Guirong Wang, PhD

EDUCATION

RESEARCH ABSTRACT

Human surfactant is a complex of phospholipids and surfactant-associated proteins, which is essential for life. Surfactant proteins consist of four proteins (A, B, C, D) i.e. SP-A, SP-B, SP-C and SP-D. SP-A and SP-D are members of C-type lectin family and play critical roles of innate immunity and host defense against various microorganisms and other environmental insults; SP-B and SP-C are hydrophobic proteins essential for the life due to lowering surface tension of lung alveoli as well as host defense. The genes of these proteins exist significant genetic variations that cause individual susceptibility to various environmental insults and infectious diseases. We have cloned and identified structural and functional differences of human surfactant protein genetic variants of coding region and the regulatory roles of the non-coding regions (5’-UTR and 3’-UTR) of human surfactant proteins in the mRNA stability and protein expression. Furthermore, we are at the first time generated humanized transgenic mice (which express human surfactant protein gene but without mouse surfactant protein gene) as in vivo tool and then study their function and molecular mechanisms of surfactant proteins, and genetic susceptibility of individuals in response to environmental insults (ozone, ambient particulate matter) exposure and infectious conditions. The findings from our studies demonstrate structural, functional and regulatory differences of human surfactant protein genetic variants that can cause individual susceptibility to pulmonary diseases and infectious diseases, thus providing importantly molecular mechanisms for developing personalized medicine based on genomic profile of the individual

Recently, we focus on the following studies: (1) effects of ambient environmental insults (bacterial and viral pathogens and ambient particulate matter) exposure on surfactant protein dysfunction in vitro and in vivo; (2) the genetic susceptibility of SP-A, SP-B, SP-D to infection and acute lung injury using our humanized transgenic mice; (3) the roles of innate immunity of surfactant collectins (SP-A and SP-D) in the extrapulmonary organs, including kidney, intestine, middle ear, eye and pancreas, in several different disease models; (4) mucosal innate immunity of human SP-A and SP-D genetic variants against SARS-CoV-2 infectivity. In addition, we are developing a project to study of preRNA splicing mechanisms and the role of TP53 gene polymorphisms in the pathogenesis of lung cancer.

Active Research Support

Publications (selected from total 107 peer-reviewed research papers)

