt (2005)
Franke, Thomas F. and Berwick, Daniel C.
In: Dufour, Jean-Francois; Clavien, Pierre-Alain; Trautwein, Christian and Graf, Rolf eds. Signaling Pathways in Liver Diseases (pp. 239-257)
ISBN : 978-3-540-27194-9 | Publisher : Springer-Verlag | Published : Berlin, Heidelberg, New York

A comprehensive "Disease-in-a-Dish" approach to Parkinson's Disease (2017-04-10)
Azeggagh, Sonia; Adan, Abdullahi; Needs, Sarah; Murphy, Kerry; Allman, Sarah and Berwick, Daniel
In : British Neuroscience Association - 2017 Festival of Neuroscience (10-13 Apr 2017, Birmingham, United Kingdom)

CRISPR /Cas9 gene editing to study N-glycanase1 deficiency (2016-10-19)
Needs, Sarah; Adan, Abdullahi; Berwick, Daniel; Bootman, Martin and Allman, Sarah
In : 3rd BioProNET Annual Scientific Symposium (19-20 Oct 2016, East Midlands Conference Centre, Nottingham, UK)