Jahan A. Rahman

In chronically stimulated human T cells, suppressed oxidative metabolism and nucleotide loss accompany MAP2K4 activation. Inhibiting MAP2K4 (with the MKK4/7 inhibitor BSJ-04-122) restored tumor-cell killing in vitro.

This study identifies somatic DDX41 mutations as gain-of-function alleles that drive aberrant splicing, particularly of SEPTIN7, contributing to MDS/AML pathogenesis.

This study shows that MEK inhibition reduces mitochondrial dysfunction and terminal CD8+ T cell exhaustion by decreasing nutrient uptake and RNA polymerase II activity.

This study identifies mRNA glycation by methylglyoxal as a metabolic stress sensor, showing impaired translation and beta-cell dysfunction, which is mitigated by metformin.

This study shows that limited amino acid availability in tumors impairs CD8+ T-cell cytotoxic function by reducing protein synthesis, and demonstrates strategies to restore this function.

This study develops chemical probes to target splicing factors in T cells, showing state-dependent loss of ITK via SF3B1 and demonstrating covalent ligandability of splicing regulators.

The paper predicts Cas13 guide RNA efficacy for transcripts in model organisms and viral RNA pathogens and provides a web tool for gRNA design.

The paper develops an automated pipeline to design CRISPR prime editors for human pathogenic variants, finding that only a small fraction can be targeted but this number increases to over 50,000 with alternative Cas9 and templates.