Jennifer A. Aguiar's research while affiliated with University of Waterloo and other places
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Publications (25)
Rationale
Despite its increasingly widespread use, little is known about the impact of cannabis smoking on the response to viral infections like influenza A virus (IAV). Many assume that cannabis smoking will disrupt antiviral responses in a manner similar to cigarette smoking, however, since cannabinoids exhibit anti-inflammatory effects, it sugge...
Introduction
Over 300 million people in the world live with asthma, resulting in 500,000 annual global deaths with future increases expected. It is estimated that around 50–80% of asthma exacerbations are due to viral infections. Currently, a combination of long-acting beta agonists (LABA) for bronchodilation and glucocorticoids (GCS) to control lu...
The angiotensin-converting enzyme 2 (ACE2) protein has been highly studied as a key catalytic regulator of the renin-angiotensin system (RAS), involved in fluid homeostasis and blood pressure modulation. In addition to its important physiological role as a broadly-expressed membrane-bound protein, ACE2 serves as a cell-surface receptor for some vir...
NK cells are central to anti-tumor immunity and recently showed efficacy for treating hematologic malignancies. However, their dysfunction in the hostile tumor microenvironment remains a pivotal barrier for cancer immunotherapies against solid tumors. Using cancer patient samples and proteomics, we found that human NK cell dysfunction in the tumor...
Accessible in vitro models recapitulating the human airway that are amenable to study whole cannabis smoke exposure are needed for immunological and toxicological studies that inform public health policy and recreational cannabis use. In the present study, we developed and validated a novel three-dimensional (3D)-printed in vitro exposure system (I...
Introduction
Over 300 million people in the world live with asthma, resulting in 500,000 annual global deaths with future increases expected. It is estimated that around 50-80% of asthma exacerbations are due to viral infections. Currently, a combination of long-acting beta agonists (LABA) for bronchodilation and glucocorticoids (GCS) to control lu...
Accessible in vitro models recapitulating the human airway that are amenable to study whole cannabis smoke exposure are needed for immunological and toxicological studies that inform public health policy and recreational cannabis use. In the present study, we developed and validated a novel 3D printed In Vitro Exposure System (IVES) that can be dir...
Cannabis smoking is the dominant route of delivery, with the airway epithelium functioning as the site of first contact. The endocannabinoid system is responsible for mediating the physiological effects of inhaled phytocannabinoids. The expression of the endocannabinoid system in the airway epithelium and contribution to normal physiological respon...
Background: The airway epithelium represents a critical component of the human lung that helps orchestrate defenses against respiratory tract viral infections, which are responsible for more than 2.5 million deaths/year globally. Innate immune activities of the airway epithelium rely on Toll-like receptors (TLRs), nucleotide binding and leucine-ric...
In December 2019, SARS-CoV-2 emerged causing the COVID-19 pandemic. SARS-CoV, the agent responsible for the 2003 SARS outbreak, utilises ACE2 and TMPRSS2 host molecules for viral entry. ACE2 and TMPRSS2 have recently been implicated in SARS-CoV-2 viral infection. Additional host molecules including ADAM17, cathepsin L, CD147, and GRP78 may also fun...
Two highly pathogenic human coronaviruses that cause severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) have evolved proteins that can inhibit host antiviral responses, likely contributing to disease progression and high case-fatality rates. SARS-CoV-2 emerged in December 2019 resulting in a global pandemic. Recent...
In December 2019, SARS-CoV-2 emerged causing the COVID-19 pandemic. SARS-CoV, the agent responsible for the 2003 SARS outbreak, utilizes ACE2 and TMPRSS2 host molecules for viral entry. ACE2 and TMPRSS2 have recently been implicated in SARS-CoV-2 viral infection. Additional host molecules including ADAM17, cathepsin L, CD147, and GRP78 may also fun...
Recreational and medicinal cannabis consumption in the past 12 months has been reported in 1/5 th of Canadians, with greater use in males relative to females. Cannabis smoking is the dominant route of delivery in consumers, with the airway epithelium functioning as the site of first contact for inhaled phytocannabinoids. The endocannabinoid system...
Background: The airway epithelium represents a critical component of the human lung that helps orchestrate defences against respiratory tract viral infections, which are responsible for more than 2.5 million deaths/year globally. Innate immune activities of the airway epithelium rely Toll-like receptors (TLRs), nucleotide binding and leucine-rich-r...
LABA/GC intervention in airway epithelial cells exposed to cannabis smoke reduces levels of pro-inflammatory (CXCL8) and antiviral (CXCL10) mediators, while transcriptomic signatures of neutrophil-mediated immunity and oxidative stress remain elevated http://bit.ly/2qiSQhH.
Globally, many jurisdictions are legalizing or decriminalizing cannabis, creating a potential public health issue that would benefit from experimental evidence to inform policy, government regulations, and user practices. Tobacco smoke exposure science has created a body of knowledge that demonstrates the conclusive negative impacts on respiratory...
