Susan L. Cotman, PhD
Sue received her Ph.D. from the Biochemistry Program at The Ohio State University, then pursued her postdoctoral training at Massachusetts General Hospital. Sue now leads a research laboratory focused on defining the role of the endosomal-lysosomal system in human disease, with a particular emphasis on Neuronal Ceroid Lipofuscinosis (NCL). Sue is the recipient of a Dubai-Harvard Foundation for Medical Research Collaborative Research Award and a Claflin Distinguished Scholar Award
Questions being addressed in the lab
- What are the molecular underpinnings of the Mendelian lysosomal disorders collectively referred to as Neuronal Ceroid Lipofuscinosis (NCL, also known as Batten disease)
- Can we leverage NCL genetic discoveries to better understand disease pathophysiology, improve diagnosis, and develop disease-modifying treatments
- Can understanding the molecular basis of NCL inform a better mechanistic understanding of related, more complex neurological disease
Projects underway to answer these questions
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.
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.
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.
Genetic disease models developed and used in the lab include lower organisms, knock-in mice, neuronal cell culture models, and human induced pluripotent stem (hiPSC) cells.
Genetic studies have identified new NCL-linked genes and candidate genetic modifiers of disease. Phenotypic screens in disease models have also identified target pathways for further drug development research.
Genotype-phenotype analysis is leading to improved understanding of common and distinct features of the NCLs and several late-onset neurodegenerative diseases. Identifying the common pathways across these diseases will advance a more thorough understanding of disease pathogenesis and could speed the development of therapeutics.