Vermont Medicine Magazine

From Holland to Burlington
Janssen-Heininger’s research career began early, as an undergraduate student at the University of Limburg in Maastricht, The Netherlands. She studied biological health sciences, investigating coal miners’ lung diseases while earning her bachelor’s and master’s degrees. She earned a Ph.D. at Maastricht University, The Netherlands, in alliance with Maastricht University Medical Center. At a conference in Canada in 1989, when Janssen-Heininger was a doctoral student, her Dutch mentor introduced her to Brooke Mossman, Ph.D., now professor emeritus of pathology and laboratory medicine at UVM and a University Distinguished Professor. Mossman invited Janssen to collaborate on a three-month research project at UVM.

“I had no idea what I was getting into. Three months turned into five months, one year into two years. I went back and forth to Maastricht working on my Ph.D. research. My intention was always to go back to Holland to support research at my alma mater,” Janssen-Heininger said.

And then life happened. She met her future husband, Peter Heininger, a Lake Champlain ferryboat captain, at the Old Dock House ferry stop in Essex, N.Y., when he crashed the graduation party she was attending. Janssen-Heininger completed her Ph.D. in 1993, and the couple married in 1996, the same year she was offered a faculty position at UVM.

Janssen-Heininger completed her postdoctoral training in UVM’s pathology department under a Parker B. Frances Foundation fellowship in pulmonary research. She progressed through the faculty ranks, starting as a research assistant professor and becoming a full professor in 2008. From 2017 to 2021, she was vice-chair for research for the Department of Pathology and Laboratory Medicine. She received the inaugural National Heart Lung and Blood Institute R35 Outstanding Investigator award and was named the 2017 Larner College of Medicine Research Mentor and the College’s 2021 Research Laureate.

Janssen-Heininger settled into life in Vermont with her husband, raising a son, Skyler, and daughter, Meara, now 20 and 23 years old, respectively.

Janssen-Heininger did return to her alma mater, in a way: In 1997 she initiated and helped build an affiliation between the UVM and University of Maastricht, establishing an exchange program for graduate students. This ongoing alliance has provided a means for scientific knowledge exchange and allowed for more competitive research grant applications. Since 1999, Janssen-Heininger has been an adjunct professor for the Department of Pulmonology at the University of Maastricht. Many doctoral students and post-doctoral fellows working in the Janssen-Heininger Laboratory have been affiliated with the University of Maastricht.

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Collective Approach
Janssen-Heininger’s scientific discoveries have focused on the pathways that regulate fibrotic tissue, bridging the gap between basic biochemistry and the development of new therapeutics to combat pulmonary disease. She holds five U.S. patents for systems and methods to determine oxidized proteins and treating oxidative stress conditions, and the Janssen-Heininger Laboratory works to advance these as potential drugs to treat fibrotic lung diseases.

She is dedicated to training the next generation of scientists: To date, Janssen-Heininger has supervised nearly 30 graduate students, more than 10 postdoctoral fellows, and nine undergraduate students. She strives to provide an exciting research environment and extensive mentoring for laboratory members to enable each of them to be successful in the biomedical science arena. Dozens of her trainees have advanced to successful academic careers, including several faculty members at the Larner College of Medicine who are tenured and have secured independent funding, due in large part to her critical mentorship.

“Yvonne is a really supportive mentor and a good example to follow, both scientifically and in terms of career development,” said postdoctoral fellow Elizabeth Corteselli, Ph.D. “It’s a very collaborative environment. Our projects are all different but related, and we all help each other out.”

The lab’s faculty scientist, Reem Aboushousha, Ph.D., began in the lab as a technician in 2015, continuing as a doctoral student under Janssen-Heininger’s mentorship. Her dissertation research focused on metabolic reprogramming and redox perturbations in asthma. Aboushousha now investigates treatments for cancer.

“I am working on a unique new pathway that unravels how cancer cells develop resistance to chemotherapy. It’s relevant to many cancer types that we see people struggling with. We are working with other UVM investigators, here and also in the chemistry department, to develop compounds to test our hypotheses,” Aboushousha said.