1. Abdel-Razek O, Audlin J, Poe SD, and Wang G (2022) Surfactant Proteins and Innate Immunity of Otitis Media (Review). Innate Immunity (In press). PMID: 36069032. OnlineFirst: https://journals.sagepub.com/doi/10.1177/17534259221123309
2. Xiong W, Perna A, Jacob BI, Lundgren RB and Wang G (2022) The enhancer-binding protein MifR, an essential regulator of α-ketoglutarate transport, is required for full virulence of Pseudomonas aeruginosa PAO1 in a mouse model of pneumonia. Infection and Immunity (In press). Publish Ahead of Print PMID: 36125307. doi: 10.1128/iai.00136-22.
3. Ruan F, Chen J, Yang J and Wang G (2022) Mild Traumatic Brain Injury Attenuates pneumonia-induced Lung Injury by modulations of alveolar macrophage bactericidal activity and M1 Polarization. Shock (In press). Publish Ahead of Print DOI: 10.1097/SHK.0000000000001989
4. Zhang X, Tao J, Yu J, Hu N, Zhang X, Wang G, Feng J, Xiong X, Li M, Chai D, Li H, Rong Y, Tang Z, Wang W, Peng Z and Shi Q (2021) Inhibition of Notch activity promotes pancreatic cytokeratin 5-positive cell differentiation to beta cells and improves glucose homeostasis endocrine function following acute pancreatitis. Cell Death and Disease. 12:867. PMID: 34556631; PMCID: PMC8460737; DOI: 10.1038/s41419-021-04160-2.
5. Abdel-Razek O, Liu T, Chen X, Wang Q, Vanga G, Wang G (2021) Role of Surfactant Protein D in Experimental Otitis Media. Journal of Innate Immunity. 13(4):197-210 doi: 10.1159/000513605. Open access. PMID:33556949
6. Zhou Y, Ming J, Deng M, Li Y, He B, Wang G, Liu S. (2020) A chemically modified curcumin (CMC2.24) alleviates osteoarthritis progression by restoring cartilage homeostasis and inhibiting chondrocyte apoptosis via NF-κB/HIF-2α axis suppression. Journal of Molecular Medicine. 98(10):1479-1491. Published online: 28 August 2020. https://doi.org/10.1007/s00109-020-01972-1.
7. Shi C, Wang X, Wang L, Meng Q, Guo D, Chen L, Dai M, Wang G, Cooney R, Luo J. (2020) A nanotrap improves survival in severe sepsis by attenuating hyperinflammation. Nature Communications 2020 Jul 7;11(1):3384. PubMed PMID: 32636379; PubMed Central PMCID: PMC7341815.
8. Yang F, Zhang J, Yang Y, Ruan F, Chen X, Guo J, Abdel-Razek O, Zuo YY, Wang G. (2020) Regulatory Roles of Human Surfactant Protein B Variants on Genetic Susceptibility to Pseudomonas Aeruginosa Pneumonia-Induced Sepsis. Shock. 54(4):507-519. PMID:31851120 doi: 10.1097/SHK.0000000000001494. Open Access
   This article has been chosen by the Editor-in-Chief to be of particular interest.
9. Abdel-Razek O, Ni L, Yang F, Wang G (2019) Innate Immunity of Surfactant Protein A in an Experimental Otitis Media. Innate Immunity. 25(7):391-400. doi: 10.1177/1753425919866006. PMCID: PMC6900641. Open Access
10. Wang G (as the corresponding author), Umstead TM, Hu S, Mikerov AN, Phelps DS, Floros J. (2019) Differential Effects of Human SP-A1 and SP-A2 on the BAL Proteome and Signaling Pathways in Response to Klebsiella pneumoniae and Ozone Exposure. Front Immunol. 10:561. doi: 10.3389/fimmu.2019.00561. PubMed PMID: 30972061; PMCID: PMC6443908. Open Access
11. Yu J, Ni L, Zhang XY, Zhang J, Abdel-Razek O, Wang G (2019) Surfactant protein D alleviates severe acute pancreatitis-induced inflammation and injury by suppressing NLRP3 inflammasome activation. Shock. 51(5):557-568. PubMed PMID: 30124598; PubMed Central PMCID: PMC6393216.
12. Guo L, Meng M, Wei Y, Lin F, Jiang Y, Cui X, Wang G, Wang C, Guo X. (2019) Protective Effects of Live Combined B. subtilis and E. faecium in Polymicrobial Sepsis Through Modulating Activation and Transformation of Macrophages and Mast Cells. Front. Pharmacol. 9:1506. doi: 10.3389/fphar.2018.01506. PubMed PMID: 30719003; PubMed Central PMCID: PMC6348999.
13. Du J, Abdel-Razek O, Shi Q, Hu F, Ding G, Cooney NR, Wang G (2018) Both pulmonary and renal surfactant protein D protects against pneumonia-induced acute kidney injury through modulating lung-kidney crosstalk and regulating renal apoptosis, inflammation and NF-κB activation. Scientific Reports. 8:15393. DOI:10.1038/s41598-018-33828-7 PMCID:PMC6193952. Open Access
