David Eisenberg
University of California-Los Angeles, CA·Biochemistry
Alzheimer's disease (AD) destroys memory and thinking in millions of people, and no drug halts the decline. Its brain damage is linked to proteins that clump together.
- Fields
Biochemistry
Biophysics
Pharmacology
- Topics
Alzheimer's disease
dementia
Tau
- Grants
- 1 known grant, through Jan 2027
What they work on
- Discover safe Tau disaggregants through repeated cycles of solving structures of Alzheimer's brain Tau fibrils bound to compounds and screening new compounds that fit the drug-binding site.
- Pair Tau disaggregants with brain-penetrant nanoparticles, working with a synthetic chemistry co-investigator, so the compounds can reach the brain.
- Determine atomic structures of toxic Tau and beta-amyloid oligomers by cryoEM, using a monoclonal antibody fragment (Fab) that extracts and stabilizes oligomers from Alzheimer's brains.
- Test whether drug candidates block the spread and damage of aggregated Tau in human brain organoids, lab-grown mini-brains, and compare results in a mouse model of tauopathy.
More about the research
One is Tau, whose clumping closely tracks the onset of dementia. Another is beta-amyloid. Drug design based on a target's atomic structure has worked against cancer and HIV. That strategy is now becoming possible for AD because new methods can reveal the atomic structures of these protein clumps. The main methods are cryo-electron microscopy (cryoEM), which images frozen molecules with electrons, and X-ray diffraction.
Why it matters
Alzheimer's disease affects about five and a half million Americans, and no drug stops their decline. Structures of toxic Tau and beta-amyloid aggregates could guide drugs that prevent, dissolve or block the spread of these aggregates. Human brain organoids could become a new way to test Alzheimer's drug candidates before human trials.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Kenneth Kosik
University of California-Santa Barbara, CA·Neuroscience
Determine the mechanism and build the tools to replicate tauopathy-specific tau fibrils in vitro, including Alzheimer's and corticobasal degeneration folds, so that PET imaging ligands, antibodies and small molecules can be screened against real disease structures.
Wei Qiang
Binghamton University, NY·Biophysics
Test proposed mechanistic models of local membrane leakage caused by on-pathway beta-amyloid fibril intermediates in liposomes, using solid-state NMR and signal-enhancing dynamic nuclear polarization.
James Solomon Fraser
University of California-San Francisco, CA·Biophysics
Improve computational methods for finding and modeling alternative protein shapes in cryoEM density maps, extending the multiconformer modeling the group built for X-ray crystallography.
The school
University of California-Los Angeles: 84 labs on PI Pages, $1.9B a year on research, 803 research doctorates a year.
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