Research Interests

I maintain a long-standing interest in understanding the link between how brain energy use changes with age and neurodegenerative disease. Since joining HEB in July 2020 I have become interested in figuring out how and why human sleep patterns evolved and whether this pattern of high-REM, short total sleep duration has left us more susceptible to neurodegenerative disease. Ongoing projects are listed below. 

Human sleep patterns

Human sleep appears to be of relatively short duration when compared to that of our closest extant primate relatives (chimps and bonobos), additionally we humans spend a greater proportion of our time asleep in REM sleep. I'm interested in figuring out whether this is a consequence of our neuroarchitecture, or whether these sleep patterns were established early in the human lineage and helped to shape our neuroarchitecture. As the sleep patterns of our closest primate relatives remain unstudied, I look to genetic markers associated with short and long sleep duration to determine how human sleep patterns evolved. 

Brainstem tau progression and sleep loss

In collaboration with Dr. Patrick Fuller (UC Davis). 

Late-Stage AD is characterized by profound neuronal loss and the presence of intracellular neurofibriallary tangles containing of tau (membrane-associated protein tau; MAPT) and extracellular plaques containing beta amyloid (Ab). Neuropathological investigation of early-stage and prodromal AD brains reveals that tau deposition in the brainstem is an early pathological event while tau inclusions appear later. It is also interesting to note that tau pathology ascends to the cortex from the brainstem while Ab pathology descends from the cortex. As sleep loss in midlife is associated with a higher risk for AD we investigate whether this is associated with tau deposition in brainstem areas involved in regulating sleep along with the cellular consequences of tau and Ab deposition. 

Metabolomics of NAD+ metabolism and mitochondrial dysfunction

Dietary supplementation with the NAD+ precursors nicotinamide riboside (NR) or nicotinamide mononucleotide (NMN) is thought to improve health during aging and many people take these bioactive nucletides orally with the hope of extending lifespan. In this work, I treated mtDNA mutator mice with a regimen of NMN supplementation that was previously associated with beneficial effects in middle-aged mice. Here, I found that supplementation with NMN increased the risk of early death in mtDNA mutator mice and conduced a metabolomic study to determine the biochemical pathways affected by NMN supplementation in the context of dysfunctional mitochondria.