Research Overview —
Our lab is focused on discovering the underlying mechanism of Alzheimer’s disease in relation to the chemistry and biology of γ-secretase. Mutations in the catalytic component of γ-secretase, Presenilin, and mutations in the γ-secretase substrate Amyloid Precursor Protein (APP) lead to Familial Alzheimer’s disease. My project uses the genetic animal model Caenorhabditis elegans to investigate the effects of these mutations on the worm physiology. Previous work in our lab has shown that mutations in Presenilin lead to age-dependent synaptic degeneration and reduced lifespan, a phenooytpe is that is amyloid-beta independent. My aim is to further investigate mutations to determine their phenotype, and to investigate whether this phenotype is due to a loss or gain of function of the enzyme.
Publications —
Devkota, S., Zhou, R., Nagarajan, V., Maesako, M., Do, H., Noorani, A., Overmeyer, C., Bhattarai, S., Douglas, J.T., Saraf, A., Miao, Y., Ackley, B.D., Shi, Y., Wolfe, M.S. (2024). Familial Alzheimer mutations stabilize synaptotoxic γ-secretase-substrate complexes. Cell Reports, 43(2):113761: pp. 1-39. https://doi.org/10.1016/j.celrep.2024.113761
Overmeyer, C., Jorgensen, K., & Vohra, B.P.S. (2023). The Translocase of the Outer Mitochondrial Membrane (TOM40) is required for mitochondrial dynamics and neuronal integrity in Dorsal Root Ganglion Neurons. Molecular and Cellular Neuroscience, 125 (103853): pp. 1-15. https://doi.org/10.1016/j.mcn.2023.103853
Presentations —
Poster Presentations
Chemical Biology Symposium, The University of Kansas, Synaptic degeneration and reduced lifespan in Familial Alzheimer’s Disease C. elegans Model Not Due to Simple Loss of Function of γ-secretase, October 2024
Annual Meeting, Missouri Academy of Science, Investigating the Effect of TOM40 on Mitochondrial Function in Neurodegenerative Pathologies, April 2019
Duke Colloquium, William Jewell College, How Tributyltin toxin affects the determination and differentiation of stem cells, and what it means for human embryos, April 2019
Oral Presentations
Duke Colloquium, William Jewell College, Investigating the Effect of TOM40 on Mitochondrial Function in Neurodegenerative Pathologies, April 2021