Janssen-Heininger, Anathy & Team's Study Demonstrates Potential Lung Fibrosis Therapy

July 11, 2018 by Jennifer Nachbur

New translational research led by UVM Professor Yvonne Janssen-Heininger, Ph.D., demonstrates a novel biological therapeutic candidate for regressing pulmonary fibrosis in a difficult-to-treat preclinical model of the disease, providing much-needed hope for the roughly 150,000 Americans suffering from this devastating condition.

Yvonne Janssen-Heininger, Ph.D., UVM Professor of Pathology & Laboratory Science. (Photo: Medical Communications)

New translational research, published in Nature Medicine, demonstrates a novel biological therapeutic candidate for regressing pulmonary fibrosis in a difficult-to-treat preclinical model of the disease, providing much-needed hope for the roughly 150,000 Americans suffering from this devastating condition.

A chronic, progressive disease marked by lung scarring that impedes breathing and the flow of oxygen to the bloodstream, idiopathic pulmonary fibrosis (IPF) results in approximately 40,000 deaths each year in the U.S. alone. Believed to be associated with aging, the disease is diagnosed annually in approximately 40,000 individuals between 40 and 70 years of age. Survival is typically only three to five years after diagnosis.

This study included an examination of IPF patient lung tissue, transgenic mouse models and direct administration of a therapy based off an enzyme called glutaredoxin-1 – or GLRX – to the airways of murine models of IPF. GLRX repairs damaged proteins and is inactivated in the lungs of IPF patients and results in poor lung function. Senior study author Yvonne Janssen-Heininger, Ph.D., and first author Vikas Anathy, Ph.D., of the University of Vermont’s Larner College of Medicine, and colleagues are inventors on a patent for GLRX, granted to the University of Vermont.

Though the exact mechanisms responsible for IPF have yet to be determined, oxidative stress is believed to play a critical role in modifying and altering the function of proteins or enzymes in various diseases, including IPF. However, the therapeutic potential for reversing the oxidative stress mediated modification of proteins was unknown. Janssen-Heininger and colleagues have discovered that GLRX is capable of reversing the oxidation of proteins, preventing the death of lung cells and ultimately, regressing pulmonary fibrosis in experimental models. The researchers believe that these positive effects raise the potential of GLRX as a therapeutic agent for IPF, which currently has limited treatment options.   

“This provides a strong rationale to develop inhaled glutaredoxin as a possible therapy for patients with lung fibrosis,” says Janssen-Heininger. She and the study authors state that further investigation will be needed to gain a deeper understanding of the activity associated with GLRX.

In addition to Janssen-Heininger and Anathy, coauthors on the study include: Karolyn Lahue; David Chapman; Shi Chia; Dylan Casey; Reem Aboushousha; Jos van der Velden; Evan Elko; Sidra Hoffman; David McMillan; Jane Jones; James Nolin; Sarah Abdalla; Robert Schneider; David Seward; Elle Roberson; Matthew Liptak; Morgan Cousins; Kelly Butnor; Douglas Taatjes; Ralph Budd; Charles Irvin; Ye-Shih Ho; Razq Hakem; Kevin Brown; Reiko Matsui; Markus Bachschmid; Jose L. Gomez; Naftali Kaminski; and Albert van der Vliet.

This therapy is being developed in collaboration with Celdara Medical, LLC, of Lebanon, N.H. and with support from the National Heart, Lung and Blood Institute of the National Institutes of Health under award numbers R44 HL129593-01 and R35HL135828.

Of note:

Congratulations to Dr. Arti Shukla, co-author on the manuscript "Extracellular Vesicle and Particle Biomarkers Define Multiple Human Cancers" published in the journal Cell. Read the paper

Please join Dr. Yvonne Janssen-Heininger in congratulating Wyatt Chia on his successful thesis defense. Congratulations, Dr. Wyatt Chia, Ph.D.!!!

Please join Dr. Vikas Anathy in congratulating Nicolas Chamberlain and Dr. Emily Nakada.

Nicolas Chamberlain a PhD student recently published a paper entitled “Lung epithelial protein disulfide isomerase A3 (PDIA3) plays an important role in influenza infection, inflammation, and airway mechanics” in the journal Redox Biology (PMID 30735910). His abstract to be presented at the American Thoracic Society (ATS) conference was chosen to receive an abstract scholarship. The scholarship includes a full in-training registration to the 2019 ATS International Conference in Dallas, Texas. 

