Dr. Kosuke Kato, PhD, is an assistant professor with the Division of Pulmonary, Allergy, Critical Care and Sleep Medicine in the Department of Medicine at the University of Arizona College of Medicine – Tucson. He also works in the lab of Louise Hecker, PhD, at the UA BIO5 Institute, whose research has focused on developing new, innovative therapies to treat indiopathic pulmonary fibrosis and other fibrotic diseases. Dr. Kato received his doctorate in medical and pharmaceutical sciences from Kumamoto University in Japan. He performed his post-doctoral training at Lovelace Respiratory Research Institute in Albuquerque, N.M., and at Temple University School of Medicine Lung Center in Philadelphia, under the mentorship of Kwang Chul Kim, PhD, a pioneer in the field of airway mucin biology, who also is now a UA Otolaryngology faculty member. Dr. Kato trained a number of research fellows and managed center projects, which resulted in several publications in peer-reviewed journals, including original research and review articles as well as a book chapter.
Dr. Kato’s research expertise is in understanding the mechanical, immunological and biological role of airway mucus in acute and chronic respiratory diseases. Airway mucus constitutes a thin layer of airway surface liquid that covers the luminal surface of the respiratory tract, which through a process known as mucociliary clearance provides a highly effective defense against pathogens, particles and toxic chemicals. Mucins make up a major part of airway mucus. The gel-forming mucins (MUC5AC and MUC5B) are responsible for the viscoelastic property of mucus and contribute to mucociliary clearance. Membrane-tethered mucins (MUC1, MUC4 and MUC16), expressing on the luminal surface of epithelium, serve as decoy receptor for bacterial pathogens through their extracellular domains and regulate intracellular signaling cascades through their cytoplasmic domains. However, the mechanisms underlying cellular and molecular properties of airway mucins and their regulation in respiratory diseases are not completely understood.
Dr. Kato’s ongoing research projects include:
- Pseudomonas aeruginosa respiratory infection research: P. aeruginosa is an opportunistic pathogen that can potentially cause infection in at risk hosts such as patients with COPD and cystic fibrosis. Understanding the pathogenesis of P. aeruginosa respiratory infection is critical to developing more effective therapeutic approaches. Dr. Kato and his colleagues identified membrane-tethered MUC1 mucin expressed in the cell surface of airway epithelial cells as an adhesion site for bacterial pathogen through its ectodomain and negatively regulates Toll-like receptors (TLRs) through its cytoplasmic domain. Dr. Kato published the first manuscript revealing that MUC1 mucin is expressed not only in airway epithelium but also in a subset of macrophage populations, where MUC1 mucin attenuates excess inflammatory responses.
- Interstitial lung diseases (ILD) research: MUC1 mucin is a biomarker widely used by the Japanese for close to two decades in the diagnosis and prognosis of ILDs. The goal of our research is to determine the contribution of functional MUC1 in the pathophysiology of ILD in order to develop a novel therapeutic approach for this disease.
- Chronic obstructive pulmonary disease (COPD) research: Cigarette smoking is the most common cause of COPD and accounts for more than 95% of cases in industrialized countries. COPD is predicted to become the third largest cause of death in the world by 2020. The goal of our research is to understand the role of MUC1 mucin in the pathophysiology of COPD. COPD exhibits characeristics of airway mucus hypersecretion that are associated with goblet cell hyperplasia and excessive mucus in the airway lumen. Mucus hypersecretion could cause airway obstruction, airflow limitation and impairment of gas exchange. With impaired mucociliary clearance, COPD patient with mucus hypersecretion become more prone to bacterial infection and exacerbation. Understanding the underlying molecular mechanisms involved in airway mucus hypersecretion is important to develop more effective therapeutic approaches for COPD.