Scott A Boitano
Associate Research Scientist, Respiratory Sciences
Professor, BIO5 Institute
Professor, Cellular and Molecular Medicine
Professor, Physiological Sciences - GIDP
Professor, Physiology
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.


Boitano, S., Hoffman, J., Flynn, A. N., Asiedu, M. N., Tillu, D. V., Zhang, Z., Sherwood, C. L., Rivas, C. M., DeFea, K. A., Vagner, J., & Price, T. J. (2015). The novel PAR2 ligand C391 blocks multiple PAR2 signalling pathways in vitro and in vivo. British journal of pharmacology.

Proteinase-activated receptor-2 (PAR2) is a GPCR linked to diverse pathologies, including acute and chronic pain. PAR2 is one of the four PARs that are activated by proteolytic cleavage of the extracellular amino terminus, resulting in an exposed, tethered peptide agonist. Several peptide and peptidomimetic agonists, with high potency and efficacy, have been developed to probe the functions of PAR2, in vitro and in vivo. However, few similarly potent and effective antagonists have been described.

Hoffman, J., Flynn, A. N., Tillu, D. V., Zhang, Z., Patek, R., Price, T. J., Vagner, J., & Boitano, S. (2012). Lanthanide labeling of a potent protease activated receptor-2 agonist for time-resolved fluorescence analysis. Bioconjugate chemistry, 23(10), 2098-104.

Protease activated receptor-2 (PAR(2)) is one of four G-protein coupled receptors (GPCRs) that can be activated by exogenous or endogenous proteases, which cleave the extracellular amino-terminus to expose a tethered ligand and subsequent G-protein signaling. Alternatively, PAR(2) can be activated by peptide or peptidomimetic ligands derived from the sequence of the natural tethered ligand. Screening of novel ligands that directly bind to PAR(2) to agonize or antagonize the receptor has been hindered by the lack of a sensitive, high-throughput, affinity binding assay. In this report, we describe the synthesis and use of a modified PAR(2) peptidomimetic agonist, 2-furoyl-LIGRLO-(diethylenetriaminepentaacetic acid)-NH(2) (2-f-LIGRLO-dtpa), designed for lanthanide-based time-resolved fluorescence screening. We first demonstrate that 2-f-LIGRLO-dtpa is a potent and specific PAR(2) agonist across a full spectrum of in vitro assays. We then show that 2-f-LIGRLO-dtpa can be utilized in an affinity binding assay to evaluate the ligand-receptor interactions between known high potency peptidomimetic agonists (2-furoyl-LIGRLO-NH(2), 2-f-LIGRLO; 2-aminothiazol-4-yl-LIGRL-NH(2), 2-at-LIGRL; 6-aminonicotinyl-LIGRL-NH(2), 6-an-LIGRL) and PAR(2). A separate N-terminal peptidomimetic modification (3-indoleacetyl-LIGRL-NH(2), 3-ia-LIGRL) that does not activate PAR(2) signaling was used as a negative control. All three peptidomimetic agonists demonstrated sigmoidal competitive binding curves, with the more potent agonists (2-f-LIGRLO and 2-at-LIGRL) displaying increased competition. In contrast, the control peptide (3-ia-LIGRL) displayed limited competition for PAR(2) binding. In summary, we have developed a europium-containing PAR(2) agonist that can be used in a highly sensitive affinity binding assay to screen novel PAR(2) ligands in a high-throughput format. This ligand can serve as a critical tool in the screening and development of PAR(2) ligands.

Clark, J. A., Doelle, S. M., Halpern, M. D., Saunders, T. A., Holubec, H., Dvorak, K., Boitano, S. A., & Dvorak, B. (2006). Intestinal barrier failure during experimental necrotizing enterocolitis: protective effect of EGF treatment. American journal of physiology. Gastrointestinal and liver physiology, 291(5), G938-49.

