Teal Hallstrand

Associate Professor
Division of Pulmonary and Critical Care Medicine


Faculty Web Page

Authored articles (PubMed)

Last Updated:  October 6, 2014

Research Focus

My laboratory studies the pathogenesis of asthma through translational human studies as well as in vitro models using primary human cells and selected in vivo models. A major focus is on the regulation of a group of inflammatory lipid mediators called eicosanoids (e.g. leukotrienes and prostaglandins). The increased production of these lipid mediators plays a central role in the pathogenesis of exercise-induced bronchoconstriction (EIB), and is also strongly implicated in other aspects of asthma, especially acute asthma exacerbations triggered by allergen and viral infection. We are particularly interested in understanding how the airway epithelium regulates the production of these inflammatory mediators by interacting with inflammatory cells such as mast cells and eosinophils that reside in close contact with the airway epithelium. Recent genome wide studies have identified several epithelial genes that may serve as primary regulators of the immune response leading to asthma. We have recently assembled a multi-faceted team of investigators with a common interest in epithelial biology located in the Pacific Northwest. This group of investigators called the Pacific Northwest Epithelial Biology Consortium (PNEC) includes researchers from the Center for Lung Biology (CLB), Benaroya Research Institute (BRI), Seattle Children’s Hospital, Oregon Health and Science University (OHSU) and University of British Columbia (UBC). My lab also has strong ongoing collaborations with Dr. William Henderson and Dr. Michael Gelb (Gelb Lab) focusing on the biology of lipid mediator formation. It is my hope that this research will lead to a better understanding of the biology of asthma and the development of new therapies for asthma.


Hallstrand Lab 2011 Nisha Chacko (Study Coordinator), Ying Lai, PhD (Post-doctoral Fellow), Teal Hallstrand MD, MPH (PI), John Vandree, MD (Researcher), and Jessica Plampin (Research Scientist Assistant).

Function of Secreted PLA2 Group X in Airway Pathophysiology
Several years ago, we began to investigate the inflammatory basis of exercise-induced bronchoconstriction (EIB), a hallmark feature of asthma that reflects indirect airway hyperresponsiveness (AHR). We found that patients with this distinctive phenotype have epithelial injury and high levels of cysteinyl leukotrienes (CysLT)s and other pro-inflammatory eicosanoids (Click Here) and that the release of these eicosanoids plays an essential role in the pathogenesis of EIB (Click Here). Work on the regulation of eicosanoid formation led us to identify secreted phospholipase A2 group X (sPLA2-X) that regulates the first rate-limiting step in eicosanoid formation (Click Here). We have now shown that sPLA2-X is the predominant sPLA2 in the airways of patients with asthma (Click Here) and have demonstrated that sPLA2-X is increased in asthma, is expressed primarily in the epithelium and serves as a key regulator of eicosanoid formation in epithelial cells (Click Here). We have also developed several model systems to understand the function of sPLA2-X in the epithelium including an in vitro model using well-differentiated primary airway epithelial cells from patients with and without asthma and murine model systems with selective deficiency of epithelial-derived sPLA2-X. We have shown that sPLA2-X acts of human eosinophils to initiate CysLT synthesis (see below) and are working on a study to demonstrate that epithelial-derived sPLA2-X activates eosinophils in close association with the epithelium.

Regulation of Leukotriene Synthesis by Eosinophils
Eosinophils are major source of CysLTs, and activation of these cells in the airways is strongly implicated in asthma. We recently demonstrated that exogenous sPLA2-X acts on human eosinophils to initiate CysLT formation by a mechanism that involves the generation of lysophospholipids enriched in arachidonic acid, and the activation of cytosolic PLA2a (cPLA2a) through p38 and JNK (Click Here). Although it has generally been accepted that cPLA2a is the major PLA2 residing within eosinophils, we have recently found that human eosinophils express sPLA2-X, that the sPLA2-X protein resides in the secretory compartment, including the granules (Figure A), and based on selective inhibitor studies, sPLA2-X plays a significant role in endogenous CysLT synthesis (Figure B). We have now demonstrated that priming of eosinophils by inflammatory stimuli increases LT formation through an increase in sPLA2-X (manuscript in revision). Regarding the relevance of eosinophil activation to human asthma, a recent collaboration with Dr. Richard Zangar from Pacific Northwest National Laboratory (PNNL) demonstrates that halotyrosine-modified proteins by eosinophils are strongly associated with airway hyperresponsiveness (Click Here).


