UCL

​UK DRI at UCL

"The UK DRI at UCL takes knowledge from the lab all the way to treatments for people living with dementia – drawing on biomarkers, imaging and clinical research facilities." Prof Karen Duff
UK DRI Associate Director (joining spring 2020)

1. At a glance

From lab bench to bedside, and back again 

UCL was selected as the hub of the UK DRI in 2016 because of its strength to bring together excellent clinical and basic neuroscience research to advance our understanding of neurodegeneration and identify novel targets and therapeutic approaches for dementia. As the hub, it has a larger research programme and also is the location for the national headquarters team who connect the whole institute together.

Research at the UK DRI at UCL covers the journey from the person living with dementia to the laboratory and back again - with improved diagnosis and potential therapies put to the test. The groups believe in intervening earlier in disease in order to change the trajectory.

We need to better understand the diversity and complexity of neurodegenerative diseases, like Alzheimer's disease, in order to understand the mechanisms involved, and ultimately how we can alter them to improve people's lives.

We must find treatments quicker, and that's why the UK DRI at UCL is taking a novel approach by integrating diverse expertise for efficiency, from genetics to diagnostics.

This work is enhanced by incredible clinical resources. Researchers have access to unique clinical cohorts, where comprehensive data has been collected throughout disease progression including memory assessments and brain tissue. The UK DRI at UCL provides a clinical arm to the whole of the UK DRI.

The future iconic home of the UK DRI at UCL will be alongside UCL's Queen Square Institute of Neurology in a new building on Gray's Inn Road.

Read more about the official opening of the UK DRI at UCL

Visit the UK DRI at UCL local website for up-to-date news.

2. Scientific goals

The mission of the UK DRI hub at UCL is to play a central and collaborative role in the UK DRI’s efforts to discover and deliver effective therapies. The mission involves forging effective cross-disciplinary teams and approaches to understand pathogenic mechanisms; developing innovative therapeutic approaches; and providing a translational arm to the UK DRI to harness clinical resources, test and deliver treatments to patients.

The team addresses the key unanswered mechanistic questions that link genetic and lifecourse factors to dysfunction in molecular pathways, in cells and in neural systems during the progression of dementia.

The hub brings these strengths in molecular and clinical resources together to enhance functional and mechanistic research into dementia. The ultimate goal is to identify novel drug targets and therapeutic approaches for a range of neurodegenerative diseases.

The strategic aims of UK DRI at UCL are:

  • to elucidate mechanisms of disease to understand the pathways from gene to clinical manifestation, in order to identify new therapeutic targets;
  • to take full advantage of UCL’s clinical strengths: its cohorts, biomarker capabilities, biological and pathological resources, its access to patients, clinical expertise and translational research facilities - to conduct research from bedside to bench and back;
  • to focus on preventing or slowing disease progression as early as possible - when the minimum of neuronal loss has occurred;
  • to build on (and link) expertise in genomics; in axonal transport and defects in membrane trafficking and signalling; in the molecular mechanisms of C9orf72; in Huntington’s disease; in Wnt signalling and synapse maintenance;
  • to build human research capacity in neurodegeneration through training and mentoring;
  • to be opportunistic and responsive to new technological and scientific advances.

Clinical resource

UCL has one of the strongest and broadest clinical dementia research programmes internationally. A major strength is its clinical cohorts, expertise and biological resources – these span the full spectrum of neurodegenerative disease with access to deeply and serially phenotyped disease cohorts, providing crucial research opportunities and material from blood and cerebrospinal fluid (CSF), brain and other tissue, fibroblasts and hiPSCs through to trial participants. This offers a translational arm to the UK DRI

Notable disease-based clinical and cohort strengths include (amongst others):

  • familial AD (the UK centre for fAD and UK representative in the international consortia of the Dominantly Inherited Alzheimer Network, DIAN, and the DIAN-Trials Unit);
  • sporadic, atypical AD (e.g posterior cortical atrophy; one of the largest and best studied PCA cohorts and led on international research criteria and genetics consortia)
  • FTD (internationally leading FTD centre; founder and lead of the Genetic FTD Initiative GENFI);
  • HD (exceptional cohort and trial strengths);
  • Birth cohorts – and in particular the 1946 birth cohort and the Insight46 substudy;
  • Therapeutic trial participants – a range of early (and late phase) studies (from AD to FTD to HD) are continuously underway offering the potential to access samples (and tissue) from patients who are being given novel therapies.

For some of these diseases, we have data that runs all the way from genetics and basic science, to models, biomarkers and cohorts first in human studies. In other areas (e.g AD) strong clinical research has not been as well matched in molecular, biochemical and cellular aspects – for AD this is now being addressed with Prof Bart De Strooper as a PI in addition to new fellows who bring expertise in biology of the condition. 

