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Fall 2010

Damage Control

Njoku's research aims to prevent liver injury from oft-used drugs.

By: Mary Beth Regan
Date: October 1, 2010

Dolores B. Njoku

Dolores B. Njoku, a pediatric anesthesiologist, was at a critical juncture in her research on drug-induced, immune-mediated liver injury and contemplating her options one morning last February. With snow piled up outside, her computer indicated a waiting message. That’s when she learned she’d been awarded the William F. Rienhoff Jr. MD Scholar Award for 2011-2013, named for a Hopkins pioneer in thyroid research and lung cancer surgery.

The timing couldn’t have been more perfect. “We are on the verge of some very important breakthroughs,” says Njoku, whose work examines how drugs—including antibiotics, anti-seizure medications, nonsteroidal anti-inflammatory drugs, and halogenated anesthetics—cause autoimmune reactions, which can lead to liver injury and even death. While such injuries have long been documented, the mechanisms for the reactions have been poorly understood.

The $40,000 stipend will enable Njoku to move forward with testing preventive therapeutic options. 

In 2005, Njoku opened the door for understanding the pathways in the liver-injury process when she published results of her work with a mouse model that mimicked the drug reaction in the liver.

Njoku now understands that some drugs produce haptens, which bind to and change the proteins in the liver. As a result, the proteins are no longer recognized by the body, and a self-attack occurs. Symptoms include fatigue, rash, elevation of liver enzymes, liver injury, and death. One suspected pathway: immunoglobulin G4 (IgG4). In tests she found that mice lacking the IgG4 pathway did not develop the anesthetic-induced liver damage.

“So we are beginning to understand the mechanism,” says Njoku, “but we are a long way from solving the problem.” Next, Njoku will focus on understanding these autoimmune-reaction triggers, whether genetic or environmental, and test therapeutic options to prevent reactions.

She will move forward with analyzing a bank of human serum samples for clues about autoimmune responses to altered drug-metabolizing enzymes involved in the initiation of abnormal immune responses. It’s these responses that culminate in liver injury. The findings could be pivotal: They could serve as noninvasive biomarkers to assist in identifying patients at risk for adverse reactions, and aid in developing vaccines that would promote tolerance to specific drugs.

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