Figure – Immunostaining for endogenous sPLA2-X in human eosinophils (A). Function of sPLA2-X in fMLP mediated eicosanoid synthesis based on inhibition of sPLA2-X with a highly selective sPLA2-X inhibitor (0929, B).

Intraepithelial Mast Cell Phenotype and Function
We demonstrated several years ago that mast cell degranulation is an important feature of the pathogenesis of EIB (Click Here). Because the susceptibility to EIB varies widely among subjects with asthma, we conducted a genome-wide expression study of airway cells and found that two mast cell genes, b-Tryptase and carboxypeptidase A3 (CPA3), are among the most strongly overexpressed in patients with EIB (Click Here). We have now demonstrated using epithelial brushings that mast cells with this unique phenotype of high Tryptase and CPA3 expression but low Chymase expression are increased in subjects with EIB, but not in other subjects with asthma suggesting that the intraepithelial mast cell phenotype is critical to the pathogenesis of EIB. We have now demonstrated using design-based stereology that the density of intra-epithelial mast cells is uniquely elevated in the group of subjects with EIB relative to asthmatics who have direct airway hyperresponsiveness but not EIB (Click Here). These findings indicate that mast cell infiltration of the airways is a defining feature of indirect airway hyperresponsiveness. 

Regulation and Function of Epithelial-derived IL-33
Recent genome wide association studies have strongly implicated IL-33 and the ST2 receptor in the pathogenesis of asthma. IL-33 can induce the development of AHR in murine models in the absence of the Th2 cytokine IL-4 and in the absence of T and B cell development. Mast cells and CD34+ progenitor cells represent a major target for IL-33 signaling. We are examining the hypothesis that sensitization and challenge in the absence of adjuvant induces airway inflammation and AHR in a mast cell dependent manner and that mast cells play a key role in the primary immune response (See Figure). We are establishing mast cell dependent models using ovalbumin without adjuvant, house dust mite and cockroach allergen, and complementing these studies with studies using human cord blood-derived mast cells. We are working in collaboration with other investigators through the PNEC on the specific role of epithelial IL-33 in murine models, the regulation of IL-33 by human epithelial cells and the genetics of IL-33 and ST2 expression.


Figure – Disease model of epithelial-derived IL-33 as a key initiator of the immune response to allergen such as house dust mite (HDM) or infection.


Relevant Publications

Hallstrand TS, Moody MW, Wurfel MM, Schwartz LB, Henderson WR, Jr., Aitken ML. Inflammatory basis of Exercise-induced bronchoconstriction. Am J Resp Crit Care Med 2005;172:679-686.

Hallstrand TS, Fischer ME, Wurfel MM, Afari N, Buchwald D, Goldberg J. Genetic Pleiotropy between Asthma and Obesity in a Community-based Sample of Twins. J Allergy Clin Immunol 2005;116:1235-41.

Hallstrand TS, Chi EY, Singer AG, Gelb MH, Henderson Jr WR. Secreted phospholipase A2 group X overexpression in asthma and bronchial hyperresponsiveness. Am J Respir Crit Care Med. 2007 176:1072-8. Epub 2007 Sep 27.

Jian-Qing H, Hallstrand TS, Knight D, Chan-Yeung M, Sandford A, Tripp B, Zamar D, Bossé Y, Kozyrskyj AL, James A, Laprise C, Daley D. A Thymic Stromal Lymphopoietin Gene Variant Is Associated with Asthma and Airway Hyperresponsiveness. J Allergy Clin Immunol. 2009 124: 222-9. Epub 2009 Jun 21.

