PIPages
Labs

Shaun Olsen

University of Texas Health Science Center at San Antonio, TX·Biochemistry

Cells constantly repair their DNA and destroy proteins on schedule, and failures in either process can lead to cancer. Both projects use structural biology to see, at the level of molecules, how protein machines do these jobs.

Fields

Biochemistry

Biophysics

Biology

Topics

DNA repair

homologous recombination

double-strand break repair

Grants
2 known grants, through Apr 2029

What they work on

  1. Determine the structural and molecular basis by which the RAD51 paralog complex CX3 (RAD51C-XRCC3) promotes RAD51 filament assembly on single-stranded DNA, using cryo-EM and biochemical assays.
  2. Determine how the BCDX2 complex mediates RAD51 filament assembly and how cancer-linked defects disrupt it, combining cryo-EM, single-molecule DNA curtain assays and cell-based studies.
  3. Examine how higher-order assemblies of CX3 and BCDX2 with PALB2 and HELQ swap RPA for RAD51, confer resistance to DNA-damaging agents and protect stalled replication forks.
  4. Determine the structural basis by which Cdc34 and SCF E3 ligases specifically assemble lysine 48-linked ubiquitin chains to control the cell cycle, using structural, biochemical and cell-based approaches.
  5. Define the molecular mechanisms by which PROTAC molecules hijack cullin-RING E3 ligases to ubiquitinate target proteins and send them to the proteasome.

More about the research

One studies proteins that help mend broken DNA. The other studies enzymes that tag proteins for destruction. The goal is to understand these machines well enough to guide new cancer drugs.

Why it matters

Faulty DNA repair and runaway cell division drive cancer. Revealing how RAD51 paralog complexes repair broken DNA could provide a basis for small-molecule drugs aimed at breast, ovarian and other cancers. It could also clarify how inherited mutations raise cancer risk. Learning the rules by which PROTACs hijack E3 ligases could guide the design of more effective protein-degrading drugs for cancer and other diseases.

Known grants

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

Structure and function of RAD51 paralog tumor suppressor complexes in genome maintenance

NIH · May 2024 – Apr 2029

Structure and Function of the Essential Cell Cycle Regulator Cdc34

NIH · Apr 2019 – Feb 2027

Closest labs

Stephanie Gates

University of Missouri-Columbia, MO·Biochemistry

Dissect how the Hsp70/CHIP/BAG-1 chaperone complex affects each step of proteasomal degradation, including ubiquitin tagging, substrate binding and breakdown, using in vitro assays with purified proteins.

Michael James Emanuele

University of North Carolina at Chapel Hill, NC·Biochemistry

Define the wave of protein destruction occurring in G2 and at the G2-to-mitosis transition, determining which proteins are degraded and when, and how the phosphate-adding enzyme PLK1 controls this program, using proteomics and cell-based assays.

Jaewon Chang

Emory University, GA·Chemistry

Design and synthesize covalent warheads that react with lysine, tyrosine and serine residues on E3 ubiquitin ligases, the enzymes that tag proteins for destruction, going beyond the cysteine-reactive chemistry used so far.

The school

University of Texas Health Science Center at San Antonio: 15 labs on PI Pages, $313M a year on research, 149 research doctorates a year.

More about University of Texas Health Science Center at San Antonio

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