The principal aim of my laboratory is to understand the molecular pathways that drive neuronal death in Huntington´s Disease (HD), an inherited neurodegenerative disorder caused by a CAG triplet repeat expansion within exon-1 of the Huntingtin gene (Htt). Mutant Htt protein aggregates and accumulates in virtually all cell types in the body, but it predominantly affects Medium Spiny Neurons (MSNs), a neuronal type located in the striatum. We focus on studies directed at understanding what makes MSNs so susceptible to mHtt aggregation and death compared to other cell types in the brain. We also examine the role of Heat Shock Factor (HSF1), a transcription factor that regulates protein folding, inflammation, and apoptosis, in a cell type-specific process. To address this question we apply molecular biology, biochemistry, neuroanatomy, and imaging to different HD cellular and mouse models as well as human specimens. Our final goal is to provide new therapeutic strategies to prevent neuronal death and improve the quality of life of thousands of patients with this devastating neurodegenerative disease.
