Runx proteins and transcriptional mechanisms that govern memory CD8 T cell development.

Adaptive immunity to intracellular pathogens and tumors is mediated by antigen-experienced CD8 T cells. Individual naive CD8 T cells have the potential to differentiate into a diverse array of antigen-experienced subsets that exhibit distinct effector functions, life spans, anatomic positioning, and potential for regenerating an entirely new immune response during iterative pathogenic exposures. The developmental process by which activated naive cells undergo diversification involves regulation of chromatin structure and transcription but is not entirely understood.

Preparation of tetrasubstituted pyrimido[4,5-]pyrimidine diones.

A novel synthetic route to 1,3,5,7-tetrasubstituted pyrimido[4,5-d]pyrimidine-2,4-diones, of interest for potential antitumor activity, is reported. The route uses 1,3-disubstituted 6-amino uracils as starting materials. The key step is a hydrazine-induced cyclization reaction to form the fused pyrimidine ring.

Identification of small molecules that disrupt signaling between ABL and its positive regulator RIN1.

Constitutively active BCR-ABL kinase fusions are causative mutations in the pathogenesis of hematopoietic neoplasias including chronic myelogenous leukemia (CML). Although these fusions have been successfully targeted with kinase inhibitors, drug-resistance and relapse continue to limit long-term survival, highlighting the need for continued innovative drug discovery. We developed a time-resolved Förster resonance energy transfer (TR-FRET) -based assay to identify compounds that disrupt stimulation of the ABL kinase by blocking its ability to bind the positive regulator RIN1.