Dr. Emily Nakada was a post-doctoral fellow in our group. Her manuscript entitled “Conjugated bile acids attenuate allergen-induced airway inflammation and hyperresposiveness by inhibiting UPR transducers” has been recently accepted in the journal JCI Insight.


Please join Dr. Yvonne Janssen-Heininger in congratulating Allison Manuel and Evan Elko.

Dr. Allison Manuel is a post-doctoral fellow in our group.  Her abstract to be presented at the American Thoracic Society conference was chosen to receive an Abstract Scholarship . The scholarship includes a full In-Training Registration to the 2019 ATS International Conference in Dallas, Texas.  

Evan Elko is a PhD student. He just received notice that his F31 NIH application entitled: “Role of peroxiredoxin-4 in Idiopathic Pulmonary Fibrosis”  will be funded. 

Congratulations to Evan and Allison. 


Christopher Dustin and Caspar Schiifers, students in Dr. Albert van der Vliet's lab, each won a Young Investigator Award for their presentations at the SRFBM conference in Chicago. (Nov 2018)

SRFBM conference 2018

[photo left to right: students:C. Dustin, C. Schiffers, SRFBM president F. Domann, principal investigator A. van der Vliet]


Terri Messier, Research Analyst and Lab Manager of the Cunniff lab was recently awarded a Dean's Excellence in Research Award from the Larner College of Medicine. Terri has served the UVM community for over 25 years both as a scientist and steward of professionalism. Terri is a rigorous, creative and skilled scientist. She has authored 18 manuscripts, contributed to numerous patent applications and mentored an abundance of students. Terri serves on the UVM Laboratory Safety Partnership, the Youth Workforce Development Grad Challenge and is a member of the Vermont Biosciences Alliance. Terri is actively involved in the larger Chittenden county community, directing the Vermont Cancer Center Community Outreach Program that brings high school students into LCOM research labs and provides them with early exposure to science and research. Terri is a driving factor in the continuing success of our research and a role model for a dedicated and professional research scientist. Congratulations Terri!!

Congratulations to Dr. Yvonne Janssen-Heininger, Ph.D. on her selection as a new Fellow of the Society for Redox Biology and Medicine (SfRBM) in recognition of her outstanding contributions in the field of redox biology and to SfRBM. (Sep 2020)

From Yvonne Janssen Heininger, Ph.D.: nine members from the VLC/RBP group traveled to Ventura, CA to attend the Gordon Research Conference/Seminar on Oxygen Radicals that I organized together with Dr. Manisha Patel from Denver.


Congratulations to Cheryl van de Wetering who organized a highly successful Gordon Research Seminar on Oxygen Radicals: "Redox Processes from Chemical Reactivity to Their Role in Health and Disease" in Ventura CA February 1-2 2020.

Trainees from all over the world gathered, and gave oral and poster presentations along with elevator pitches in their work in redox biology. Cheryl also organized two keynote lectures held by leaders in our field. She single handedly did the fund raising and obtained grants that allowed her to reimburse travel and registration for the trainees. Congratulations to Cheryl on a job performed with the highest level of professionalism!

Congratulations also go to Dr. Allison Manuel. Allison won a GRC 2020 Mini-Bolt Award for the best elevator pitch of the conference!


A special note of thanks to Dr. Albert van der Vliet who designed the Mini-Bolt Awards in line with the Iron Bolt Award that accompanies this conference. Albert started a new tradition in this GRC.



The Cunniff Lab recently received funding from the Butler Family Foundation (managed by the Community Foundation for the Greater Capital Region) to investigate malignant mesothelioma tumor profiles that may predict sensitivity to therapies currently being developed in the Cunniff Lab, with support from RS Oncology. Malignant mesothelioma is a devastating disease that has no cure and is one of the most difficult tumors to treat. RS Oncology, in collaboration with the Cunniff Lab, is developing a therapeutic approach utilizing a novel mechanism of action that has shown promising pre-clinical activity.

This generous gift from the Butler Family will help to identify patients who are most likely to respond to current and new therapies under development. We are very thankful to the Butler Family for their generous support!




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