Dawn Chandler
Ohio State University, OH·Biochemistry
The protein p53 guards the genome by stopping damaged cells from growing, and its function is disabled in more than half of human cancers. Besides mutations in p53 itself, cancers can switch it off by overproducing its inhibitors, MDM2 and MDM4.
- Fields
Biochemistry
Genetics
Medicine & Clinical Research
- Topics
MDM2-ALT1
p53
tumor suppressor
- Grants
- 1 known grant, through Aug 2027
What they work on
- 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.
- Test whether altered nuclear splicing factors during tumor progression drive the oncogenic expression of MDM2-ALT1 in cancers such as rhabdomyosarcoma and pediatric glioma.
- Use splice-switching oligonucleotides (SSOs), short strands that redirect RNA splicing, in genetically engineered mice and xenograft models to shift MDM2 isoform levels and control the p53 pathway.
More about the research
Cells can also make different versions of MDM2 through alternative splicing, in which pieces of a gene's RNA message are cut and joined in different ways. This project asks how one such version is produced in cancer and whether it can be redirected as a therapy.
Why it matters
Because MDM2 and its isoforms control p53, a key tumor suppressor, understanding how DNA damage and cancer shift MDM2 splicing could reveal new points for therapeutic intervention. Splice-switching oligonucleotides that adjust MDM2 isoforms may offer a route to controlling the p53 pathway in cancers such as pediatric gliomas and rhabdomyosarcoma.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Xinbin Chen
University of California-Davis, CA·Biochemistry
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.
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.
Jason Yustein
Emory University, GA·Medicine & Clinical Research
Map single-cell protein and RNA signatures and cell-cell communication in MYC-amplified human and mouse osteosarcoma, using patient-derived xenografts and engineered mice, and disrupt candidate metastasis-linked signals genetically.
The school
Ohio State University: 71 labs on PI Pages, $1.6B a year on research, 882 research doctorates a year.
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