Zhiyuan Shen
Rutgers University-New Brunswick, NJ·Biochemistry
Cells constantly repair broken DNA and rescue stalled DNA copying (replication) to keep their genetic code accurate. When repair fails, chromosomes become unstable, which can lead to cancer.
- Fields
Biochemistry
Genetics
Biology
- Topics
DNA repair
genome instability
BRCAness
- Grants
- 3 known grants, through Jun 2027
What they work on
- Reveal how chromatin context, shaped by methylation, sumoylation and ubiquitination tags, controls the recruitment and function of the BRCA1-PALB2-BRCA2 repair complex and regulators such as 53BP1, RNF4 and BARD1.
- Define the roles of the BRCA network in DNA replication and tumor suppression, and map the genomic consequences of BRCA dysfunction.
- Explore new therapeutic opportunities that exploit BRCA network defects (BRCAness) in medulloblastoma and breast cancer.
- Determine how methylation of Ku70 by SETD4 affects Ku70/Ku80 stability, DNA binding, repair of double-strand breaks and radiation sensitivity, and its anti-apoptotic role in the cytoplasm, using custom antibodies and knock-in mice.
- Identify the parts of the SETD4 enzyme needed to methylate Ku70 and test whether SETD4 activity releases Ku70 from DNA damage sites, using a tagged Setd4 mouse line to study development and tumorigenesis.
- Test whether losing one copy of Bccip makes blood stem and progenitor cells more vulnerable to radiation, weakens bone marrow rebuilding, or impairs the bone marrow niche, using short- and long-term mouse experiments.
- Map tumor clonality and chromosome rearrangements in radiation-induced tumors of normal and Bccip-deficient mice with genomic and computational tools, and define how PARP1-driven PARylation recruits BCCIP to DNA damage sites.
More about the research
Faulty repair can also leave tumors vulnerable to drugs that exploit the defect. The lab's projects study the proteins that guard the genome: how they are controlled, how their loss promotes cancer, and how this knowledge can guide treatment. The work spans a multi-team program on the BRCA protein network, a study of how a chemical tag redirects the repair protein Ku70, and a study of how the gene Bccip protects blood-forming cells from radiation.
Why it matters
Tumors with BRCA-type repair defects make up as many as 12% of human cancers. Understanding these defects could point to better targeted treatment for such tumors, including breast cancer and medulloblastoma. Work on Ku70 and SETD4 could clarify why cells damaged by radiation live or die, which shapes both tumor development and treatment outcomes. The Bccip studies could help identify ways to protect or restore bone marrow after radiation exposure.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Dale A Ramsden
University of North Carolina at Chapel Hill, NC·Biochemistry
Determine how Pol θ's interactions with the DNA-copying machinery, including the polymerase Pol δ and the DNA clamp PCNA, affect cells' need for Pol θ-mediated end joining.
Sandeep Burma
University of Texas Health Science Center at San Antonio, TX·Biochemistry
Determine the biological role of the newly found ability of 53BP1, a chromatin-reading DNA repair protein, to bind double-stranded DNA, and how this binding recruits partner proteins and sets which repair pathway a break uses.
Joshua Heyza
Wayne State University, MI·Biochemistry·Early-career
Determine what the intrinsically disordered PST repeat domain of MDC1 binds on chromatin and how phosphorylation regulates that tether, using molecular, biochemical and biophysical approaches together with live-cell single-molecule imaging.
The school
Rutgers University-New Brunswick: 57 labs on PI Pages, $837M a year on research, 713 research doctorates a year.
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