Expanded repeat disorders: from mechanisms to therapies

Exploring the latest biology of repeat loci in the genome and the diseases they cause

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Expanded repeat disorders: from mechanisms to therapies

The genome contains large numbers of repeated sequences and short tandem repeats alone make up 3% of the genome. These repeats tend to be unstable with a higher mutagenic rate than single-copy genomic regions. Repetitive sequences have downstream biological effects and there are now >50 diseases caused by expanded repeated tracts. Until recently sequencing such tracts has been challenging but this is now starting to change. This conference sets out to explore the latest research in repeat disease biology, examining the events that underlie repeat dynamics in the genome, their downstream effects and how they can manifest in disease. This increasing understanding of the underlying biology is leading to new therapeutic avenues being exploited to treat these diseases and we will hear about some of these advances. 

The main meeting will take place over two days, 15-16 June 2021. Each day will run for approx. 4.5 hours, 14:00-18:30 (BST).

An Early Career Researcher day will be held on 14 June 2021, 14:00 – 19:00 (BST). Presenters will be selected from abstracts and a full programme will be released in May.

Abstract submission

Abstract submissions are welcome for short talks and rapid fire talks. Speakers will be chosen to give either a short talk (10 min live) or rapid fire presentation (2 min pre-recorded video) during the event.

Deadline for abstract submission: Monday 3 May 2021

Abstract submission is now closed.

Schedule of Events
  • ECR Day - Monday 14 June

    – Please note all times are BST.


    2:00 – Welcome from the Co-Chairs (Emily Machiela, University of Central Florida & Celeste Suart, McMaster University)

    2:10 – Keynote: Toward understanding polyglutamine diseases: lessons learned as we move forward (Hank Paulson, University of Michigan)


    Session 1: Molecular Mechanisms driving Neurodegeneration

    Chairs: David Bushart and Hannah Shorrock

    3:00 – Oligodendrocyte maturation is impaired in early SCA3 disease pathogenesis (Kristen Schuster, University of Michigan)

    3:15 – The Effects of Expanded Ataxin-7 on Stress Granules (Frida Niss, Stockholm University)

    3:30 – Astrocyte metabolic activity is impaired in Huntington’s Disease (Jenny Lange, UK DRI at UCL)

    3:45 – Session 1 Rapid Fire Video Presentations
    ·       Marketta Kachemov, University of California Irvine
    ·       Ya Zhou, UK DRI at UCL
    ·       Franziska Hoschek, Ulm University
    ·       Maria Babu, Deutsches Zentrum für Neurodegenerative Erkrankungen
    ·       Maximilian Wagner, Ulm University

    4:00 – Break


    Session 2: DNA/RNA Targets for Polyglutamine Diseases

    Chairs: Charlene Smith-Geater and Carlos Barba Bazan

    4:15 – Somatic CAG expansion in Huntington’s disease is dependent on the MLH3 endonuclease domain, which can be excluded via splice redirection (Jennie Roy, Massachusetts General Hospital)

    4:30 – The effect of mismatch repair proteins in a Huntington’s disease cellular model (Joseph Stone, Cardiff University)

    4:45 – The Mechanism of Replication Stalling and Recovery within Repetitive DNA (Gideon Coster, Institute of Cancer Research)

    5:00 – Session 2 Rapid Fire Video Presentations
    ·       Joseph Hamilton, University College London
    ·       Amanda Sadan, University College London
    ·       Sandra Fienko, UK DRI at UCL

    5:15 – Break


    Session 3: Diagnostics, Biomarkers and Drug Discovery Initiatives

    Chairs: Lauren Byrne and Rachel Harding

    5:30 – Poly ADP-ribose binding by huntingtin and signal dysregulation in Huntington’s disease (Tamara Maiuri, McMaster University)

    5:45 – Identification of CTG.CAG contraction factors in Myotonic Dystrophy type 1 (Laure de Pontual, Sorbonne Université)

    6:00 –  Exercise acts via BDNF-TrkB signalling to rescue deficits in a mouse model of spinocerebellar ataxia type 6 (Anna Cook, McGill University)

    6:15 – Session 3 Rapid Fire Video Presentations
    ·       Lien Nguyen, University of Florida
    ·       Elsa Kuijper, Leiden University Medical Center
    ·       Nicole Zarate, University of Minnesota
    ·       Alshaimaa Abdelmoez, Ulm University
    ·       Amber Southwell, University of Central Florida

    6:30 – Closing Remarks (Emily Machiela, University of Central Florida & Celeste Suart, McMaster University)

  • Day 1 - Tuesday 15 June

    – Please note all times are BST.


