Press Release | January 30, 2025

Sapient Contributes to Landmark Study Published in Science Linking Lysosomal Biology and Oxysterol Metabolism to Pulmonary Arterial Hypertension (PAH)

January 30, 2025 – San Diego, CA – Sapient, a leader in multi-omics discovery, has contributed to compelling new research published in Science which links lysosomal biology and oxysterol metabolism to pulmonary arterial hypertension (PAH) pathobiology. The multi-omics study, led by researchers at the University of Pittsburgh School of Medicine and for which Sapient provided mass spectrometry-based discovery metabolomics data, identified a nuclear receptor called NCOA7 that acts as a primary controller of lysosomal activity and sterol homeostasis. Through integrative analysis of large-scale genomics and metabolomics datasets, the researchers found that NCOA7 deficiency has genetic predisposition and promotes lysosomal dysfunction as well as the production of proinflammatory oxysterols and bile acids which trigger endothelial cell (EC) immunoactivation.

An unbiased, metabolome-wide association study across 2,756 PAH patients showed that NCOA7-dependent oxysterols and bile acids were associated with PAH mortality, establishing causative linkages between these metabolites, EC inflammation, and PAH. Of key importance, the researchers were able to synthesize an activator of NCOA7 that promoted lysosomal activity, prevented EC immunoactivation, and reversed PAH in a rodent model. The findings have significant implications for diagnostic and therapeutic development for PAH, a rare but serious condition characterized by vessel remodeling in the lungs that in turn strains the heart.

“This research establishes that NCOA7 acts as a sort of biological ‘brake’ on inflammation in the lining of blood vessels, and underscores the clinical importance of this mechanism in controlling PAH disease severity as well as the severity of possibly many other immune and inflammatory disorders,” said Stephen Chan, MD, PhD, principal investigator of the study, Vitalant Chair in Vascular Medicine, and Director of the Vascular Medicine Institute at University of Pittsburgh School of Medicine. “The potential of these findings to improve prognosis and guide more targeted therapies is truly exciting.”

“We are thrilled to have had the opportunity to collaborate with this incredible group of researchers and contribute metabolomics data and analytical insights to enable this landmark work,” said Mo Jain, MD, PhD, Founder and Chief Scientific Officer and a contributing author to the study. “The findings highlight the power of nontargeted metabolomics to elucidate mechanisms of disease, and exemplifies the value of multi-omics profiling to understand both genetic and metabolic paradigms of disease.”

The full paper, entitled “Lysosomal dysfunction and inflammatory sterol metabolism in pulmonary arterial hypertension”, can be accessed here.

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About Sapient

Sapient is at the forefront of biomarker discovery, utilizing cutting-edge, high-throughput mass spectrometry and biocomputational frameworks to offer unparalleled multi-omics data generation and analysis. By enabling comprehensive biomarker-phenotype mapping across thousands of biosamples, Sapient empowers biopharma sponsors to advance precision drug development beyond genomic insights. The company’s proprietary Human Biology Database — comprising data from tens of thousands of samples — enables rapid drug target identification, biomarker discovery and validation, and translational insights across all stages of drug development. For more information, visit sapient.bio.

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