Three ATS assemblies have joined forces to examine “the most interesting thing happening in the world of science as related to lung pathophysiology”—proteostasis, a mash-up of the words protein and homeostasis that refers to the second, and lesser-known, part of the protein life cycle.

Proteostasis is the most interesting topic in pathophysiology because it is in an emerging area in the understanding of age-related diseases such as COPD and fibrosis, says Karen Ridge, PhD, who organized the Tuesday session. An NHLBI workshop led the Assembly on Respiratory Cell and Molecular Biology, the Assembly on Allergy, Immunology, and Inflammation, and the Assembly on Respiratory Structure and Function to explore the topic.

Clinicians and researchers will be familiar with the first part of the proteostasis mash-up—protein synthesis, which is regulated by transcription, RNA stability, and translation, says Dr. Ridge, a professor of medicine and cell and molecular biology at Northwestern University.

“I don’t think many of the attendees will be familiar with the term proteostasis, which describes a universal protein folding, processing, trafficking, and degradation management program that dynamically sustains the functional properties of each protein in health and, most of the time, protects us from disease,” she says.

Cellular or environmental perturbations cause protein unfolding or misfolding that will push healthy cells toward disease if misfolded proteins cannot be repaired or degraded by adaptive responses within the proteostatic network. These response mechanisms are aimed at preserving proteostasis protection of the cell and include activation of the heat-shock response, antioxidant and redox signaling unfolded protein response, and the mitochondrial-specific UPR.

Clinicians and physician-scientists alike will benefit from the symposium, Dr. Ridge says. “Changes in protein folding—or aberrant, misfolding—can contribute to COPD, pulmonary fibrosis, cystic fibrosis, and a plethora of other diseases.”

The session will highlight the work of two leaders in the field: William E. Balch, PhD, professor of molecular medicine at The Scripps Research Institutes, La Jolla, California, and Michael F. Beers, MD, professor of medicine at the University of Pennsylvania School of Medicine. Dr. Balch will speak on the impact of malfolded proteins on lung pathophysiology, its progression, and application of proteostasis to precision medicine-based personalized management of lung health. Dr. Beers will discuss how aberrant cell quality control and stress responses are drivers of fibrotic lung disease and the impact that management of these proteostasis pathways could have in preserving lung function.

The four other speakers in the symposium will present talks on the regulation of heat shock proteins and their role in the proteostatic network.

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