Sabrina Spencer
University of Colorado Boulder, CO·Biochemistry
Cell division is usually drawn as a fixed assembly line, but cells appear to be far more flexible than that picture allows. They can take alternative routes to divide, and they can stop dividing in ways that range from a temporary pause to a permanent exit.
- Fields
Biochemistry
Biology
Genetics
- Topics
cell cycle
cyclin-dependent kinase inhibitors
Rb phosphorylation
- Grants
- 2 known grants, through Aug 2028
What they work on
- Test whether p16, a protein that naturally blocks the kinases CDK4 and CDK6, controls the rebound of CDK2 activity seen in single cells hours after CDK2 inhibition, using time-lapse microscopy of living cells.
- Determine whether CDK2-dependent degradation of Cyclin D, the activating partner of CDK4/6, tunes the rebound in CDK2 substrate phosphorylation during drug treatment.
- Identify additional mechanisms that keep phosphorylation of the brake protein Rb robust when CDK2 is inhibited, and show how long-term drug pressure exposes the interchangeability of CDKs.
- Evaluate how well prevailing senescence markers work as yes/no indicators of senescence versus graded readouts of quiescence depth, using fluorescent cell-cycle sensors and automated single-cell tracking.
- Compare quiescent and senescent cells transcriptome-wide to test whether they are separate states or points on a continuum of cell-cycle withdrawal.
- Pinpoint the DNA damage and telomere features that predict permanent cell-cycle exit as cells divide toward replicative senescence, by following individual cells over long time courses.
More about the research
Both behaviors matter medically: flexibility lets tumor cells resume growth despite drugs designed to stop them, while permanent exit, called senescence, is desirable during cancer therapy yet contributes to the decline of tissues with age. Work here uses long-term time-lapse microscopy of individual living cells, automated single-cell tracking, and fluorescent sensors that report on cell-cycle activity, tools that reveal cell-to-cell differences invisible in bulk measurements of whole populations.
Why it matters
Cells that reroute around cyclin-dependent kinase inhibitors are a route to drug resistance, so mapping those bypass mechanisms could help make targeted cell-cycle drugs work longer in cancer patients. Defining senescence molecularly could improve predictions of tumor relapse after therapy, give a way to gauge a cell's physiological age and remaining divisions, and make senolytic drugs that clear senescent cells safer to use.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Davis Englund
University of Alabama at Birmingham, AL·Physiology·Early-career
Define the core features of muscle fiber senescence by overexpressing p21, a cell-cycle-halting protein, in muscle fibers of living mice and combining validated senescence markers with transcriptome-wide analysis to find candidate therapeutic targets.
David Morgan
University of California-San Francisco, CA·Biochemistry
Determine how cyclin-dependent kinases (Cdks), enzymes that tag proteins with phosphates, build complex multisite phosphorylation patterns on their substrates in the eukaryotic cell cycle, using biochemical approaches.
Herman Sintim
University of Notre Dame, IN·Chemistry
Biochemically characterize second-generation 3H-pyrazolo[4,3-f]quinoline kinase inhibitors and use new chemistry to make third-generation compounds with better drug-like properties that target FLT3, CDK2, CDK12/13 or CDK18.
The school
University of Colorado Boulder: 36 labs on PI Pages, $718M a year on research, 447 research doctorates a year.
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