David Pearce, Ph.D.
Associate Professor of Biochemistry & Biophysics, Neurology
Ph.D. 1990, University of Bath, England

Research: Use of yeast and mouse models for the study of children’s neurodegenerative disease.

The Pearce lab has a general interest in genetically inherited diseases of children. More specifically our goal is to contribute to the understanding of the molecular basis of several pediatric neurodegenerative diseases. The disease that is our primary focus is Batten disease. Batten disease is a type of Neuronal Ceroid Lipofuscinosis, so called because of the fact that a part of the cell called the lysosome accumulates a heterogeneous mix of fat-like material called lipofuscin. Many other diseases that result in brain degenerative diseases in children result from accumulation of other biological compounds in the lysosome. These are collectively termed Lysosomal Storage Disorders. Through exploration of our website you will find that we are interested in these other Lysosomal Storage Disorders also, but resources and ideas currently limit us to focus most of our efforts on Batten disease.

Batten disease results from the inheritance of two mutated copies of the human CLN3 gene. The effects of this are devastating. Children with Batten disease slowly lose their vision from around the age of 5-7 years of age. Following this, cognitive abilities decline slowly and seizures are common. Generally as a result of a slow decline, Batten disease is fatal. To understand why mutations and therefore altered function of CLN3 result in Batten disease, we need to first understand the function of CLN3 in normal cells. A lot of this research is done using yeast cells that contain a gene called BTN1 that is essentially the same as CLN3 in humans. A second focus of our research is the characterization mouse models for Batten disease. This approach utilizes a mouse that has been constructed to lack the CLN3 gene, enabling us to follow and pin-point changes that result in a mouse that has a defect similar to that in the disease. Ultimately the aim of any research on a genetic disorder is to devise interventions that may compensate for the defect.

Pearce Lab Website