3. Collaborations

Within UK DRI

  • Prof Paul Matthews, UK DRI at Imperial
  • Dr Nathan Skene, UK DRI at Imperial
  • Prof Caleb Webber, UK DRI at Cardiff
  • Dr Gabriel Balmus, UK DRI at Cambridge
  • Prof Lesley Jones, UK DRI at Cardiff
  • Dr Emmanouil Metzakopian, UK DRI at Cambridge 

Beyond UK DRI

  • Drug development expertise, often limited within academia, is offered through Prof Paul Whiting and the Alzheimer’s Research UK UCL Drug Discovery Institute (DDI). The DDI has focused on small molecules, but with the recent £5million award from the Sigrid Rausing Trust (SRT) for a Genetic Therapies Programme at UCL, this will now be complemented by a number of gene-based therapeutic studies. The pre-clinical work will be complemented by funding to attract and facilitate clinical studies – following from, and building on, Prof Sarah Tabrizi’s antisense oligonucleotide (ASO) work. 
  • Genomics and genotype-endophenotype-phenotype relationships: (Prof John Hardy, together with other UCL researchers). John Hardy brings not only world-leading expertise and track record but also a world-wide set of collaborations – with projects currently underway on AD and PD involving China/Asia and Africa and with a consortium of companies that have conducted trials in AD.
  • Biomarkers: the UK DRI at UCL aims to be one of the leading dementia biomarker centres in the world. Building on investments from the Wolfson (LWENC), UCL cohort studies and the collaboration with Gothenburg, the UK DRI fluid biomarker lab (Prof Henrik Zetterberg) will develop and validate new biomarkers offering a national resource for biomarkers (within and beyond the UK DRI).
  • Pathological material from the Queen Square Brain Bank forms an invaluable resource to support basic mechanistic studies.  

4. Topics

Cell function, gene expression, biomarkers, microglia, clinical, axonal transport, Huntington’s, FTD, neural circuits, brain structure

5. Techniques

Single cell transcriptomic analysis, imaging techniques, biomarker analysis, hiPSC resources

6. Vacancies

Visit our Join Us page to see opportunities available at this centre.

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7. Meet the team

Adrian Isaacs3

Adrian Isaacs

  • UK DRI Group Leader
  • Frontotemporal dementia and amyotrophic lateral sclerosis disease mechanisms
  • UCL
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Uk Dri Our People Portrait Bart 1000 X700 White

Bart De Strooper

  • UK DRI Director
  • Investigating the cellular reaction to amyloid beta and Tau
  • UCL, Headquarters
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Carlo Sala Frigerio

Carlo Sala Frigerio

  • UK DRI Group Leader
  • Cellular and molecular mechanisms of dementia
  • UCL
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Frances Wiseman

Frances Wiseman

  • UK DRI Programme Leader for Animal Models & Group Leader
  • Mechanisms of Alzheimer's disease development in Down syndrome
  • UCL
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Giampietro Schiavo

Giampietro Schiavo

  • UK DRI Group Leader
  • Restoring axonal transport deficits as a therapeutic strategy for neurodegenerative diseases
  • UCL
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Gillian Bates

Gillian Bates

  • UK DRI Group Leader
  • The inter-relationship of somatic CAG instability, incomplete HTT splicing and huntingtin aggregation as pathogenic mechanisms underlying Huntington’s disease
  • UCL
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Henrik

Henrik Zetterberg

  • UK DRI Group Leader
  • Fluid biomarkers for neurodegenerative diseases
  • UCL
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John Hardy

John Hardy

  • UK DRI Group Leader
  • Analysis of neurodegeneration
  • UCL
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Karen Duff

Karen Duff

  • UK DRI Associate Director (Spring 2020)
  • Programme title: TBC
  • UCL
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Katharine Buckle

Katharine Buckle

  • Centre Manager, UK DRI at UCL
  • UCL
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Marc Aurel Busche

Marc Aurel Busche

  • UK DRI Group Leader
  • Understanding and repairing pathological neural circuits in Alzheimer's disease
  • UCL
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Nick Fox2

Nick Fox

  • UK DRI Group Leader
  • From Patient to Bench and Back: Clinical Resources, Accelerating Therapies
  • UCL
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Paul Whiting

Paul Whiting

  • UK DRI Group Leader
  • The role of Wnt signaling in neurodegenerative disease
  • UCL
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Sarah Tabrizi

Sarah Tabrizi

  • UK DRI Group Leader
  • Mechanism of the DNA damage response in Huntington's disease pathogenesis and relevance for therapeutics
  • UCL
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Soyon Hong

Soyon Hong

  • UK DRI Group Leader
  • Immune mechanisms of synaptic function and pathology
  • UCL
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Tim Bartels

Tim Bartels

  • UK DRI Group Leader
  • Structure-function relationship in neurodegeneration
  • UCL
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Founding funders

Latest tweets from @UKDRI

We're working across the spectrum of diseases that give rise to dementia 🧠 Explore our group leader profiles and f… https://t.co/5sgOxvh6u9
19 Nov 2019 17:55

RT @jojacksonhere: I wish I had this when I was characterising spine morphology...those long analysis days still haunt me! https://t.co/LJA
19 Nov 2019 17:43