Bradley Lab
Principal Investigator: Robert K Bradley
Institution: Fred Hutch Cancer Center (Seattle, WA)
Primary Subfield: Molecular & Cell Bio
Recruitment Status: Inquire for rotation/fellowship opportunities
Research Focus
SUMMARY Many cancers carry recurrent, change-of-function mutations affecting RNA splicing factors, resulting in sequence-specific changes in RNA splicing that promote disease initiation and progression. These “spliceosomal mutations” are the most common class of mutations in myelodysplastic syndromes (MDS) and related hematologic disorders, which have few effective, FDA-approved treatments. Despite the high frequency of spliceosomal mutations and corresponding need for new therapeutics, there currently exist no therapies that specifically and selectively target these lesions. Here, we propose to address this clinical need by creating new precision therapeutics that selectively kill cells with spliceosomal mutations. Our interdisciplinary team consists of a physician-scientist with expertise in cancer biology and patient care (Abdel-Wahab), a basic scientist with expertise in RNA splicing and functional genomics (Bradley), and a bioengineer with expertise in drug delivery (Heller). In preliminary experiments, we developed the “synthetic intron” technology to harness altered RNA splicing activity caused by spliceosomal mutations to drive cancer-specific gene expression, showed that s…
Active NIH Awards
- 5R01CA283364-04: Synthetic introns for selective targeting of RNA splicing factor-mutant leukemia (2026)
- 5R01HL128239-12: Genetic and molecular basis for SRSF2 mutations in myelodysplasia (2026)
- 2R01HL128239-11: Genetic and molecular basis for SRSF2 mutations in myelodysplasia (2025)
- 5R01CA283364-03: Synthetic introns for selective targeting of RNA splicing factor-mutant leukemia (2025)
- 5R01CA283364-02: Synthetic introns for selective targeting of RNA splicing factor-mutant leukemia (2024)
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