My laboratory is interested in understanding the molecular pathways that mediate the pathology of neurodegenerative disorders and cancer, with a focus on DNA repair processes in the central nervous system (CNS). Considering the aging population, and the fact that several neurodegenerative diseases preferentially afflict older individuals, an understanding of the mechanisms underlying age-dependent alteration of DNA repair capability, and the accumulation of DNA damage and/or mutations (as well as the pathological consequences thereof) is important to public health. Currently we focus on understanding the mechanism of expansion of simple repetitive sequences that cause over 50 human diseases, including Huntington’s disease, myotonic dystrophy type I, fragile X-related disorders. The work in our laboratory fit into three broad categories:
- Biochemical reconstitution of molecular pathways
- Cryo-EM visualization of molecular machines
- Cell biology of disease-associated neurons
Our overarching goal is to integrate these diverse approaches to develop a holistic understanding of the molecular pathways involved in repeat expansion.