LCOM & Department News

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.

 

Past Department Highlights

Congratulations to Anne Stowman, M.D., assistant professor of pathology and laboratory medicine, on accepting the position as Network Vice Chair for Anatomic Pathology. (3/2024)  

Congratulations to Ashley Volaric, M.D., assistant professor of pathology and laboratory medicine, on receiving a Physician-Scientist Pilot Award through the Translational Global Infectious Disease Research (TGIR Group) for her research on Epstein-Barr virus (EBV) epigenetics of diffuse large B-cell lymphomas in sub-Saharan Africa. (3/2024)

Congratulations to Rebecca Wilcox, M.D., associate dean for faculty affairs, and professor of pathology and laboratory medicine, on receiving The Polaris Award for Outstanding Mentorship, and Dr. Yvonne Janssen-Heininger, Ph.D., on receiving the Gender Equity Outstanding Achievement in Medicine & Science Award at the 5th Annual Celebration of Gender Equity in Medicine and Science Awards. This award honors a Larner College of Medicine faculty or staff member who provides outstanding formal or informal mnetorship for women or gender diverse** college community members. Dr. Wilcox was nominated by Andrea Green, Julie Dumas, Alexandra Kalof, and LE Faricy. (2/2024) **Gender diverse refers to those who identify with a gender outside of the she/her, he/him binary   

Congratulations to Dr. Brian Cunniff, Ph.D., assistant professor of pathology and laboratory medicine, the team in the Cunniff Lab, and industry partner , RS Oncology, on having their novel therapy enter Phase 2 Clinical trials. Read more here Milestone for UVM-developed cancer drug. (2/2024)

During the annual Larner College of Medicine's Foundations Award Celebration, Amer Abu Alfa, M.D., assistant professor of pathology and laboratory medicine received The Dean Warshaw Integration Award recognizing the faculty member whose teaching best captured the spirit of the Vermont Integrated Curriculum. Congratulations. Christina Wojewoda, M.D., professor of pathology and laboratory medicine and vice chair for education pathology, presented the Ephraim Woll Award for Excellence in General Pathology to John Rustad. (2/2024) 

Congratulations Dr. Bei Zhang, M.D., M.S., Ph.D., MLS(ASCP)CM, on January 17, 2024, is to receive the Educational Scholarship Award from the Teaching Academy Awards for Teaching and Educational Excellence. This award recognizes an individual who has demonstrated a record of Quality, Quantity, and Engagement in medical education scholarship. Dr. Zhang, M.D., M.S., Ph.D., MLS(ASCP)CM, has been advanced to Distinguished Educator by the Teaching Academy at LCOM. Congratulations also to Bronwyn Bryant, M.D., for advancing to the level of Master Teacher and Agnes Balla, M.D., on being inducted as a Member. (1/2024)

Congratulations to University Scholar Mary Cushman, M.D., M.Sc., professor of medicine and pathology and laboratory medicine, on being ranked #90 in the U.S. and #144 in the world as one of the Best Female Scientists in the World, by Research.com. Also, Dr. Cushman, M.D., M.Sc., recently delivered the Robert Reneman Lecture at the Cardiovascular Research Institute Maastricht (CARIM)'s 2023 symposium in The Netherlands. The tile of her talk was "Stroke and Cognitive Impairment in a Biracial U.S. Cohort: The REGARDS Study." (1/2024)

In a recent Nature Methods paper, Doug Taatjes, Ph.D., Director of the Microscopy Imaging Center, and the Center for Biomedical Shared Resources at the Larner College of Medicine, together with colleagues from the international consortium QUAREP-LiMi, proposed a set of standardized community-developed checklists to assist researchers, reviewers, and journal editors with the goal of increasing the clarity and reproducibility of image figures and their analyses. The hope is that many journals will adopt these guidelines as part of their “Instructions for Authors”—providing a succinct and easy to use checklist for authors when compiling images for reproduction and descriptions of image analyses performed. (11/2023) (from the LCOM Newsletter)

Congratulations to some of our residents and our fellowship student on having their abstracts accepted for the upcoming 2024 USCAP annual meeting in March. "Unexpected Cardiac Amyloidsis: Demographics, Histology, Distribution and Clinical Significance: A Review of 15 Autopsy Cases." (Jesse Mostoller, Neel Hedge, Nick Taylor). "GATA3 Positive Malignant Spindle Cell Neoplasm Involving the Liver Diagnosed as Metastatic Sarcomatoid Chromophobe Renal Cell Carcinoma at Autopsy." (Rae Nusapan). "Long Term Outcome in a Case of Tetralogy of Fallot Surgically Treated with Palliative Shunts: Findings from an Adult Autopsy." (Dore Guptil, Heather Giguere). (11/2023)

Mark_FungCongratulations to Dr. Mark Fung, M.D., PhD., Professor Pathology and Laboratory Medicine, on receiving the 2023 College of American Pathologists (CAP) Lifetime Achievement Award. Dr. Fung is a nationally recognized expert in transfusion medicine. (10/2023) 

Congratulations to Jessica Crothers, M.D., Assistant Professor Pathology and Laboratory Medicine, on achieving the Notice of Special Interest Team Science award from NIAID for: "Effects of the gut microbiota on oral vaccine response in adults and children." (10/2023)

