image: Assistant professors Archana Varadaraj (pictured at right) and Narendiran Rajasekaran of Northern Arizona University’s Department of Chemistry and Biochemistry were awarded a $469,034 grant by the NIH to investigate a potential treatment for IPF, building on their team’s previous findings involving the high-molecular weight adhesive glycoprotein fibronectin in renal and breast cancer research. view more
Credit: Northern Arizona University
Idiopathic Pulmonary Fibrosis (IPF) is a serious, irreversible disease that causes scar tissue to build up in the lung, making it hard to breathe and slowing oxygen flow into the bloodstream. The activation of various cytokines (proteins that control the growth and activity of other immune system cells and blood cells) during the process of fibrosis exacerbates disease progression and severity.
According to the National Institutes of Health (NIH), about 100,000 people in the United States have IPF, and approximately 30,000 to 40,000 new cases are found each year. Although there are drugs on the market that help patients breathe more easily, and some patients may receive lung transplants, there is no cure for IPF.
Assistant professors Archana Varadaraj and Narendiran Rajasekaran of Northern Arizona University’s Department of Chemistry and Biochemistry were awarded a $469,034 grant by the NIH to investigate a potential treatment for IPF, building on their team’s previous findings involving the high-molecular weight adhesive glycoprotein fibronectin in renal and breast cancer research.
As IPF progresses, the body produces a matrix of proteins, including fibronectin, that makes lung tissue more rigid, impacting lung function. Varadaraj, principal investigator on the project, hypothesizes that by targeting this matrix with a protein domain that is conserved among a family of immune suppressive proteins, the team will be able to show that matrix formation and fibrosis can be reversed—based on strong preliminary data from previous experimental and mouse studies, which showed a demonstrable reversal of the disease. The grant will enable the team to narrow down the precise mechanisms by which disease reversal occurs and to identify the immune modulators that contribute to this reversal.
“Like numerous disease states, IPF develops from the contribution of the microenvironment such as the extracellular matrix and immune milieu and defects within the cells that are intrinsic,” Varadaraj said. “Hopefully the NIH funding will allow us to identify the contribution of each of these factors with a goal of targeting it. Ultimately, we hope to provide therapeutic agents that can be used either on their own or in combination with existing therapies to reverse fibrosis and restore lung function.”
Rajasekaran, co-principal investigator on the project, who shares NAU’s Cancer Biochemistry and Immunology Lab with Varadaraj, focuses on elucidating the biochemical and immunological processes controlling cancer initiation and metastasis. He will characterize the role immune cells in fibrosis resolution in this project.
Assistant professor Megha Padi, director of the Bioinformatics Shared Resource (BISR) at The University of Arizona Cancer Center, specializes in computational genomics and will serve as collaborator on the project. Varadaraj and Rajasekaran will work with Padi to discover and validate new mechanisms triggered by the protein domain to better understand how fibronectin matrix degradation resolves the disease.
The research team will mentor undergraduate and graduate students to conduct experiments using immunocytochemistry and immunoblotting methods, analyze data and present their findings at national conferences.
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About Northern Arizona University
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