Ji Lab

Research Interests

Lipid transport between organelles — from mechanism to disease.

Cells constantly move lipids — phospholipids, phosphoinositides, ceramide, cholesterol, and fatty acids — from where they are made to where they are needed. Much of this traffic never uses vesicles. Instead, lipid transfer proteins (LTPs) extract individual lipids, or bridge them in bulk, directly across the narrow gaps between organelle membranes. We study how these molecular machines select, carry, and deliver their cargo to give each organelle its distinct lipid identity and metabolic function.

Our work centers on a newly appreciated class of bridge-like lipid transfer proteins (BLTPs) — the VPS13 family and SHIP164 — that form long hydrophobic channels for high-capacity lipid flow, together with SMP- and Sec14-domain transporters such as PDZD8, Tex2, and Sec14L6. Combining AlphaFold-guided structural modeling, in vitro reconstitution, lipidomics, and live-cell imaging, we define the adaptors that position each transporter and the cargo it moves — including lipid-handling roles, as for the large-mammal-specific Sec14L6, that are simply absent from yeast and fly models.

This matters for human health: VPS13B mutations cause Cohen syndrome, VPS13 and BLTP genes are tied to Parkinson's disease, spastic ataxia, and neurodegeneration, and faulty lipid delivery contributes to metabolic and developmental disorders. By following the path from a single gene mutation, to a defined lipid-transport defect, to disease, the lab works to turn the cell biology of lipid transport into a framework for understanding — and ultimately correcting — these conditions.

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