Dr. Xiaopeng Li is an Associate Professor in the Department of Pediatrics and Human Development in the College of Human Medicine. His main research objective is to investigate the roles of the distal small airways in the pathogenesis of cystic fibrosis (CF) lung disease. CF is caused by defects in cystic fibrosis transmembrane conductance regulator (CFTR), an anion channel permeable to both chloride and bicarbonate. In CF patients, airway infection and inflammation are the main causes of CF morbidity and mortality. It is generally believed that the small airway abnormalities are involved in early CF lung disease pathogenesis. However, we have more knowledge of how the loss of CFTR function leads to host defense defects in large CF airways, the mechanism of how CF small airway is susceptible to infection and inflammation is not clear. We assume that the mechanism of the abnormalities in small CF airways are the same as large airways. This assumption may not correct as differences in epithelial morphology, cell types and gene expression profile, and lack of submucosal glands and continuous cartilages suggest that small airways are not the same as large airways. In fact, using the CF pig model, we established regional differences in CFTR expression, airway-surface liquid (ASL) pH, and bacterial killing in pig large vs. small airway epithelia. We will investigate the mechanisms underlying regional differences in regulation of ASL pH which determines host defense function. Moreover, we will investigate if selective modulation of ASL pH in the small airways will prevent or delay the development of CF lung disease.
Education & Training
Postdoctoral Research Associate, Department of Internal Medicine, Joseph Zabner Lab, University of Iowa, USA
Postdoctoral Research Associate, Department of Internal Medicine, Hal Chapman Lab, University of California San Francisco, USA
PhD, Physiology, Department of Physiology, Bruce Uhal Lab, Michigan State University, USA
MS, Medicine, Hunan Medical University, People's Republic of China
Gene Therapy Center of University of Iowa/ CF Gene Therapy Pilot Grant “Role of disrupted ASL pH regulation in small airways in CF lung disease pathogenesis”
Cystic Fibrosis Foundation/ CFF Research Grant LIX16G0 “Role of small airway epithelial cells in cystic fibrosis lung disease initiation”
Cystic Fibrosis Foundation Therapeutics/ Stem Cell Applications for CF Therapy LIX15XX0 “Evolving recombinant adeno-associated virus to target pig lung stem cells”
American Heart Association/ AHA Scientist Development Grant 14SDG18730009 “Cardiogenic pulmonary edema resolution with CFTR potentiator”
Cystic Fibrosis Foundation/ CFF Pilot Grant “Role of small airway epithelial cells in cystic fibrosis lung disease initiation”
Selected Peer-Reviewed Publications
Li X*, Tang XX, Vargas Buonfiglio LG, Comellas AP, Thornell IM, Ramachandran S, Karp PH, Taft PJ, Sheets K, Abou Alaiwa MH, Welsh MJ, Meyerholz DK, Stoltz DA, Zabner J. Electrolyte transport properties in distal small airways from cystic fibrosis pigs with implications for host defense. Am J Physiol Lung Cell Mol Physiol. 2016 Jan 22: ajplung.00422.2015. doi: 10.1152/ajplung.00422.2015. PMID: 26801568. (* corresponding author)
Li X*, Vargas Buonfiglio LG, Zabner J, Comellas AP. CFTR potentiation as a therapeutic strategy for pulmonary edema: a proof-of-concept experimental study in pigs. Crit Care Med. 2017 Dec; 45(12): e1240-e1246. PMID: 28953499 (* corresponding author).
Li X*, Rossen N, Steines B, Karp PH, Ernst SE, Adam RJ, Moninger TO, Zabner J. Integrin α6β4 identifies human distal lung epithelial progenitor cells with potential as a cell-based therapy for cystic fibrosis lung disease. PLoS One. 2013 Dec 12; 8(12): e83624. PMID: 24349537; PMCID: PMC3861522. (* corresponding author)
Li X, Comellas AP, Karp PH, Ernst SE, Moninger TO, Gansemer ND, Taft PJ, Pezzulo AA, Rector MV, Rossen N, Stoltz DA, McCray PB Jr, Welsh MJ, Zabner J. CFTR is required for maximal transepithelial liquid transport in pig alveolar epithelia. Am J Physiol Lung Cell Mol Physiol. 2012 Jul; 303(2): L152-60. PMID: 22637155; PMCID: PMC3404631.
Chapman HA, Li X*, Alexander JP, Brumwell A, Lorizio W, Tan K, Sonnenberg A, Wei Y, Vu TH. Integrin α6β4 identifies an adult distal lung epithelial population with regenerative potential in mice. J Clin Invest. 2011 Jul 1; 121(7):2855-62. PMID: 21701069; PMCID: PMC3223845. (* Co-first author)
Li X, Molina-Molina M, Abdul-Hafez A, Ramirez J, Serrano-Mollar A, Xaubet A, Uhal B: Extravascular sources of lung angiotensin peptides synthesis in idiopathic pulmonary fibrosis Am J Physiol Lung Cell Mol Physiol. 2006 Nov; 291(5): L887-95. PMID: 16844946.
Li X, Rayford H, Shu R, Zhuang J, Uhal BD. Essential role for cathepsin D in bleomycin-induced apoptosis of alveolar epithelial cells. Am J Physiol Lung Cell Mol Physiol. 2004 Jul; 287(1): L46-51. PMID: 14977632.
Li X, Rayford H, Uhal BD. Essential roles for angiotensin receptor AT1a in bleomycin-induced apoptosis and lung fibrosis in mice. Am J Pathol. 2003 Dec; 163(6): 2523-30. PMID: 14633624.
Awards & Honors
Scientist Development Grant, American Heart Association National Affiliate 2014
Outstanding Poster Award for "Plasminogen Activation & Extracullar Proteolysis", Gordon Research Conference, 2008
Postdoctoral Fellowship Award, American Physiological Society, 2005
Predoctoral Fellowship Award, American Heart Association Midwestern Affiliate, 2003