Focuses on creating and characterizing mouse models that accurately model human disease and therefore can be used to understand neurodegenerative disease and be used in the development of new therapies.
As the Associate Director of Genetic Resource Science Model Development and Bioinformatics, I oversee the group responsible for the selection and importation of new mouse strains into the Repository. We curate strain information and develop tools that enable the public to access the information in our extensive strain database.
I also work on creating and characterizing mouse models that accurately model human disease and can be used in understanding neurodegenerative disease and in the development of new therapies. Ongoing projects are listed below.
Alzheimer's disease is the most common cause of dementia. It is characterized by brain pathology including amyloid plaques composed of Abeta and intracellular tangles made up of hyperphosphorylated tau protein. Abeta is a cleavage product of the amyloid precursor protein (APP), and mutations in APP and its processing enzymes (including the presenilins, Bace) are thought to be one cause of familial AD. The Jackson Laboratory offers a variety of genetic models for AD research, including strains expressing APP and presenilin (PSEN1) mutations, strains expressing mutant APP in either a constitutive or inducible manner, strains expressing mutant tau (Mapt), strains with Presenilin mutations, strains with Apoe mutations, and strains with Bace mutations. These models develop Alzheimer's-related characteristics as they age.
Parkinson's disease is characterized by the loss of dopamine-producing cells in the substantia nigra. While the earliest and most obvious symptoms are movement disorders including tremor, rigidity, gait abnormalities and bradykinesia (slowness of movement), there are many other manifestations, including cognitive, emotional and sleep disorders. Accumulation of alpha-synuclein deposits in the brain lead to the formation of Lewy bodies, a diagnostic marker of PD. The Michael J. Fox Foundation for Parkinson’s Research (MJFF) supports our program to develop, characterize, and distribute genetically engineered mice and information useful for their selection and use.
With funding from the Chordoma Foundation, we are developing and characterizing novels models of this rare form of skull and spine cancer.
With funding from the Dravet Syndrome Foundation, we have created a novel model of this form of early onset epilepsy. This model is currently being validated.