Jason Eng, MD, PhD

Pilot Research Award
$50,000 over one year

The Ohio State University

Targeting CD38 to Enhance Liver Regeneration

The liver is one of the few organs capable of regenerating after injury. Recovery from severe conditions depends heavily on the ability of liver cells to divide and restore lost tissue. Patients who develop liver failure from causes including acetaminophen overdose, trauma, or disruption of the liver’s blood supply often require emergency liver transplantation to survive. Even the success of a liver transplant relies on the ability of the donor organ to successfully regrow following the stress of the surgery or from procedures requiring removal of organ segments. Our studies have identified an important role for a protein called CD38, which is found on nearly all liver cells and helps regulate the injury response. CD38 is located on the cell surface as well as within internal cellular compartments. It controls levels of nicotinamide adenine dinucleotide (NAD+), a molecule essential for energy production, metabolism, stress resistance, and cell division. CD38 also regulates calcium signaling within cells, which can trigger inflammation and cell death. In previous experiments, blocking CD38 with a specialized drug protected both mouse and human liver cells from damage caused by low oxygen conditions. These findings led us to question whether inhibiting CD38 could also improve the ability of the liver to regenerate after severe injury. Using mouse models along with advanced liver cell and tissue culture systems, we will examine whether blocking CD38 after chemical injury or a liver surgery enhances tissue regeneration. Further, we will determine whether blocking CD38 preserves NAD+ levels, maintains cell metabolism, and supports liver cell proliferation during recovery. This work may uncover new means that control liver regeneration and identify a potential strategy to help patients recover from acute liver injury without requiring further organ transplantation.