Functional Genomic Screening to Identify Therapeutic Targets in Human Diseases

National Center For Advancing Translational Sciences

Investigators

Abstract

The Functional Genomics Laboratory (FGL) partners with extramural investigators to apply high-throughput functional screening technologies—such as CRISPR-based perturbation, RNA interference (RNAi), and small molecule screening—to identify disease-relevant targets and advance therapeutic discovery. By integrating these tools with biologically meaningful cell models, we aim to generate functional data that directly supports translational research goals. Our vision is to use functional genomics to uncover the molecular basis of human diseases and accelerate the development of targeted therapies. Through these collaborations, we offer end-to-end support—from assay development and screening execution to data analysis, interpretation, and follow-up validation. FGL supports a wide range of collaborative projects across disease areas. For example, we have used CRISPRi and small molecule screening in iPSC-derived neuronal models to identify therapeutic targets and candidate compounds for Niemann-Pick Type C1 (NPC1). In another collaboration, we screened FDA-approved compounds in CRISPR-edited reporter cells to discover potential treatments for sickle cell disease. Additional project areas with extramural partners include cancer (e.g., drug enhancer/resistance screens, discovery of molecular targets, and development of 3D metastasis models) and infectious diseases (e.g., studies of viral infection and replication in the context of Zika virus, HIV, Ebola virus, and Hepatitis C virus). These collaborations enable both sides to combine resources and expertise to tackle complex scientific questions that may not be addressable in isolation. Through these efforts, the Functional Genomics Laboratory helps advance NCATS’s mission to catalyze translational science by supporting collaborative, high-impact research that brings us closer to effective therapies for a wide range of diseases. Public Health Impact Statement The Functional Genomics Laboratory advances public health by partnering with extramural investigators to identify novel therapeutic targets and accelerate the development of treatments for both rare and common diseases. Through the use of high-throughput screening technologies and disease-relevant models, we help uncover the molecular drivers of disease and support the discovery of new therapeutic strategies. By enabling collaborative, translational research across a wide range of conditions—including cancer, genetic disorders, and infectious diseases—our work contributes to the development of more effective, targeted, and timely interventions that address critical unmet medical needs.