The Janssen-Heininger Lab team, which also includes two undergraduate students and four technicians, partners with clinical investigators in other laboratories, including chemists, biochemists, cell biologists and physiologists. Janssen-Heininger works closely with fellow pathology and laboratory medicine faculty and UVM Cancer Center members, including Adrianus (Jos) van der Velden, Ph.D., Vikas Anathy, Ph.D., Brian Cunniff, Ph.D., Albert van der Vliet, Ph.D, and David Seward, M.D., Ph.D. Their collaborations have produced numerous academic publications, innovations, and drug candidates.

Janssen-Heininger envisions a University of Vermont Institute for Redox Medicine, incorporating multiple domains of expertise to advance technologies and drug development efforts without relying solely on federally-funded grants.

“Our collaborative expertise makes us better able to advance discoveries and drug development efforts. There’s tremendous opportunity for us to develop new drugs to change the course of disease,” Janssen-Heininger said. “Our group has several patents ripe for further development, and we are ready to expand these endeavors. One compound, developed in our program by Dr. Cunniff and Nicholas Heintz, Ph.D., professor emeritus, is currently in a Phase 1 clinical trial for patients with malignant mesothelioma, a lethal cancer of the lining of the lung.”

Divergent Thinking
Research related to counteracting cellular damage caused by oxygen has lately gained acceptance as a basis for novel therapeutic approaches, and Janssen-Heininger’s work is in the forefront of this research. But it was not always this way: Redox biology was not well-recognized in the 1990s, and Janssen-Heininger struggled to gain credibility.

“I have been working in a very niche area of oxidant biology for 30 years, and it’s [only now] becoming front and center. [In the early 1990s], this oxidative process was considered irrelevant. At conferences, other scientists told me, ‘This can’t happen, Yvonne, it is not chemically possible,’’’ she recalls. “These same scientists are now asking me about this and backing me up.” She went from being not taken seriously to being considered an expert in her field.

To gain recognition, getting published in high-impact journals became her mission. In 2009, when her paper on redox amplification of apoptosis was rejected by the Journal of Cell Biology, she made a phone call to the editor to protest and explain why the paper should be published. The campaign worked: The editor sent Janssen-Heininger’s paper back out for review, leading not only to its publication but also an editorial highlight written by that same editor.

The redox biology and pathology program Janssen-Heininger built at UVM has increased understanding of redox-based mechanisms in the pathology of chronic disease and developed novel diagnostic tools. Program investigators are funded through National Institutes of Health research grants, private and public foundation grants, and through sponsored research contracts with biotech-pharma and small businesses. The program strongly supports UVM’s efforts to improve undergraduate, graduate, and medical student education in the biomedical sciences, as well as postdoctoral training in basic and clinical research. Many junior investigators in the program have become distinguished scientists, serving in research and faculty positions at academic institutions across the nation and around the world.

From Bench to Bedside and Back
Jointly with Jos van der Velden, the lab has heavily invested in organoids, which are tiny, three-dimensional tissue cultures produced in vitro from stem cells. They disassemble pieces of diseased human lungs into individual cells and grow them in a culture. The cells reassemble into “mini-lungs” that enable researchers to study mechanisms of lung fibrosis and explore therapeutic opportunities. Precision-cut lung slices, thin slivers made from live tissue with all of its components, allow for examining and exposing lung tissues to potential therapeutics in settings as close to reality as possible.

“We work with human lung samples from patients with pulmonary fibrosis. It emphasizes how the mechanisms we study in our research relate to the actual disease progression in these patients,” said Corteselli, the post-doctoral fellow.

Much of the tissue comes directly from patients at the UVM Medical Center, some of whom Jannsen-Heininger and Corteselli have met. Lab members have attended support groups for patients with idiopathic pulmonary fibrosis or interstitial lung disease, where they discuss their research and interact with people with lung diseases and their caregivers.

“I have been humbled to meet people with pulmonary diseases and learn about their experiences and questions they have about their condition. This connection is so important to me and the fellows in my lab. Knowing that patients are thankful for the research we do is what keeps us going forward through difficult times and failures,” Janssen-Heininger said.

“I’ve had folks say to me, ‘upon my death, I will donate my lungs to your research.’ My clinical colleagues in the Department of Pathology and Laboratory Medicine have been able to do rapid autopsies, sometimes even on weekends. It’s an important opportunity to see what happens in the lung. It can also be a very difficult experience. This lung that somebody gave me, someone whom I met a number of times, allows me to make these discoveries. This is the ultimate gift.”