Focus Areas in the Genomic Medicine Cycle

MGH Department/Division

Movement Disorders

MGH Unit(s)

Molecular Neurogenetics Unit


Neurodegenerative diseases caused by microsatellite repeat expansions.

Repeat expansion diseases such as Huntington’s disease (HD) are characterized by the instability of their causative repeat mutations. The inherited repeat undergoes further somatic expansion that drives disease pathogenesis. Our lab uses patients and model systems to characterize and uncover the underlying modifiers and mechanisms of repeat instability in order to identify targets for disease-modifying therapies. We have identified several DNA repair genes as key players in this process. The main focus of the lab is HD, but we are very interested in understanding shared mechanisms with other repeat expansion diseases, in particular spinocerebellar ataxias, X-linked dystonia parkinsonism (XDP) and C9orf72 amyotrophic lateral sclerosis/frontotemporal dementia.

Priority Projects

  1. Novel Huntington’s disease modifiers. We use CRISPR-based tools and genetic strategies in HD mouse models to identify novel modifiers of HD CAG repeat instability and their impact on downstream phenotypes.
  2. Functional dissection of human Huntington’s disease modifier genes. Starting with human genetic variants that modify HD we conduct molecular, cellular and biochemical studies to understand their functional impacts.
  3. The role of somatic repeat instability in X-linked dystonia parkinsonism (XDP). XDP is associated with a hexanucleotide repeat tract. We are investigating the instability of this repeat and its role in disease.
  4. Cell-type dissection of repeat instability. We are performing studies aimed at understanding the dynamics of repeat instability at the level of individual cell-types and cells.

Lab Members

Alan Mejia Mazaamejiamaza [@] mgh.harvard.eduPostdoctoral Research Fellow
Marion (Joe) Riggsmriggs [@] mgh.harvard.eduPostdoctoral Research Fellow
Solaleh Tusiskhoramiantusi [@] mgh.harvard.eduPostdoctoral Research Fellow
Jea-Hwang Leejlee252 [@] mgh.harvard.eduResearch Scientist
Marina Kovalenkomkovalenko [@] mgh.harvard.eduSenior Research Technologist
Zoe Burchzburch [@] mgh.harvard.eduResearch Technologist (pending)
William Stifflerwstiffler [@] mgh.harvard.eduResearch Technician
Jessica Ulloajulloa1 [@] partners.orgResearch Technician
Lab/Contact Telephone




Primary Email

Wheeler [@]