Circadian-coupled Cellular and Lung Function in COPD
The major goals of this translational T1 proposal is to elucidate the role of peripheral circadian periodicity genes/proteins-CLOCK, BMAL1 and Period2 in regulating lung cellular, molecular and physiological functions in pathogenesis of COPD, and deficiency or posttranslational modifications of circadian proteins lead to loss of efficacy of steroids and β2-agonists in patients with COPD and during its exacerbations, and strategic chronotherapeutic manipulation of circadian proteins.
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Comparative Toxicology of Electronic Cigarettes with Flavorings
Electronic cigarettes (E-cigs) with different flavors represent a significant and increasing proportion of tobacco consumption in the United States and globally in youth/adult population. We are studying the aerosol constituents and cellular toxicity of E-cigs with nicotine and flavorings. The identification of established and potential harmful chemicals/constituents, and development of measurable comparative toxicity data based on oxidative stress, DNA damage and inflammation that result from exposure to E-cigs vapor with different flavorings are studied.
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Exosomes in Environmental Tobacco Smoke-induced Lung Cellular Senescence and Inflammation
Environmental tobacco smoke (ETS) or “secondhand smoke” exposure leads to stress-induced adverse outcomes including cellular senescence and toxicological effects on the lungs associated with systemic response/injury and inflammation in airway and other organ disorders. Exosomes/microparticles play an important role in maintaining normal cellular homeostasis via intercellular communication.
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Flavoring Inhalation Toxicology and Health Effects
Flavors increasingly drive the use of emerging tobacco and non-tobacco products. Many tobacco flavoring ingredients labeled ‘Generally Recognized as Safe (GRAS)’ were intended for foods but have not been evaluated for inhalation toxicity and human health effects. Flavors appear to play an important role in attracting users to these emerging tobacco products. Data are needed to understand consumer perceptions and use of flavored tobacco products, as well as the toxicity and health effects of such products.
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Mechanisms of Cigarette Smoke-induced Lung Cellular Senescence
The major goal of this proposal is to understand the mechanisms of cigarette smoke-induced cellular senescence and inflammation in p16-HDAC2 Stress-induced Premature Senescence in the pathogenesis of COPD.
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Mechanism of Mitochondrial Dysfunction By Inhaled Toxicants
Cigarette smoke (CS), the most important etiological risk factor for the development of COPD/emphysema, causes lung injurious and damaging responses. These effects include mitochondrial dysfunction and defective mitophagy (removal of damaged mitochondria from a cell prior to cell death).
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Nicotine Emissions, Toxicity, and Behavior by Electronic Cigarettes
This project looks at how the components and design features of electronic cigarettes vary among different manufacturers and how consumer behaviors affect emissions. Actual compensatory behaviors are not being used in this R21, making it distinct from the existing application. The project also looks at toxic effect and addictive response mouse model. This is a collaborative project with Dr. Risa Robinson and Dr. Todd Pagano (Rochester Institute of Technology, Rochester, NY).
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Role of Sirtuin in Regulation of Cigarette Smoke-induced Lung Inflammation and Injury
The major goal of this proposal is to understand the role of Sirtuin1 in lung premature aging (apoptosis/senescence), emphysema and inflammation in response to cigarette smoke and in patients with COPD. The proposal will identify key intracellular signaling events in the SIRT1 pathway and will allow us to identify therapeutic targets for CS-mediated abnormal lung inflammation and airway injury in pathogenesis of COPD. These studies have high translational potential as SIRT1 is implicated in control of aging, senescence and inflammation.
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Topography, Constituents, and Toxicity of Waterpipe/Hookah Flavored and Non-Flavored Tobacco Smoke
The popularity of waterpipe or hookah smoking as a behavioral/recreational/social activity is increasing in western countries. Little regulatory science is available to inform the Food and Drug Administration (FDA) on waterpipe tobacco health effects. Appropriate regulatory policy for waterpipe tobacco is currently hindered by the lack of data describing realistic use of these products and the resulting health impacts based on topography, constituents, and toxicology research.
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