Focus Areas in the Genomic Medicine Cycle
Major leadership positions

Chair, MGH Committee on Fundamental Research

MGH Department/Division

Department of Neurology

MGH Unit(s)

Molecular Neurogenetics Unit


We use genomics approaches to study lysosomal disease.

The Cotman laboratory’s research is focused on understanding the role of the endosomal-lysosomal system in human disease, with a particular emphasis on NCL (Batten disease), the most common cause of neurodegeneration in childhood that also more rarely affects adults. The main approaches undertaken are 1) to identify genetic variants leading to Mendelian lysosomal disease, 2) to develop genetically accurate models and cell biological tools for interrogating the disease pathogenesis, and better understand the normal function of lysosomal disease-related genes, and 3) to identify disease modifiers (genetic and pharmacologic) to lay the groundwork for drug development.

Priority Projects

  1. Informed by human genetic data, we develop NCL disease models that are then used in research studies aimed at identifying the earliest consequences of NCL gene mutations at the molecular, cellular and whole organism levels. These models are also used in research aimed at identifying NCL protein function, which is important for rational treatment strategies for these devastating and fatal disorders.
  2. We are actively working with collaborators, both internally and from other institutions around the world, to conduct genetic studies to better define the molecular basis of the NCL disorders. Although the majority of NCL genes are now identified, enabling a molecular diagnosis in >90% of cases, some patients do not harbor mutations in the known NCL genes, and interpretation of genetic data even in known genes remains a challenge. We are also using our genetic model systems to screen for and test candidate disease modifiers in preclinical studies using our genetic disease models.
  3. The most recent genetic advances in the field have highlighted an increasingly complex genetic and clinicopathologic picture of the NCL disorders and one that shows significant overlap with other neurodegenerative diseases. We are interested in better understanding these complex genotype-phenotype relationships and the pathway crosstalk across neurodegenerative diseases, and we are using our disease models and other genetic tools to accomplish this.
  4. With academic and industry partners, we are carrying out preclinical analysis of candidate therapeutics that have been identified through our basic research on NCL disease mechanisms.

Lab Members

Uma Chandrachud, Ph.D.UCHANDRACHUD [@] mgh.harvard.eduResearch Scientist
Luca MontoreLMONTORE [@] mgh.harvard.eduResearch Technician
Seda Yasa, Ph.D.SYASAERCAN [@] mgh.harvard.eduPostdoctoral Research Fellow
Brigitte DemeloBDEMELO [@] mgh.harvard.eduResearch Technician
Lab/Contact Telephone


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