Scott A Boitano

Scott A Boitano

Professor, Physiology
Professor, Cellular and Molecular Medicine
Professor, Physiological Sciences - GIDP
Associate Research Scientist, Respiratory Sciences
Professor, BIO5 Institute
Primary Department
Department Affiliations
(520) 626-2105

Research Interest

Dr. Scott Boitano Ph.D., is a Professor of Physiology, Cellular and Molecular Medicine, the BIO5 Institute and Associate Research Scientist of the Arizona Respiratory Center. Dr. Boitano received a B.S. in Plant Biology from University of California; Berkeley and a Ph.D. in Genetics & Cell Biology from Washington State University. Dr. Boitano’s primary research interest is in cell respiration. This encompasses the analysis and observation of cell physiology, cell-cell communications and cell-pathogen interactions. Dr. Boitano’s research pertains to the upper airway epithelium is an active cellular layer with ciliary movement to clear materials, the ability to secrete inflammatory effectors, and a biological barrier function that helps protect against pathogenic microorganisms, foreign insults and injury. Although much is known concerning the microbial genetics and microbial signaling of infection by Bordetella, relatively little is known about host cell pathology after exposure to Bordetella. Individuals have a primary tissue culture system that serves as an in vitro model of airway cell signaling and communication, and a battery of B. bronchiseptica strains, some of which are mutant in key factors shown to inhibit their ability to establish infection in animal models. His research goal is to define specific pathogen factors that alter host cell physiology to initiate or overcome host cell defense. The Boitano lab also analyzes the layers of the alveoli of the distal mammalian lung. Minimal information is known about this subject and Dr. Boitano believes that this model system for alveolar intercellular communication could expedite the formulating and testing of new medical treatments for dysfunctional alveolar cell physiology that underlies specific airway conditions following disease, insult and injury in the lung.


Sherwood, C. L., Daines, M. O., Price, T. J., Vagner, J., & Boitano, S. (2014). A highly potent agonist to protease-activated receptor-2 reveals apical activation of the airway epithelium resulting in Ca2+-regulated ion conductance. American journal of physiology. Cell physiology, 307(8), C718-26.

The airway epithelium provides a barrier that separates inhaled air and its various particulates from the underlying tissues. It provides key physiological functions in both sensing the environment and initiating appropriate innate immune defenses to protect the lung. Protease-activated receptor-2 (PAR2) is expressed both apically and basolaterally throughout the airway epithelium. One consequence of basolateral PAR2 activation is the rapid, Ca(2+)-dependent ion flux that favors secretion in the normally absorptive airway epithelium. However, roles for apically expressed PAR2 activation have not been demonstrated, in part due to the lack of specific, high-potency PAR2 ligands. In the present study, we used the newly developed PAR2 ligand 2at-LIGRLO(PEG3-Pam)-NH2 in combination with well-differentiated, primary cultured airway epithelial cells from wild-type and PAR2 (-/-) mice to examine the physiological role of PAR2 in the conducting airway after apical activation. Using digital imaging microscopy of intracellular Ca(2+) concentration changes, we verified ligand potency on PAR2 in primary cultured airway cells. Examination of airway epithelial tissue in an Ussing chamber showed that apical activation of PAR2 by 2at-LIGRLO(PEG3-Pam)-NH2 resulted in a transient decrease in transepithelial resistance that was due to increased apical ion efflux. We determined pharmacologically that this increase in ion conductance was through Ca(2+)-activated Cl(-) and large-conductance K(+) channels that were blocked with a Ca(2+)-activated Cl(-) channel inhibitor and clotrimazole, respectively. Stimulation of Cl(-) efflux via PAR2 activation at the airway epithelial surface can increase airway surface liquid that would aid in clearing the airway of noxious inhaled agents.

Isakson, B. E., Olsen, C. E., & Boitano, S. (2006). Laminin-332 alters connexin profile, dye coupling and intercellular Ca2+ waves in ciliated tracheal epithelial cells. Respiratory research, 7, 105.

Tracheal epithelial cells are anchored to a dynamic basement membrane that contains a variety of extracellular matrix proteins including collagens and laminins. During development, wound repair and disease of the airway epithelium, significant changes in extracellular matrix proteins may directly affect cell migration, differentiation and events mediated by intercellular communication. We hypothesized that alterations in cell matrix, specifically type I collagen and laminin alpha3beta3gamma2 (LM-332) proteins within the matrix, directly affect intercellular communication in ciliated rabbit tracheal epithelial cells (RTEC).

Lantz, R. C., Chau, B., & Boitano, S. A. (2016). Inhalation of arsenic-containing dusts during lung development alters pulmonary function in adult mice. Toxicological Sciences.
BIO5 Collaborators
Scott A Boitano, Clark Lantz
Tillu, D. V., Hassler, S. N., Burgos-Vega, C. C., Quinn, T. L., Sorge, R. E., Dussor, G., Boitano, S., Vagner, J., & Price, T. J. (2015). Protease activated receptor 2 (PAR2) activation is sufficient to induce the transition to a chronic pain state. Pain.

Protease Activated Receptor Type 2 (PAR2) is known to play an important role in inflammatory, visceral and cancer-evoked pain based on studies using PAR2 knockout (PAR2) mice. Here we have tested the hypothesis that specific activation of PAR2 is sufficient to induce a chronic pain state via extracellular signal-regulated kinase (ERK) signaling to protein synthesis machinery. We have further tested whether the maintenance of this chronic pain state involves a brain-derived neurotrophic factor (BDNF) / tropomyosin related kinase B (trkB) / atypical protein kinase C (aPKC) signaling axis. We observed that intraplantar injection of the novel, highly specific PAR2 agonist, 2-aminothiazol-4-yl-LIGRL-NH2 (2-at), evokes a long-lasting acute mechanical hypersensitivity (ED50 ∼ 12 pmoles), facial grimacing and causes robust hyperalgesic priming as revealed by a subsequent mechanical hypersensitivity and facial grimacing to prostaglandin E2 (PGE2) injection. The pro-mechanical hypersensitivity effect of 2-at is completely absent in PAR2 mice as is hyperalgesic priming. Intraplantar injection of the upstream ERK inhibitor, U0126 and the eukaryotic initiation factor (eIF) 4F complex inhibitor, 4EGI-1, prevented the development of acute mechanical hypersensitivity and hyperalgesic priming following 2-at injection. Systemic injection of the trkB antagonist ANA-12 likewise inhibited PAR2-mediated mechanical hypersensitivity, grimacing and hyperalgesic priming. Inhibition of aPKC (intrathecal delivery of ZIP) or trkB (systemic administration of ANA-12) after the resolution of 2-at-induced mechanical hypersensitivity reversed the maintenance of hyperalgesic priming. Hence, PAR2 activation is sufficient to induce neuronal plasticity leading to a chronic pain state, the maintenance of which is dependent on a BDNF/trkB/aPKC signaling axis.

Straub, A. C., Johnstone, S. R., Heberlein, K. R., Rizzo, M. J., Best, A. K., Boitano, S., & Isakson, B. E. (2010). Site-specific connexin phosphorylation is associated with reduced heterocellular communication between smooth muscle and endothelium. Journal of vascular research, 47(4), 277-86.

Myoendothelial junctions (MEJs) represent a specialized signaling domain between vascular smooth muscle cells (VSMC) and endothelial cells (EC). The functional consequences of phosphorylation state of the connexins (Cx) at the MEJ have not been explored.