14. Jia Q, Guo L, Fang Y, Wang G (2018) Efficient Privacy-preserving machine learning for hierarchical distributed system. Transactions on network Science and Engineering-IEEE. 14(8):2327-4679.
15. Shi Q, Hong YP, Zhang XY, Tao J, Wang CY, Zhao L, Mei FC, You YD, Xia H, Xiong XC, Wang G, Wang WX (2018) β cells can be generated from cytokeratin 5-positive cells after cerulein-induced pancreatitis in adult mice. Biochem Biophys Res Commun. 496(1):114-119. doi: 10.1016/j.bbrc.2018.01.008. PMID: 29307825. Open Access
16. Zhou Y, Ming JH, Li YM, Deng M, He B, Zhou JL, Wang G, Liu SQ (2018) Surfactant Protein D attenuates nitric oxide-stimulated apoptosis in rat chondrocyte by suppressing p38 MAPK signaling. Biochem Biophys Res Commun, 495(1):526-532. doi.org/10.1016/j.bbrc.2017.10.170. Open Access
17. Luo JM, Cao FL, Meng C, Lin LJ, Ma SQ, Peng SH, Gao HL, Javidiparsijani S, Wang G, Zhang ML, Xin JG, Wang YC, Zhang SK ( 2017) Clinicopathological and molecular characteristics of synchronous gastric adenocarcinoma and gastrointestinal stromal tumors. Scientific Reports. 7(1):12890. PMCID: PMC5635104. Open Access
18. Zhang L, Meng Q, Yepuri N, Wang G, Xi X, Cooney RN. (2017) Surfactant Proteins-A and -D attenuate LPS-induced Apoptosis in Primary Intestinal Epithelial Cells (IECs). Shock. 49(1):90-98. doi: 10.1097/SHK.0000000000000919. PMID 28591009.
19. Liu J, Li G, Li L, Liu Z, Zhou Q, Wang G, Chen D. (2017) Surfactant protein-D (SP-D) gene polymorphisms and serum level as predictors of susceptibility and prognosis of acute kidney injury in the Chinese population. BMC Nephrol. 2017 Feb 17;18(1):67. doi: 10.1186/s12882-017-0485-x. PMID:28212617. Open Access
20. Zhang XY, Shi Q, Wang CT, Wang G (2017) Differential susceptibility of mouse strains on pancreatic injury and regeneration in cerulein-induced pancreatitis. Int J of Clin Exp Pathol. 10(9):9934-9944. Open Access
21. Jain SV, Kollisch-Singule M, Satalin J, Searles Q, Dombert L, Abdel-Razek O, Yepuri N, Leonard A, Gruessner A, Andrews P, Fazal F, Meng Q, Wang G, Gatto LA, Habashi NM, Nieman GF. (2017) The role of high airway pressure and dynamic strain on ventilator-induced lung injury in a heterogeneous acute lung injury model. Intensive Care Med Exp. 5(1):25. doi: 10.1186/s40635-017-0138-1. PMID: 28497420.
22. Kollish-Singule M, Jain SV, Satalin J, Andrews P, Searles Q, Liu ZY, Zhou Y, Wang G, Meier AH, Gatto LA, Nieman GF, Habashi NM (2017) Limiting ventilator-associated lung injury in a preterm porcine neonatal model. Journal of Pediatric Surgery. 52(1):50-55. PMID: 27837992.
23. Ge L, Liu X, Chen R, Xu Y, Zuo YY, Cooney RN, Wang G: (2016) Differential susceptibility of transgenic mice expressing human surfactant protein B genetic variants to Pseudomonas aeruginosa induced pneumonia. Biochem. Biophys. Res. Commun. 469(2):171-5. PMID: 26620227; PMCID: PMC4698049. Open Access
24. Hu F, Ding G, Gatto L, Hawgood S, Poulain F, Cooney R, Wang G (2016) Innate immunity of surfactant protein A and D in urinary tract infections. Innate Immunity 22(1)9-20. PMID:26511057. PMCID: PMC4679646. Open Access
25. Xu Y, Ge L, Abdel-Razek O, Jain S, Liu Z, Hong Y, Nieman G, Johnson F, Golub LM, Cooney RN, Wang G. (2016) Differential susceptibility of human SP-B genetic variants on lung injury caused by bacterial pneumonia and the effect of chemically modified curcumin. Shock 45(4):375-84. PMID: 26863117; PMCID: PMC4698049.
26. Shi Q, Chen C, Deng WH, Wang P, Zuo T, Zhao L, Yu J, Zhao KL, Mei FC, Li C, Wang G, and Wang WX. (2016) Hydrogen-rich saline attenuates acute hepatic injury in acute necrotizing pancreatitis by inhibiting inflammation and apoptosis, involving JNK and p38 mitogen-activated protein kinase-dependent reactive oxygen species. Pancreas 45(10)1424-1431.
27. Liu J, Abdel-Razek O, Liu Z, Hu F, Zhou Q, Cooney RN, Wang G (2015) Role of surfactant proteins A and D in sepsis-induced acute kidney injury. Shock 43:31-38. PMCID: PMC4269566.