ABC transporters are conserved in prokaryotes and eukaryotes, with humans expressing 48 transporters divided into 7 classes (ABCA, ABCB, ABCC, ABCD, ABDE, ABCF, and ABCG). Throughout the human body, ABC transporters regulate cAMP levels, chloride secretion, lipid transport, and anti-oxidant responses. We used a bioinformatic approach complemented w...
Global recreational cannabis use is a potentially important public health issue that would benefit from experimental evidence to inform policy, regulations, and individual user practices. Comparative analyses between cannabis and tobacco smoke, the latter long reported to have negative impacts on respiratory health, may help provide context and pro...
Rationale
The respiratory mucosa coordinates responses to infections, allergens, and exposures to air pollution. A relatively unexplored aspect of the respiratory mucosa are the expression and function of ATP Binding Cassette (ABC) transporters. ABC transporters are conserved in prokaryotes and eukaryotes, with humans expressing 48 transporters div...
Citations
... In recent years the interaction of mitochondria and lysosomes via membrane contact sites has been established (18). During immune responses, adaptations in metabolic flux help to sustain the elevated metabolic needs (7). Mitochondria and lysosomes are highly dynamic and constantly adapt to nutrient availability and receptor input (18,44). ...
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... Primary cells can be directly isolated from disease-specific lung tissue or healthy donors and can be expanded using standard cell culture methods. For example, our group isolates primary human bronchial epithelial cells from consented subjects undergoing a routine clinical procedure using a bronchial brushing (Dabaghi et al., 2021a;Chandiramohan et al., 2021) as well as primary human lung fibroblasts from lung tissues taken during resection (Dabaghi et al., 2021b). We have demonstrated that these primary cells can be expanded in regular tissue culture plates without losing functionality. ...
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... In particular, CB1 receptors are also expressed in pre-synaptic sympathetic nerve terminals innervating the cardiovascular systems [36]. Additionally, the respiratory system is controlled by the peripheral activation of CB1 and CB2 receptors [37] expressed in airway epithelial cells [38], bronchi, lung tissue, respiratory endothelium [37], and axon terminals of airways nerves [39]. ...
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... Statistical analyses. The statistical analyses of the processed microarray data were performed following the same methodology as described in our previous study 14 . Determination of statistically significant differential gene expression was performed using empirical Bayes method via the eBayes function from limma R package. ...
... SARS-CoV-2 virus enters host cells via the ACE2 receptor [20], [3]. ACE2 receptor is a type I transmembrane amino-peptidase found on cell surfaces of the gut, heart, lungs, and many other organs,and also found in solution in blood plasma and urine [25], [3]. The COVID-19 viral envelope's "spike" (S) protein binds to ACE2 receptors on nasopharyngeal mucosa and alveolar pneumocytes [20], [21], [51]. ...
... Interferon-related adaptations in bats include, e.g. constitutive and highly inducible expression, and expanded and divergent ranges of interferon-induced genes [18]. More generally, arms races of host interferon systems with viral anti-interferon tactics, in bats and other mammals, represent some of most diverse and complex molecular-conflictual interactions yet described, that lead to diverse outcomes in both bats and viruses that are expected to be specific to each host-virus interaction [19][20][21]. ...
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... Under homeostatic condition GRP78 remains bound to ATF6, IRE1, and PERK in the endoplasmic reticulum [36]. Increased GRP78 levels have been reported in COVID-19 patients [47,48], suggesting that GRP78 is liberate from its receptors, and translocates to the cell membrane. In fact, GRP78 directly interacts with SARS-CoV-2 S protein [36]. ...
... Both CB1 and CB2 receptors are expressed by eosinophils, monocytes and monocyte-derived macrophages [99,105]. CB1, CB2 and TRPV1 have been identified in situ and in vitro at the protein level in airway epithelial cells; however, the impact of these findings on the biology of respiratory inflammations remains unclear [106]. ...
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... A proportion of available smoke exposure research, primarily with tobacco, has been established through submerged monolayer culture designs in which smoke extract has been used to expose cells [32][33][34]. Our group has recently applied these methods to Calu-3 cells with cannabis smoke extract exposure and observed an induction of a proinflammatory cytokine response and suppression of antiviral cytokines [35,36]. Smoke extract exposures do not entirely reflect whole smoke exposure as the latter generates heat and water-insoluble hydrocarbon combustion products [21,[37][38][39]. ...
... The presence of extensive Placental ALP staining in the bronchiolar and alveolar lumina and in the contents of these lumina in the areas with high Placental ALP positivity demonstrated that some of the Placental ALP synthesized by the lung parenchyma was secreted into the bronchioloalveolar fluid. According to several publications, cigarette smokers have significantly higher levels of respiratory epithelial permeability (33,34). As a result, smokers may have higher blood levels of Placental ALP activity as a result of increased bronchioloalveolar liquid leaking into the pulmonary capillaries. ...
