Ethan Lippmann

What they work on

1. Measure how dose affects gene and protein silencing by siRNA-EG18, an siRNA linked to an albumin-binding fatty acid carrier, in brain myeloid cells after injection into cerebrospinal fluid, targeting the Alzheimer's risk gene Cd33.
2. Test whether siRNA-EG18 still reaches myeloid cell subtypes in aged and amyloid-depositing mice, using single-cell sequencing to identify which cells are silenced under disease-like conditions.
3. Benchmark siRNA-EG18 against a lipid-siRNA conjugate already in phase 1 clinical testing for early-onset Alzheimer's disease, comparing distribution and knockdown in the brain.
4. Activate Wnt7 signaling specifically, via its receptors GPR124 and RECK, in naive iPSC-derived endothelial progenitors using CRISPR and synthetic biology, and test whether this gives more faithful blood-brain barrier identity than generic Wnt activation.
5. Extend engineered Wnt7 signaling into three-dimensional neurovascular assemblies to test whether barrier properties and endothelial character are retained in a multicellular setting.
6. Quantify three-dimensional spatial relationships between STAT3-activated astrocytes and sites of vascular damage in postmortem brain tissue from larger dementia cohorts using advanced imaging.
7. Inhibit STAT3 signaling in astrocytes of transgenic dementia mice and follow neurovascular changes over time, including single-cell RNA sequencing of endothelial cells along the whole vascular tree.
8. Test whether astrocyte-derived alpha 1-antichymotrypsin (ACT), a STAT3-controlled protease inhibitor, causes neurovascular dysfunction in dementia mice, and whether it acts synergistically with the risk gene APOE.
9. Grow cortical organoids in a biomaterial that mimics radial glia cues and characterize whether layered cortical architecture and maturation improve.
10. Integrate brain endothelial cells and pericytes into cortical organoids to create perfusable capillary-sized vessels, then challenge these neurovascular organoids with barrier-damaging injuries and compare iPSC lines of different APOE genotype.

More about the research

Why it matters

Brain vascular decline is a major modifier of Alzheimer's disease and a driver of vascular dementia and small vessel disease, for which treatments and models are scarce. Better human stem-cell models could let researchers test drugs and genetic risk factors such as APOE outside of animals. Identifying STAT3-driven astrocyte states may reveal targets for protecting brain vessels, and the albumin-binding siRNA carrier could offer a route to silence Alzheimer's risk genes in brain immune cells.

Known grants

From NIH and NSF research grants. Labs often have other funding we can't see.

Closest labs

The school

Vanderbilt University: 22 labs on PI Pages, $1.3B a year on research, 494 research doctorates a year.

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