Chimeric antigen receptor (CAR) natural killer (NK) cells represent a promising experimental cell therapy, but the molecular mechanism regulating their activity is not fully understood. In a new study, researchers led by Katy Rezvani, M.D., Ph.D., and Hind Rafei, M.D., identified a protein – cAMP response element modulator (CREM) – as a critical checkpoint regulator of CAR NK cells that, when upregulated, limits the effectiveness of CAR NK cells. Researchers used CRISPR gene editing to target and knock...

High-risk multiple myeloma is an aggressive disease in which plasma cells grow uncontrollably. It is typically resistant to treatment and the prognosis for patients is poor. However, the genes that contribute to this behavior are not fully understood. Using single-cell transcriptomics, researchers led by Robert Orlowski, M.D., Ph.D., identified that CLPP, a protein in mitochondria, is overexpressed in high-risk cases and may also enable progression from earlier precursor cases to more advanced disease. Inhibiting CLPP genetically or through treatment...

BRCA2, a key tumor suppressor that helps repair and protect DNA during replication, is often mutated in cancer cells. Normally, BRCA2 interacts with another protein, RAD51, to suppress genomic instability by fixing damage at DNA breaks or by protecting DNA at stalled replication forks, which can occur during DNA replication. By examining the protein structure of a specific region of BRCA2, known as the C-terminal end, researchers led by Katharina Schlacher, Ph.D., and John Tainer, Ph.D., uncovered a...