Outstanding Investigator Award Goes to Professor for Lung Disease Antioxidant Studies

The National Heart, Lung and Blood Institute (NHLBI) has named the recipient of its inaugural Outstanding Investigator Award: Yvonne Janssen-Heininger, PhD, professor of pathology and laboratory medicine at the Larner College of Medicine at the University of Vermont, to conduct studies on antioxidant therapies for lung diseases, including chronic obstructive pulmonary disease (COPD).

Yvonne Janssen-Heininger, PhD. Photo credit: Larner COM Design & Photography

The award, which will provide over $900,000 in annual funding for a total of $6.3 million over seven years, promotes “scientific productivity and innovation by providing long-term support and increased flexibility to experienced program directors or principal investigators” who are currently on at least two NHLBI awards “and whose outstanding record of research demonstrate their ability to make major contributions to heart, lung, blood and sleep research.”

Janssen-Heininger said the award will help take her her research into clinical care.

Part of the altered alveolar environment in lung fibrosis involves oxidative stress that is driven by an imbalance between oxidant production and antioxidant defenses, and while experimental antioxidant therapies have been tested in studies, so far they have been unsuccessful. But Janssen-Heininger and her colleagues have an idea as to the culprit.

“I’ve devoted my entire career to antioxidant-related research,” Janssen-Heininger said in a news release. “Our field has been turned upside down in recent years. While originally, oxidants were believed to be ‘bad guys,’ it turns out that oxidants may work in a very different way to cause disease. Similarly, some antioxidants that are generally believed to be ‘good guys’ may in fact contribute to disease in a surprising manner.”

The team discovered that oxidants can change the function of chemical messengers in lung cells through the addition of a molecule called glutathione through a process known as protein S-glutathionylation.

“Glutathione is an antioxidant molecule, traditionally thought to be good for you,” Janssen-Heininger said. “Via this new chemistry, we believe it is actually relevant to the development of a scar.”

The team wondered if interfering with the systems that impact S-glutathionylation could stop lung scarring from occurring.

“The goal of our research is to better understand how this process of S-glutathionylation works, and whether the enzymes that regulate this process can be a target for more specific drugs to combat tissue fibrosis,” Janssen-Heininger said.

She and her collagues have been awarded multiple R01 awards from the National Institutes of Health (NIH) and a Fast Track Small Business Innovation Research (SBIR) grant from the company Celdara Medical.

Janssen-Heininger has also worked with UVM Innovations to build a portfolio of intellectual property, including two patents related to the oxidant-controlling enzyme glutaredoxin. One of the issued patents is focused on glutaredoxin’s use as a therapeutic compound for patients with pulmonary fibrosis and other diseases. The other is for glutaredoxin as a diagnostic tool for detecting certain forms of oxidized proteins in tissues.