Matthias A. Salathe, M.D.
Professor of Medicine
Description of Research
Dr. Salathe’s research focuses on signaling in the airway epithelium; particularly how signaling is affected by cigarette smoke and other irritants that lead to chronic bronchitis and possibly lung cancer. Dr. Salathe is involved in many basic, translational and clinical projects in this area of research. Most relevant to cancer research, Dr. Salathe, together with Dr. Schmid, are assessing how chronic inflammatory airway diseases, including smoking-induced chronic bronchitis, lead to damage of the airway epithelium with subsequent impairment of mucociliary clearance and development of squamous metaplasia. The epithelial damage is continuously repaired with the goal regenerating its regular structure. During repair, an initial phase of cell proliferation is followed by re-differentiation of epithelial cells, mechanisms regulated by reactivation of developmental signaling such as Wnt and the pathways stimulated by retinoic acid (RA). RA deprivation and cigarette smoke exposure-induced chronic bronchitis lead to squamous metaplasia and impaired ciliogenesis via altered expression of Wnt pathway elements, and in some cases leading to lung cancer. These outcomes can be improved by activation of PPAR gamma receptors. Research will investigate whether specific Wnt pathway elements are essential for ciliogenesis and prevention of squamous metaplasia and whether RA is an indispensable regulator of this process. In addition, we will examine whether the expression of Wnt pathway elements is altered in patients with smoking-related chronic bronchitis and lung cancer and whether this alteration leads to squamous metaplasia and impaired ciliogenesis. Finally, we will determine whether activation of nuclear receptors (e.g., PPAR gamma and vitamin D) prevents the development of squamous metaplasia and improves ciliogenesis by substituting for RA. Such approaches could also be used s cancer prevention strategies in high-risk individuals.
Dr. Salathe also began collaborating with Drs. Podack, Raez, and Rosenblatt, pursuing new strategies to increase the effectiveness of vaccine approaches to lung cancer.
- Novel aspects of airway epithelial signaling important for homeostasis the human airways (regulation of ciliary beating, ion fluxes, involvement of glycosaminoglycans, host defense mechanisms including bacterial host defense)
- Development of highly differentiated human airway epithelial cell cultures for use in research of human airway diseases and use of lentivirus manipulations of proteins in these cells to examine signaling, cell fate and differentiation signals
Selected Cancer-Related Publications
- Schmid A, Sutto Z, Schmid N, Novak L, Ivonnet P, Horvath G, Conner G, Fregien N, Salathe M. Decreased soluble adenylyl cyclase activity in cystic fibrosis is related to defective apical bicarbonate exchange and affects ciliary beat frequency regulation. J Biol Chem 285:29998-30007, 2010 Read more »
- Gattas MV, Forteza R, Fragoso MA, Fregien N, Salas P, Salathe M, Conner GE. Oxidative epithelial host defense is regulated by infectious and inflammatory stimuli. Free Radic Biol Med 47(10):1450-8, 2009 Read more »