Research
We follow one thread end to end—structure → mechanism → variant effects → disease—using cryo-EM, computation, and biochemistry to turn molecular detail into an understanding of human health.
Research Themes
ABCA7 & Alzheimer’s Risk
We resolve the structure of the ABCA7 lipid transporter and study how it handles lipids at the membrane—tracing a path from genetic variation in ABCA7 to the cellular biology that shapes neurodegeneration and Alzheimer's disease risk. ABCA7 carries a stronger association with Alzheimer's disease risk in individuals of African ancestry than the APOE ε4 allele, and Dr. Davis and colleagues have reviewed how AD-associated ABCA7 mutations disrupt the transporter's structure and lipid-handling function and contribute to disease pathogenesis in Stepler et al., Journal of Alzheimer's Disease, 2022. That work anchors this lab's structural biology, genetics, and health-equity research program—see the group's full publication record for related studies. [expand with lab-specific structural findings]
Lipid Transport Mechanisms
We map the conformational cycles that move lipids across membranes—defining substrate paths through the transporter and the APOE-linked networks that regulate lipid homeostasis in the brain. ABCA7 dysfunction disrupts lipid handling, phagocytosis, and endoplasmic-reticulum homeostasis in ways linked to Alzheimer's pathology; Dr. Davis and colleagues review this mechanistic picture, and the AD-associated mutations that perturb it, in Stepler et al., Journal of Alzheimer's Disease, 2022. [expand with lab-specific mechanistic findings as they publish]
AI Structural Biology
We combine AlphaFold and Rosetta modeling with molecular dynamics simulations to interpret disease variants, dock ligands, and capture the conformational transitions that static structures miss—complementing the cryo-EM and biochemical work in Themes 01–02 with predictive models of how ABCA7 variants alter structure and function. [no dedicated publication or conference abstract on this computational work has been identified yet; findings will be linked here once published]
Methods
The experimental and computational toolkit behind every project.
Cryo-EM / Cryo-ET
Single-particle maps and cellular tomography for near-native transporter structures.
X-ray
Crystallographic structures for high-resolution detail and complementary states.
MD simulations
Molecular dynamics to probe transitions, energetics, and lipid interactions.
AI Structure Prediction
AlphaFold and Rosetta modeling to generate variant structures and inform where to focus experimental validation.