David Shechner
University of Washington, WA·Biochemistry
The cell nucleus is not a uniform bag of DNA. It contains dozens of distinct compartments that have no surrounding membrane yet still concentrate specific proteins, RNAs and stretches of the genome in one place.
- Fields
Biochemistry
Genetics
Biology
- Topics
nuclear bodies
Cajal body
nucleolus
- Grants
- 1 known grant, through Apr 2028
What they work on
- Generate a high-confidence catalog of the proteins, transcripts and genomic loci that make up Cajal bodies, using O-MAP, an RNA-targeted proximity-biotinylation method that tags molecules near a chosen RNA inside intact cells.
- Determine how Cajal body components are spatially arranged using structured illumination super-resolution microscopy, which resolves features finer than conventional light microscopy can.
- Compare Cajal body molecular architecture across a panel of cell types and cancer cells to test whether this compartment's composition is adapted to different cellular states and disease contexts.
- Reconstruct the order of events in Cajal body biogenesis by triggering assembly with a drug-inducible system and applying O-MAP and super-resolution imaging at successive time points during assembly.
More about the research
These nuclear bodies organize fundamental jobs: building ribosomes, cutting and splicing messenger RNA, repairing damaged DNA. Many of them are assembled from scratch in minutes when the cell needs them, gathering hundreds of components around RNA molecules that act as scaffolds. When this compartment architecture goes wrong, the consequences show up across human disease, from neurodegeneration to cancer. The problem is that nuclear bodies have been almost invisible to standard tools: genome-mapping methods like Hi-C, which charts which DNA regions sit near each other, cannot see them, and they are too delicate and fast-changing to survive the grinding and purification steps of conventional biochemistry.
Why it matters
Loss of normal nuclear compartment organization is implicated in a range of human conditions, including neurodegenerative disorders and cancer, but the molecular makeup and assembly steps of most nuclear bodies have gone uncharacterized for decades for lack of suitable methods. A validated map of Cajal body composition and assembly, plus a reusable RNA-targeted proximity-labeling workflow, could give other researchers a practical way to study how these compartments change in disease states.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Warren Zipfel
Cornell University, NY·Biomedical Engineering
Design and build an automated dual confocal/two-photon microscope that can image a cell population, locate fluorescently labeled nuclear regions of interest, and irradiate them with femtosecond pulses at high throughput.
Ashwanth Christopher Francis
Florida State University, FL·Microbiology & Immunology
Determine whether phase separation by the mixed-charge RSLD region of CPSF6, a host RNA-processing protein, releases HIV-1 from nuclear pore complexes and recruits host proteins and nuclear speckle components needed for viral transport.
Guillaume Chanfreau
University of California-Los Angeles, CA·Biochemistry
Determine how nuclear ribonucleases, including the RNA exosome, RNase III and the Rex exonucleases, regulate expression of chromatin remodeling factors such as bromodomain proteins when cells are placed under stress.
The school
University of Washington: 81 labs on PI Pages, $1.7B a year on research, 694 research doctorates a year.
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