Principal Investigator David Housman
The current research goals include identifying modifier genes which are responsible for variation in age of onset for HD. Prospective studies on extended HD families demonstrate that, other than the length of the CAG repeat sequence, modifier genes contribute significantly to determining the age of onset for HD. We are currently pursuing genetic linkage and association studies designed to identify these genes. In parallel, we are carrying out studies to identify genes which contribute to the timing of disease onset in mouse model systems for HD. We have also developed a series of model systems for the pathological effects of expanded polyglutamine repeats in Huntington's disease. Using these systems we have achieved the following goals:
(1) Developed genetic suppressors of the pathological effects of expanded polyglutamines and assessed the mode of action of these suppressors.(2) Isolated small molecules which inhibit the pathological effects of expanded polyglutamines.(3) Identified a pathway to pathology which involves transcriptional disregulation and the inhibition of histone deacetylase activities.
Current goals are focused on the identification and development of small molecules which show promise for therapeutic intervention in HD.