National Center for Advancing Translational Sciences

Genotype-specific molecular and functional trajectories in NGLY1 deficiency: a comparative multi-omics study of patient-derived iPSC neurons

Background NGLY1 deficiency is an ultra-rare congenital disorder of deglycosylation with prominent neurodevelopmental impairment and marked allelic heterogeneity. Prior human neuronal models have characterized NGLY1 loss largely within single genetic backgrounds, leaving open whe...

Integrating in silico ADME modeling with Tox21 toxicity profiling to support compound prioritization

Abstract Toxicity remains a leading cause of late-stage attrition in drug development and is heavily influenced by a compound’s ADME (Absorption, Distribution, Metabolism, and Excretion) properties. The ability of a molecule to reach its target tissue, persist in circulation, or...

Advances in 3D Bioprinting for Breast Cancer Modeling: Tumor Microenvironment, Metastasis, and Drug Screening

The tumor microenvironment (TME) is a complex and heterogeneous milieu encompassing biological and biochemical events and diverse physical, chemical, and mechanical interactions between tumor and stromal cells. This heterogeneity plays a pivotal role in regulating tumor progressi...

RNF5 Regulates HERP1 and OS9 Stability and Modulates Processing of an ERAD Substrate

Endoplasmic reticulum-associated degradation (ERAD) must dynamically adapt to cellular protein-folding demands, yet mechanisms regulating ERAD-associated adaptors remain incompletely defined. Here, we identify the E3 ubiquitin ligase RNF5 as a regulator of the ERAD adaptors HERPU...

Integrating Tox21 Assay Data and Chemical Fingerprints for Neurotoxicity Prediction

Abstract Exposure to environmental and pharmaceutical chemicals presents a significant risk for neurotoxicity. To reduce reliance on in vivo testing, the U.S. Toxicology in the 21st Century (Tox21) consortium has generated quantitative high-throughput screening data for approxima...

Therapeutic NAMPT inhibition reveals a targetable metabolic vulnerability in neuroblastoma

Abstract Background Neuroblastoma (NB) remains a major cause of pediatric cancer mortality for which new therapeutic strategies are needed. Exploitation of reprogrammed metabolic pathways offers an opportunity for cell-type specific anticancer therapeutics. To identify pediatric...