Hallstrand TS, Wurfel MM, Lai Y, Ni Z, Gelb MH, Altemeier WA, Beyer RP, Aitken ML, Henderson WR Jr. Transglutaminase 2, a novel regulator of eicosanoid production in asthma revealed by genome-wide expression profiling of distinct asthma phenotypes. PLoS One. 2010 5: e8583.

Kicic A, Hallstrand TS, Sutanto EN, Stevens PT, Kobor MS, Taplin C, Pare PD, Beyer RP, Stick SM, Knight DM. Decreased fibronectin production significantly contributes to dysregulated repair of the asthmatic epithelium. Am J Respir Crit Care Med. 2010 181: 889-98. Epub 2010 Jan 28.

Lai Y, Oslund RC, Bollinger RC, Henderson WR, Jr., Santana L, Gelb MH, Hallstrand TS. Eosinophil cysteinyl leukotriene synthesis mediated by exogenous secreted phospholipase A2 group X. J Biol Chem. 2010 285:41491-500. Epub 2010 Oct 25.

Hallstrand TS, Lai Y, Ni Z, Oslund RC, Henderson WR, Jr., Gelb MH, Wenzel SE. Relationship between airway levels of secreted phospholipase A2 groups IIA and X and asthma severity. Clin Exp Allergy. 2011 41:801-10. Epub 2011 Jan 24.

Gharib SA, Nguyen EV, Lai Y, Plampin JD, Goodlett DR, Hallstrand TS. Induced sputum proteome in healthy subjects and asthmatic patients. J Allergy Clin Immunol. 2011 128:1176-1184.e6. Epub 2011 Sep 8.

Hallstrand TS, Lai Y, Altemeier WA, Appel CL, Johnson B, Frevert CW, Hudkins KL, Bollinger JG, Woodruff PG, Hyde DM, et al. Regulation and function of epithelial secreted phospholipase A2 group X in asthma. Am J Respir Crit Care Med 2013;188:42-50.

Lai Y, Altemeier WA, Vandree J, Piliponsky AM, Johnson B, Appel CL, Frevert CW, Hyde DM, Ziegler SF, Smith DE, Henderson WR, Jr., Gelb MH, Hallstrand TS. Increased density of intraepithelial mast cells in patients with exercise-induced bronchoconstriction regulated through epithelially derived thymic stromal lymphopoietin and IL-33. J Allergy Clin Immunol. 2014 133:1448-55.

Warner SM, Hackett TL, Shaheen F, Hallstrand TS, Kicic A, Stick SM, Knight DA. Transcription Factor p63 Regulates Key Genes and Wound Repair in Human Airway Epithelial Basal Cells. Am J Respir Cell Mol Biol 2013;49:978-988.


Active Funding

Funding Source

Project Title


Funding Dates

R01 HL089215

Secretory Phospholipase A2s in Airway Pathophysiology


04/2008 - 07/2018

NIH/NHLBI R21 HL111845

Function of secreted PLA2 group X in eosinophil biology


08/2012 - 05/2015

Current Mentees



Project & Funding

Luke Ogden


Function of secreted PLA2 in allergic inflammation


Past Mentees



Current title


Rachel Blazevic



Western Washington University

Pelle Arthur



University of Washington

Ying Lai


Research Scientist

University of Washington

Kathryn Hooper


Molecular Cellular Biology Grad Student

University of Washington

John Vandree


Clinical Practice


Rob Oslund


Post Doctoral Fellow


Chris Carlsten


Assistant Professor of Medicine

University of British Columbia

Jason S. Debley


Assistant Professor of Pediatrics

Seattle Children's Hospital

Kevin Sonn


Medical Student


Mahtab Fakhari


Medical Student

University of Kansas

Michael Compher


Air and Radiation Division Member


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