Xinbin Chen
University of California-Davis, CA·Biochemistry
More than half of human cancers carry a broken copy of TP53, the gene for p53, a protein often called the "guardian of the genome" because it halts or kills cells with damaged DNA. Some tumors lose p53's protective function.
- Fields
Biochemistry
Pharmacology
Medicine & Clinical Research
- Topics
p53
tumor suppressor
triple-negative breast cancer
- Grants
- 3 known grants, through Feb 2030
What they work on
- Determine how CDK4/6 enzymes, the RNA-binding protein RBM38 and the protein-synthesis factor eIF4G together boost mutant p53 production, and whether CDK4/6 inhibitors suppress triple-negative breast cancers partly by lowering mutant p53.
- Test whether blocking the RBM38-eIF4G interaction, using the Rbm38-derived peptide Pep8SD or the small molecule 094-63, reduces mutant p53 levels and slows growth of mutant p53-expressing tumors.
- Test whether compound 094-63 prevents DNA damage from raising mutant p53 levels and makes mutant p53-expressing tumors more sensitive to DNA-damaging chemotherapy drugs.
- Determine what controls whether ferredoxin reductase (FDXR), a mitochondrial electron-transfer enzyme, moves into the nucleus, including the role of chemical modifications added to the protein after it is made.
- Determine how nuclear FDXR suppresses tumors by acting on p53 and its regulators Mdm2 and Mdm4, and how it shapes redox signals during DNA damage response and repair.
- Map the feedback loops linking the adhesion proteins NINJ1 and NINJ2 to p53, and test their roles in tumor suppression and NLRP3 inflammasome-driven pyroptosis, an inflammatory cell death, using cells and knockout mice.
- Test whether peptides Pep-1A and Pep-2A, which break apart the NINJ1-NINJ2 complex, can kill tumor cells that carry wild-type p53.
More about the research
Others make a mutant p53 that actively drives tumor growth, spread and drug resistance. The three projects here look for weak points in the p53 network from different angles: how to switch off harmful mutant p53, how a mitochondrial enzyme joins p53 in suppressing tumors, and how a pair of cell-surface proteins could be targeted to reactivate normal p53 in cancer cells.
Why it matters
Tumors driven by mutant p53, including triple-negative breast cancers, have few targeted treatment options. This work could yield candidate drugs, such as compound 094-63 and its analogs, that lower mutant p53 and may make chemotherapy work better. Separate projects could show whether the Ninjurin pathway is a drug target for cancers with normal p53, and explain how FDXR and p53 help cells respond to DNA damage and protect against tumors.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Dawn Chandler
Ohio State University, OH·Biochemistry
Identify the RNA sequences and the protein and RNA nuclear factors that regulate MDM2 alternative splicing to produce MDM2-ALT1, a p53-activating isoform, using splice regulation assays and gene editing.
Guillermina Lozano
University of Texas MD Anderson Cancer Center, TX·Genetics
Determine the roles of Eda2r, a cell-surface receptor that can trigger apoptosis, in p53-dependent cell outcomes and tumor suppression in mouse models.
Zahid Siddik
University of Texas MD Anderson Cancer Center, TX·Pharmacology
Test whether reducing MDM4, a natural inhibitor of the p53 tumor suppressor, restores basal p53 phosphorylation in cisplatin-resistant rare ovarian cancer subtype models, both in cultured cells and in animals.
The school
University of California-Davis: 49 labs on PI Pages, $1.0B a year on research, 647 research doctorates a year.
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