A5018834609- Cancer-related gene regulation
- Epigenetics and DNA Methylation
- Protein Degradation and Inhibitors
- Cancer-related molecular mechanisms research
- RNA modifications and cancer
- RNA Research and Splicing
- Advanced Breast Cancer Therapies
The University of Texas Southwestern Medical Center
2022-2024
Howard Hughes Medical Institute
2023-2024
Southwestern Medical Center
2022-2024
Cellular senescence is an irreversible state of cell-cycle arrest induced by various stresses, including aberrant oncogene activation, telomere shortening, and DNA damage. Through a genome-wide screen, we discovered conserved small nucleolar RNA (snoRNA), SNORA13, that required for multiple forms in human cells mice. Although SNORA13 guides the pseudouridylation nucleotide ribosomal decoding center, loss this snoRNA minimally impacts translation. Instead, found negatively regulates ribosome...
Abstract CDK4/6 inhibitors (CDK4/6i) have improved survival of patients with estrogen receptor-positive (ER+) breast cancer. However, treated CDK4/6i eventually develop drug resistance and progress. RB1 loss-of-function alterations confer to CDK4/6i, but the optimal therapy for these is unclear. Through a genome-wide CRISPR screen, we identify protein arginine methyltransferase 5 (PRMT5) as molecular vulnerability in ER+/ -knockout cancer cells. Inhibition PRMT5 blocks G1-to-S transition...
CDK4/6 inhibitors (CDK4/6i) have improved survival of patients with estrogen receptor-positive (ER+) breast cancer. However, treated CDK4/6i eventually develop drug resistance and progress.
Abstract RB1 loss-of-function genomic alterations confer resistance to CDK4/6 inhibitors (CDK4/6i) and are enriched post treatment of CDK4/6i in estrogen receptor-positive (ER+) metastatic breast cancer. ER+/Rb-deficient cancer is a rising patient population need novel therapeutic strategies. Herein, we used genome-wide CRISPR screen identified protein arginine methyltransferase 5 (PRMT5) as molecular vulnerability this refractory subtype. sgRNA-induced depletion PRMT5 arrested growth MCF-7...
Abstract Background: CDK4/6 inhibitors (CDK4/6i) have improved survival of patients with advanced estrogen receptor-positive (ER+) breast cancer. However, this benefit is transient as virtually all these tumors eventually develop drug resistance and recur. Clinical studies reported an association RB1 loss-of-function genomic alterations acquired to CDK4/6i. Given the enrichment post CDK4/6i treatment, ER+/RB1-deficient cancer will become a rising patient population in need discovery novel...