Dr. Qing Lu, D.V.M., Ph.D. is Associate Professor of Medicine at Alpert Medical School of Brown University and Research Biologist at Providence VA Medical Center. Dr. Lu’s research focuses on lung endothelial biology and innate immunity in cigarette smoke-associated pulmonary diseases, particularly acute respiratory distress syndrome (ARDS), emphysema and pulmonary artery hypertension (PAH). Dr. Lu’s research is currently funded by NIH Ro1. She was also the Principal Investigator (PI) of the project 1 of the CPVB COBRE grant and the PI of several other projects funded by the American Thoracic Society (ATS)/Pulmonary Hypertension Association, the American Lung Association, the Francis Family Foundation, and the Rhode Island Foundation. Dr. Lu has published 50 manuscripts/review articles/ book chapters.
Dr. Lu has served as ad hoc member of NIH study sections (RIBT and LCMI), Department of Defense PRMRP Scientific Peer Review Panels, American Heart Association Peer Review Panels, ATS Peer Review Panels, and several international funding agencies. She is an Academic Editor of journal PLOS ONE and an ad hoc reviewer for many prominent journals. She is currently a member of the Pulmonary Circulation (PC) Planning Committee of ATS and the President of Chinese-America Lung Association. Dr. Lu has served as a member of the Medical Faculty Executive Committee of Brown University in the last 3 years and the Chair of the Institutional Animal Care and Use Committee (IACUC) and the Associate Chair of the Subcommittee for Research Safety (SRS) at Providence VA Medical Center in the last 6 years. As a mentor for various training programs, Dr. Lu has mentored students ranging from undergraduates, graduate students and medical students to pulmonary fellows and post-doctoral fellows. Currently, she serves as a mentor for Dr. Hongwei Yao, a junior investigator of Phase II of the CPVB COBRE. Dr. Lu has taught several courses, including Physiology and Principle of Biology.
Plasma adenosine is increased in patients with sepsis-induced acute lung injury (ALI) and the levels of plasma adenosine correlate with poor survival. Human and mice with adenosine deaminase (ADA) deficiency display progressive lung injury and respiratory distress, suggesting that sustained elevated adenosine is detrimental to the lungs. Our preliminary data demonstrate that prolonged cigarette smoke (CS) exposure increases lung adenosine and exacerbates ALI in mice. We also show that sustained adenosine exposure causes lung endothelial cell (EC) barrier dysfunction via nucleotide transporter (ENT1/2)-dependent, oxidative stress-mediated p38 activation and mitochondrial dysfunction. Thus, we hypothesize that sustained elevated adenosine contributes to CS-primed ALI via ENT1/2-mediated mitochondrial dysfunction and resultant increase permeability pulmonary edema. The long-range goal is to develop novel therapeutic approaches to prevent and treat lung diseases associated with sustained increased adenosine and CS exposure. Specific Aim 1 will determine whether ENT1/2 and mitochondrial oxidative stress mediate increased permeability pulmonary edema in ADA deficient mice and CS-primed ALI mice. Specific Aim 2 will identify the mechanism of deleterious effects of sustained elevated adenosine on mitochondrial function and barrier function of cultured lung EC. These studies will elucidate a novel pathway of adenosine effects mediated by intracellular uptake of adenosine. Inhibition of ENT1/2-facilitated adenosine transport and/or mitochondrial dysfunction may likely provide significant and greatly needed new approaches to treat lung diseases associated with sustained elevated adenosine and CS exposure.
Two manuscripts related to the Specific Aim 2 have been published on this project. Other proposed studies are ongoing.
Alfred Ayala, PhD
Professor of Surgery
Rhode Island Hospital
Ocean State Research Institute
Providence VA Medical Center
830 Chalkstone Avenue
Providence RI 02908
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Research reported in this website was supported by the National Institute of General Medical Science of the National Institutes of Health under grant number P20GM103652.