Nicole BouffardCongratulations to Nicole Bouffard on being awarded the "Scientific Research Staff Award" for 2023. This was presented to Nicole at the September 21, 2023, LCOM Research Excellence Award Ceremony. This is a great honor for Nicole and the Department of Pathology and recognizes her contributions and importance to the department and MIC. (10/2023)

Congratulations to Brian Cunniff, Ph.D., Assistant Professor Pathology and Laboratory Medicine, on being awarded a $1.6 million R01 grant by the National Institute of General Medical Sciences to study the role of mitochondrial trafficking in regulating cell migration, a key feature of metastatic tumors. (9/2023)

Congratulations to Yvonne Janssen-Heininger, Ph.D., Professor Pathology and Laboratory Medicine, on becoming a University of Vermont Cancer Center Program Co-Leader, Cancer Cell. (9/2023)

Congratulations to the following pathology members on receiving research support funds in April 2023. Recipients were: John Kennedy, M.D., $6520 for morphologic and immunohistochemical re-evaluation of renal cell carcinomas exhibiting papillary architecture, with emphasis on tumors demonstrating "type 2" morphology. Yvonne Janssen-Heininger, Ph.D., $15,000 for a joint initiative between RBP, UVM Cancer Center, and faculty in the Department of Chemistry. Megan Tarte $745 for Stem Cells, Cell Therapies, and Bioengineering in Lung Biology and Disease Conference. Albert van der Vliet, Ph.D., $14,400 for Redox processes in macrophage activation in IPF. (9/2023)

Congratulations to the following faculty members on their promotions: Vikas Anathy, Ph.D., to Professor with tenure, Bronwyn Bryant, M.D., to Associate Professor, John DeWitt, M.D., Ph.D., to Associate Professor, Sarah Nowak Ph.D., to Associate Professor, and Christi Wojewoda, M.D., to Professor. (6/2023)

Bei Zhang, M.D., M.S., Ph.D., MLS(ASCP), associate professor of pathology and laboratory medicine, did an educational scholarship session titled "Activate Students Learning Outside Classroom." at the 8th International meeting of the Association of Biochemistry Educators. Dr. Zhang also conducted two additional workshops with other ABE members titled "Linking Clinical Presentations to Their Biochemistry: A novel ABE Clinical-Biochemistry Curricular Treat Mapping Educational Tool.", and "Getting to Clerkship and Beyond: Crafting Biochemistry Learning Objectives that Connect and Integrate Basic Science Concepts with Clinical Application." (5/2023)

Congratulations to Dr. Maureen Harmon, M.D., associate professor of pathology and laboratory medicine, and Dr. Amer Abu Alfa, M.D., assistant professor of pathology and laboratory medicine for being recognized by medical students for their professionalism. Dr. Harmon was recognized for social responsibility and Dr. Abu Alfa was recognized for compassion. (5/2023)

Congratulations to Mary Cushman, Ph.D., M.Sc., professor of medicine and pathology and laboratory medicine, on being named a University Distinguished Professor of Medicine, Hematology/Oncology Division, and Pathology and Laboratory Medicine. (5/2023)

View the story Mammograms of a study by Sarah Nowak, Ph.D., assistant professor of pathology and laboratory medicine, and researchers at the UVM Cancer Center showing data that fewer women being screened for breast cancer. (4/2023)

vandervliet-habibovic420x280A new study by Albert van der Vliet, Ph.D., professor of pathology and laboratory medicine, and a team of University of Vermont (UVM) researchers is honing in on why people with asthma often have worse symptoms if they are obese. This new research demonstrates that the gene DUOX1 likely contributes to the connection between obesity and asthma.  The research was published ahead of print in the American Journal of Physiology-Lung Cellular and Molecular Physiology and was highlighted as an APSselect article for March 2023. Albert van der Vliet, Ph.D., was the senior author on the paper, along with department of pathology and laboratory medicine coauthors Aida Habibovic, lab research technician;Litiele Cruz, Ph.D., visiting scholar; Vikas Anathy, Ph.D., associate professor; University Distinguished Professor Yvonne Janssen-Heininger, Ph.D.; and additional team members and authors from UVM. Read the full LCOM News story LCOM News (4/2023)

Congratulations to Bronwyn Bryant, M.D., Assistant Professor of Pathology and Laboratory Medicine, for having your proposal, Consequential Validity of Entrustable Professional Activities in Pathology Residency Training selected to receive a Frymoyer Scholars Program project of $48,000 to be funded July 1, 2023 through June 30, 2025. (4/2023)

Congratulations to Martin Chang, M.D., Ph.D., on accepting the new role as Vice Chair for Faculty Affairs. (4/2023)

Congratulations to Joanna Conant, M.D., on becoming the new Pathology Student Fellowship Director starting July 1, 2023. (4/2023)

Congratulations to The Cunniff Lab, on receiving funding to support research focused on malignant mesothelioma. The funding was from The Butler Family Foundation Fund for Cancer Research at the University of Vermont Cancer Center. The Butler Fund was established by the Butler family in memory of two loved ones lost to mesothelioma. (03/2023)