The molecular mechanisms underlying neurodegenerative disease
Neurodegenerative diseases are fundamentally the result of aberrant proteostasis within neurons. My lab is interested in understanding the basic cell and molecular changes leading to this aberrant proteostasis in Alzheimer Disease, frontotemporal lobar degeneration and other neurodegenerative conditions. In particular, we are focused on the consequences of impaired autophagy and lysosomal function. The lysosome is not only the cell’s garbage can—rather, it is a central regulator of homeostasis, responsible for protein and lipid recycling, amino acid storage, appropriate stress response and regulated cell growth. We have shown that mutations responsible for neurodegenerative diseases can directly alter lysosome function with pleotropic downstream consequences. Our current work utilizes C. elegans, induced pluripotent stem cells (iPSC) and other cellular models to decipher how alterations in lysosome function, autophagy, cell and organelle pH and stress response programs can lead to neuronal dysfunction and death.
Current Projects
- Lysosomes, Aging and Neurodegenerative Disease
- Progranulin and Prosaposin in regulating lysosomal function
- Tau, TSC1 and mTOR activity
- New disease mechanisms for autosomal dominant mutations in alpha-synuclein, TDP-43 and Tau
- pH regulation and dysregulation in aging and disease
Academic community service and committee membership:
NS Diversity Co-Chair, NS Formal Seminar Committee, NS Curriculum Committee, NS Student Advisors/Student Progress, First-year advisor, Advise in BM and MSTP, hosted 3 SRTP students, MSTP Executive committee, Neurology Advancement and Promotions, have undergone extensive DEI training