Gregory Petsko
Columbia University, NY·Biochemistry
Alzheimer's disease has no preventive or significantly disease-modifying treatment, and only four genes are known to truly cause it. One of them, SORL1, carries variants linked to about 3% of all cases, and some versions cause late-onset disease that looks like the common form.
- Fields
Biochemistry
Biophysics
Neuroscience
- Topics
Alzheimer's disease
retromer
endosomal trafficking
- Grants
- 1 known grant, through May 2030
What they work on
- Measure how disease-linked SORL1 mutations affect pairing of SORL1 proteins, binding to the retromer sorting complex and binding to APP, the amyloid precursor protein, using biochemical assays.
- Determine how SORL1 variants change the protein's folding, stability and motion using biophysical measurements.
- Solve crystal structures of selected mutant SORL1 proteins in the VPS10 region to reveal atomic-level changes in the local and overall shape of these domains.
- Use an AlphaFold3 model of the SORL1 outer region to guide cryo-electron microscopy structure determination and predict how other mutations alter SORL1 shape and function.
More about the research
More than 500 SORL1 variants are known, so doctors need to know which ones actually cause disease. This project, part of a larger multi-project program on SORL1, asks how disease-linked mutations change the shape and behavior of the SORL1 protein.
Why it matters
Knowing how a SORL1 mutation changes the protein could help doctors tell whether a patient's variant causes Alzheimer's disease. It could also show whether that patient might benefit from therapies designed to restore protein traffic out of endosomes, a possible treatment approach for a disease that currently lacks disease-modifying drugs.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Dibyadeep Datta
Yale University, CT·Neuroscience
Define the spatial relationship between pT217Tau, an early blood and spinal fluid marker of Alzheimer's, endosome enlargement and APP/Aβ42 in postmortem human brains across Braak stages, using quantitative immunofluorescence in vulnerable and resistant cortical regions.
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.
Maciej Stawikowski
Florida Atlantic University, FL·Chemistry
Design and synthesize environment-sensitive fluorescent cholesterol probes (CNDs) built on a 1,8-naphthalimide dye, using computational chemistry to tune their properties for different imaging uses.
The school
Columbia University: 89 labs on PI Pages, $1.4B a year on research, 625 research doctorates a year.
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