28. Liu Z, Shi Q, Liu J, Abdel-Razek O, Xu Y, Cooney RN, Wang G (2015) Innate immune molecule surfactant protein D attenuates sepsis-induced acute pancreatic injury through modulating apoptosis and NF-kB-mediated inflammation. Scientific Reports 5:17798 | DOI: 10.1038/srep17798. PMCID: PMC4669466. Open Access
29. Zhang Z, Abdel-Razek O, Hawgood S, Wang G (2015) Protective role of surfactant protein D in ocular Staphylococcus aureus infection. PLOS ONE 10(9):e0138597. PMCID: PMC4580580. Open Access
30. Yang WJ, Ni L, Silveyra P, Wang G, Noutsios TG, Singh A, DiAngelo S, Sanusi O, Raval M and Floros J (2013) Motifs within the CA-repeat-rich region of surfactant protein B (SFTPB) intron 4 differentially affect mRNA splicing. Journal of Molecular Biochemistry. 2:41-56.
31. Roy S, Habashi N, Sadowitz B, Andrews P, Ge L, Wang G, Roy P, Ghosh A, Kuhn M, Satalin J, Gatto AL, Lin L, Dean AD, Vodovotz Y, Nieman G. (2013) Early airway pressure release ventilation prevents ARDS - A novel preventive approach to lung injury. Shock, 39(1):28-38.
32. Wang Y, Voelker D, Lugogo N, Wang G, Floros J, Ingram JL, Chu HW, Church TD, Fertel D, Wright JR, and Kraft M (2011) Surfactant Protein-A is Defective in Abrogating Inflammation in asthma. Am J Physiol -- Lung Cell Mol Physiol. 301:L598-L606.
33. Mikerov AN, Hu S, Durrani F, Gan X, Wang G, Umstead TM, Phelps DS, Floros J. (2012) Impact of sex and ozone exposure on the course of pneumonia in wild type and SP-A (-/-) mice. Microb Pathog. 52(4):239-249. PMCID: PMC3608432.
34. Mikerov AN, Cooper TK, Wang G, Hu S, Umstead TM, Phelps DS, Floros J. (2011) Histopathologic evaluation of lung and extrapulmonary tissues show sex differences in Klebsiella pneumonia -infected mice under different exposure conditions. Int J Physiol Pathophysiol Pharmacol 3(3):176-190. PMCID: PMC3175744.
35. Wang G, Guo XX, DiAngelo S, Thomas NJ, Floros J. (2010) Humanized SFTPA1 and SFTPA2 transgenic mice reveal functional divergence of SP-A1 and SP-A2: Formation of tubular myelin in vivo requires both gene products. J. Biol. Chem.
36. Wang G, Guo X, Silveyra P, Kimball SR, Floros J. (2009) Cap-independent translation of human SP-A 5'-UTR variants, A double -loop structure and cis-element contribution. Am J Physiol -- Lung Cell Mol Physiol. 296:L635-L647.
37. Wang G, Myers C, Mikerov A, Floros J. (2007) Effect of Cys85 on biochemical properties and biological function of human SP-A variants. Biochemistry. 46:8425-8435.
38. Wang G, Taneva S, Keough KMW, Floros J. (2007) Differential effects of human SP-A1 and SP-A2 variants on phospholipid monolayers containing surfactant protein B. Biochim Biophys Acta. 1768:2060-2069.
39. Wang G, Guo X, Floros J. (2005) Differences in the translation efficiency and mRNA stability mediated by 5'-UTR splice variants of human SP-A1 and SP-A2 genes. Am J Physiol -- Lung Cell Mol. Physiol. 289:L497-L508.
40. Wang G, Bates-Kenney SR, Tao JQ, Phelps DS, Floros J. (2004) Differences in biochemical properties and in biological function between human SP-A1 and SP-A2 variants, and the impact of ozone-induced oxidation. Biochemistry 2004, 43:4227:4239.
41. Wang G, Guo X and Floros J. (2003) Human SP-A 3'-UTR variants mediate differential gene expression in basal levels and in response to dexamethasone. Am J Physiol -- Lung Cell Mol Physiol. 284:L738-L748.
42. Wang G, Christensen N, Wigdahl B, Guttentag S Floros J. (2003) Differences in N-linked glycosylation between the C and T alleles at the SNP1580 of the human surfactant protein B: Disease implication. Biochem. J. 369(1):179-184.
43. Wang G, Umstead TM, Phelps DS, Al-Mondhiry H, Floros J (2002). The effect of ozone exposure on the ability of human surfactant A variants to stimulate cytokine production. Environmental Health Perspective. 110:79-84. PMCID: PMC1240696.
44. Wang G, Phelps DS, Umstead TM, Floros J (2000). Human SP-A protein variants derived from one or both genes stimulate TNF-a production in the THP-1 cell line. Am. J. Physiol.--Lung Cell Mol. Physiol. 278:L946-L954.