Antioxidant therapies may hold promise for the nearly 25 million Americans suffering from asthma, and additional 140,000 people diagnosed with pulmonary fibrosis, but to date, determining exactly how to modify them into a feasible treatment has proved challenging.
Yvonne Janssen-Heininger, Ph.D., Professor of Medicine, Larner College of Medicine at UVM. (Photo: LCOM Design & Photography)
Antioxidant therapies may hold promise for the nearly 25 million Americans suffering from asthma, and additional 140,000 people diagnosed with pulmonary fibrosis, but to date, determining exactly how to modify them into a feasible treatment has proved challenging.
As the inaugural recipient of the Outstanding Investigator Award (OIA) from the National Heart, Lung and Blood Institute (NHLBI), Yvonne Janssen-Heininger, Ph.D., professor of pathology and laboratory medicine at the Larner College of Medicine at the University of Vermont, says this award will facilitate her “vision” to fully translate her research findings into clinical care.
This prestigious award will provide more than $900,000 in annual funding for a total of roughly $6.3 million over the award’s seven years. The NHLBI Outstanding Investigator Award is designed “to promote scientific productivity and innovation by providing long-term support and increased flexibility to experienced Program Directors (PDs)/Principal Investigators (PDs/PIs) who are currently PDs/PIs on at least two NHLBI R01-equivalent awards and whose outstanding record of research demonstrate their ability to make major contributions to heart, lung, blood and sleep research.”
“I’ve devoted my entire career to antioxidant-related research,” says Janssen-Heininger. “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.”
According to Janssen-Heininger, oxidants are molecules that play an important role in remodeling lung tissue in patients with asthma, chronic obstructive pulmonary disease (COPD), and pulmonary fibrosis – a disease marked by scarring in the lungs that usually affects people ages 50 to 75. While experimental antioxidant therapies to date have failed, she and her team have a clue as to the culprit. Their discovery – that oxidants can effectively change the function of the chemical messengers in the cells of the lung by adding an antioxidant molecule called glutathione via a process known as protein S-glutathionylation – could translate into successful therapies.
“Glutathione is an antioxidant molecule, traditionally thought to be good for you,” she explains. “Via this new chemistry, we believe it is actually relevant to the development of a scar.”
Since severe asthma, COPD and pulmonary fibrosis involve scarring, she and her team wondered if interfering with the systems that impact S-glutathionylation could stop the scarring process from occurring.
Over the past several years, Janssen-Heininger and her team have earned multiple NIH R01 awards, as well as a Fast Track Small Business Innovation Research (SBIR) grant with Lebanon, N.H.-based Celdara Medical, LLC. Over the last 10 years, Janssen-Heininger has also worked with UVM Innovations to build a portfolio of intellectual property that now includes two issued patents related to the oxidant-controlling enzyme glutaredoxin. One is focused on its use as a therapeutic compound for patients with pulmonary fibrosis and other diseases, and the other as a diagnostic tool for detecting certain forms of oxidized proteins in tissues.
“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,” says Janssen-Heininger.
In addition to the NHLBI OIA, Janssen-Heininger recently received news of her team’s receipt of an NIH SMART (sequential, multiple assignment, randomized trial) program grant, which provides regulatory support to fast-track the development of her treatment for pulmonary fibrosis, and – if successful – would make it the first in its class for treating this disease.