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Liver disease researchers and clinicians at the 51��Ʒ��Ƶ School of Medicine and UPMC will use a $7.8 million grant to create a new drug discovery center called the 51��Ʒ��Ƶ Translational Center for Microphysiology Systems. The funding was announced this month by the National Center for Advancing Translational Sciences (NCATS), part of the National Institutes of Health. The investigators will use human “liver-on-a-chip" systems in collaboration with the Food and Drug Administration to improve drug discovery and development.

Organs-on-chips, also called microphysiology systems (MPS), replicate the physiological environment and functions of human organs. They can be used to predict drug responses in disease models and to evaluate drug safety while reducing reliance on animal testing. The center, managed within the 51��Ʒ��Ƶ Drug Discovery Institute, will “qualify” human livers-on-chips as drug discovery tools and submit the results to the FDA for approval. 

“The center benefits from the recent implementation of the FDA Modernization Act 2.0 that emphasizes alternative approaches, including MPS, to traditional testing with animals for predicting drug safety before starting human clinical trials,” said Alejandro Soto-Gutierrez, director of the Center for Transcriptional Medicine and a professor of pathology.

The initial focus of this research will be on toxicology, drug testing and selection of patient cohorts in clinical trials for metabolic dysfunction-associated steatotic liver disease (MASLD), a heterogeneous disease that affects 25-30% of the world population and has yet to have a drug approved by the FDA. Drugs now in development will help only a small percentage of patients, indicating that this disease requires a precision medicine approach.

“We are honored to have been selected as one of four translational centers in the country to receive this funding,” said D. Lansing Taylor (pictured above), the contact principal investigator, who is the director of the Drug Discovery Institute and Allegheny Foundation Professor of Pharmacology. “We will pursue a precision medicine approach in the qualification of our liver MPS considering patient genetic and lifestyle/environment characteristics in our analyses,” he said.

The other principal investigators include Mark Miedel, an assistant professor of pathology and member of UPDDI, and Mark Schurdak and Lawrence Vernetti, both associate professors of in 51��Ʒ��Ƶ’s Department of Computational and Systems Biology and members of the Drug Discovery Institute. All are also members of the 51��Ʒ��Ƶsburgh Liver Research Center.

The starting point for the research is de-identified patient clinical data and blood samples collected from patients enrolled in the UPMC Liver Steatosis and Metabolic Wellness Program, directed by Jaideep Behari. 

“Patients will benefit from the innovative precision medicine approaches for diagnosis and treatment of MASLD, a complex, multisystem disorder with a highly variable course, applied in the new center via harnessing the qualified liver MPS,” said Behari.