Necrotizing enterocolitis (NEC) is the most common intestinal disease of premature infants. Although increased mucosal permeability and altered epithelial structure have been associated with many intestinal disorders, the role of intestinal barrier function in NEC pathogenesis is currently unknown. We investigated the structural and functional changes of the intestinal barrier in a rat model of NEC. In addition, the effect of EGF treatment on intestinal barrier function was evaluated. Premature rats were divided into three groups: dam fed (DF), formula fed (NEC), or fed with formula supplemented with 500 ng/ml EGF (NEC + EGF); all groups were exposed to asphyxia/cold stress to develop NEC. Intestinal permeability, goblet cell density, mucin production, and composition of tight junction (TJ) proteins were evaluated in the terminal ileum, the site of NEC injury, and compared with the proximal jejunum, which was unaffected by NEC. Animals with NEC had significantly increased intestinal paracellular permeability compared with DF pups. Ileal goblet cell morphology, mucin production, and TJ composition were altered in animals with NEC. EGF treatment significantly decreased intestinal paracellular permeability, increased goblet cell density and mucin production, and normalized expression of two major TJ proteins, occludin and claudin-3, in the ileum. In conclusion, experimental NEC is associated with disruption of the intestinal barrier. EGF treatment maintains intestinal integrity at the site of injury by accelerating goblet cell maturation and mucin production and normalizing expression of TJ proteins, leading to improved intestinal barrier function.

Burgess, J. L., Kurzius-Spencer, M., Poplin, G. S., Littau, S. R., Kopplin, M. J., Stürup, S., Boitano, S., & Clark Lantz, R. (2015). Environmental arsenic exposure, selenium and sputum alpha-1 antitrypsin. Journal of exposure science & environmental epidemiology, 24(2), 150-5.
BIO5 Collaborators
Scott A Boitano, Jefferey L Burgess, Clark Lantz

Exposure to arsenic in drinking water is associated with increased respiratory disease. Alpha-1 antitrypsin (AAT) protects the lung against tissue destruction. The objective of this study was to determine whether arsenic exposure is associated with changes in airway AAT concentration and whether this relationship is modified by selenium. A total of 55 subjects were evaluated in Ajo and Tucson, Arizona. Tap water and first morning void urine were analyzed for arsenic species, induced sputum for AAT and toenails for selenium and arsenic. Household tap-water arsenic, toenail arsenic and urinary inorganic arsenic and metabolites were significantly higher in Ajo (20.6±3.5 μg/l, 0.54±0.77 μg/g and 27.7±21.2 μg/l, respectively) than in Tucson (3.9±2.5 μg/l, 0.16±0.20 μg/g and 13.0±13.8 μg/l, respectively). In multivariable models, urinary monomethylarsonic acid (MMA) was negatively, and toenail selenium positively associated with sputum AAT (P=0.004 and P=0.002, respectively). In analyses stratified by town, these relationships remained significant only in Ajo, with the higher arsenic exposure. Reduction in AAT may be a means by which arsenic induces respiratory disease, and selenium may protect against this adverse effect.

Polley, D., Mihara, K., Ramachandran, R., Vliagoftis, H., Renaux, B., Saifeddine, M., Daines, M. O., Boitano, S., & Hollenberg, H. (2017). Cockroach allergen serine proteinases: Isolation, sequencing and signalling via proteinase-activated receptor-2. Clinical and Experimental Allergy, 47(7), 946-960. doi:10.1111/cea.12921

BACKGROUND: Allergy to the German cockroach (Blattella germanica) is a significant asthma risk factor for inner-city communities. Cockroach, like other allergens, contains trypsin-like enzyme activity that contributes to allergenicity and airway inflammation by activating proteinase-activated receptors (PARs). To date, the enzymes responsible for the proteolytic activity of German cockroach allergen have not been characterized. OBJECTIVES: We aimed to identify, isolate and characterize the trypsin-like proteinases in a German cockroach allergen extract used for clinical skin tests. For each enzyme, we sought to determine (1) its substrate and inhibitor enzyme kinetics (Km and IC50); (2) its amino acid sequence and (3) its ability to activate calcium signaling and/or ERK1/2 phosphorylation via PAR2. METHODS: Using a trypsin-specific activity-based probe, we detected three distinct enzymes that were isolated using ion-exchange chromatography. Each enzyme was sequenced by mass spectometery (deconvoluted with an expressed sequence tag library), evaluated kinetically for its substrate/inhibitor profile and assessed for its ability to activate PAR2 signaling. FINDINGS: Each of the three serine proteinase-activity-based probe-labelled enzymes isolated were biochemically distinct, with different enzyme kinetic profiles and primary amino acid sequences. The three enzymes showed a 57 to 71% sequence identity with a proteinase previously cloned from the American cockroach (Per a 10). Each enzyme was found to activate both Ca++ and MAPK signaling via PAR2. CONCLUSIONS AND RELEVANCE: We have identified three distinct allergen proteinases from the German cockroach that may play different roles for allergen-sensitization in vivo via PAR2 and may represent attractive therapeutic targets for asthma.