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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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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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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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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