    Session 1: Repeat analysis and dynamics

    Chairs: Lesley Jones and Christopher Pearson

    2:00 - Introduction to the conference (Lesley Jones, Cardiff University)

    2:05 - Short tandem repeat expansions in the 100,000 Genomes Project (Arianna Tucci, Queen Mary University of London)

    2:25 - Tandem repeat expansions in complex disorders: beyond the coding sequence (Ryan Yuen, University of Toronto)

    2:45 - Rapid Fire Video Presentations
    ·      
    Andreas Halman, University of Melbourne
    ·      Stephanie Tome, Sorbonne Université
    ·      Alysha Taylor, UK DRI at Cardiff

    2:55 - A short tandem repeat in TCERG1 drives association with onset of Huntington’s Disease (Sergey Lobanov, Cardiff University)

    3:05 - Identification of repeat expansion mutations using deactivated-Cas9-based repeat enrichment and detection (dCas9-READ) (Lien Nguyen, University of Florida)

    3:15 - Genome-wide patterns of de novo mutations at short tandem repeats (Melissa Gymrek, University of California)

    3:35 - Discussion (10 minutes)


    Session 2: DNA repair and somatic expansion

    Chairs: Ray Truant and Vanessa Wheeler

    3:55 – The dynamics of somatic expansion in DM1, HD and related CAG•CTG repeat disorders (Darren Monckton, University of Glasgow)

    4:15 - Innerworkings of the human DNA repair machine MutSbet (Lorena Beese, Duke University)

    4:35 - How polymerase behaviour sculpts the genomic distribution of short tandem repeats (Julian Sale, MRC Laboratory of Molecular Biology)

    4:55 - Huntingtin-lowering treatments that decrease huntingtin transcription reduce CAG-tract somatic instability? (Jeff Carroll, Western Washington University)

    5:15 - Ataxin-1 is signalled to DNA damage by ATM kinase (Celeste Suart, McMaster University)

    5:25 - Ribosome stalling in CAG expanded mHTT mRNA: a potential mechanism for HD pathogenesis (Srini Subramaniam, The Scripps Research Institute)

    5:35 - Somatic CAG expansion in Huntington‚Äôs disease is dependent on the MLH3 endonuclease domain, which can be excluded via splice redirection (Ricardo Mouro Pinto, Massachusetts General Hospital / Harvard Medical School)

    5:45 - Discussion (10 minutes)

    5:55-6:30 - Plenary: Title TBC (Don Cleveland, Ludwig Institute for Cancer Research)

  • Day 2 - Wednesday 16 June

    – Please note all times are BST.


    Session 1: Pathogenic Biology of Expanded Repeats

    Chairs: Erich Wanker and Diane Merry

    2:00 - Molecular and cellular effects of polyQ-expanded ATXN1 protein aggregation (Spyros Petrakis, Centre for Research and Technology Hellas)

    2:20 - Disease mechanism and therapeutic approaches for Kennedy's disease (Kurt Fischbeck, NIH)

    2:40 - The incomplete splicing of huntingtin (Gill Bates, UK DRI at UCL)

    3:00 - Rapid Fire Video Presentations
    ·      Patrick van der Wel, University of Groningen 
    ·      Taylor Brown, University of Minnesota 
    ·      Kristen Schuster, University of Michigan 
    ·      Frida Niss, Stockholm University 
    ·      Joseph Hamilton, University College London

    3:10 - Excitatory synapse loss and its in vivo functional correlation with 1H - MRS in the knock-in zQ175(Tg/0) mouse model of Huntington's Disease (Nicole Zarate, University of Minnesota)

    3:20 - Structural insights into the HTT-HAP40 complex and the effects of polyglutamine expansion (Rachel Harding, University of Toronto)

    3:30 - Loss of proteostasis in Huntington's disease-lessons from Cockayne syndrome (Maximillian Wagner, Ulm University)

    4:40 - Extracellular Vesicles in HD (Andreas Neueder, Ulm University)

    3:50 - Discussion (10 minutes)


    Session 2: Therapeutic Approaches in Repeat Diseases

    Chairs: Christopher Ross and Leslie Thompson

    4:05 - Targeting DNA damage repair pathways for trinucleotide repeat expansion diseases (Caroline Benn, LoQus23 Therapeutics)

    4:25 - Development of TTX-3360 to treat/prevent HD and other Repeat Expansion Disorders by Halting Somatic Expansion (Irina Antonijevic, Triplet Therapeutics)

    4:45 - From Spinal Muscular Atrophy to Huntington's Disease therapeutics (Rajeev Sivasankaran, Novartis)

    5:05 - A gene editing approach to contract CAG/CTG repeats (Vincent Dion, UK DRI at Cardiff)

    5:25 - Toward absolute huntingtin quantitation (Amber Southwell, University of Central Florida)

    5:35 - CK2 alpha prime and alpha-synuclein pathogenic functional interaction mediates inflammation and transcriptional dysregulation in Huntington’s disease (Rocio Gomez-Pastor, University of Minnesota)

    5:45 - Discussion (10 minutes)

    5:55-6:30 - Plenary: Meeting the Therapeutic Challenge of Huntington's disease (Sarah Tabrizi, UK DRI at UCL)

Meet the organisers

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Lesley JonesVanessa WheelerCeleste SuartEmily Machiela
UK DRI Associate Member
Professor of Neurogenetics  Cardiff University
Associate Professor
of Neurology Massachusetts General Hospital/ Harvard Medical School
PhD Candidate
Dr Ray Truant Lab McMaster University
Post-doctoral Fellow Southwell Lab University of Central Florida


If you have any questions or queries about the event, please get in touch with us at enquiries@ukdri.ac.uk

Banner image: Rost9/Shutterstock.com

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