Molecular Pharmacology Lab

Leidos Biomedical Research, Inc., Frederick MD

Investigators

Abstract

This laboratory uses retinoic acid receptor (RAR, retinoid) and retinoid X receptor (RXR, rexinoid) agonists or antagonists and other agents as discovery tools to uncover critical antineoplastic pathways. The laboratory played a key role in identifying retinoid-based differentiation therapy as a successful (and FDA-approved) way to combat acute promyelocytic leukemia (APL), an early example of targeted cancer therapy. This team cloned the etiologic fusion protein, PML/RAR?, and developed the companion diagnostic genetic assay for Acute Promyelocytic Leukemia (APL). Currently, they are exploring the retinoid-regulated deubiquitinase USP18 and how retinoids cooperate in immune-based therapy. Recently, they discovered a pathway called anaphase catastrophe that can target aneuploid cancers (a hallmark of cancer) while sparing normal cells. Signals that trigger anaphase catastrophe are now under intensive study.