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. 这些蛋白质的基因存在显著的遗传变异，导致个体对各种环境损害和传染病的易感性. 我们克隆并鉴定了人表面活性剂蛋白编码区遗传变异的结构和功能差异，以及人表面活性剂蛋白非编码区(5′-UTR和3′-UTR)在mRNA稳定性和蛋白表达中的调控作用. Furthermore, 我们首次产生了人源化转基因小鼠(表达人表面活性蛋白基因，不含小鼠表面活性蛋白基因) 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, 人表面活性剂蛋白基因变异的功能和调控差异可导致个体对肺部疾病和传染病的易感性, thus providing importantly molecular mechanisms for developing personalized medicine based on genomic profile of the individual

Recently, 主要研究方向为:(1)环境损伤(细菌、病毒病原体和环境颗粒物)暴露对表面活性剂蛋白功能障碍的影响 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, 我们正在开展一个项目，研究preRNA剪接机制和TP53基因多态性在肺癌发病中的作用.

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: http://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)轻度创伤性脑损伤通过调节肺泡巨噬细胞杀菌活性和M1极化减轻肺炎诱导的肺损伤. 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, 彭忠，石强(2021)抑制Notch活性促进急性胰腺炎后胰腺细胞角蛋白5阳性细胞向β细胞分化并改善葡萄糖稳态内分泌功能. 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)通过NF-κB/HIF-2α轴抑制，恢复软骨稳态，抑制软骨细胞凋亡，从而缓解骨关节炎的进展. Journal of Molecular Medicine. 98(10):1479-1491. Published online: 28 August 2020. http://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)人表面活性剂蛋白B变异对铜绿假单胞菌肺炎脓毒症遗传易感性的调控作用. 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)人SP-A1和SP-A2对肺炎克雷伯菌和臭氧暴露的BAL蛋白质组和信号通路的差异影响. 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)表面活性蛋白D通过抑制NLRP3炎性小体激活，减轻重症急性胰腺炎诱导的炎症和损伤. 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)肺和肾表面活性物质蛋白D通过调节肺肾串扰和调节肾细胞凋亡来保护肺炎引起的急性肾损伤, 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, 刘庆平(2018)表面活性剂蛋白D通过抑制p38 MAPK信号通路减缓一氧化氮刺激的大鼠软骨细胞凋亡. 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, 张士康(2017)同步胃腺癌与胃肠道间质瘤的临床病理及分子特征. 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)表面活性蛋白- d (SP-D)基因多态性和血清水平对中国人群急性肾损伤易感性和预后的预测作用. 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)高气道压力和动态应变对非均质急性肺损伤模型呼吸机肺损伤的作用. 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)人SP-B基因变异对细菌性肺炎肺损伤的差异易感性及化学修饰姜黄素的影响. 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)富氢盐水通过抑制炎症和细胞凋亡减轻急性坏死性胰腺炎的急性肝损伤, 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)先天免疫分子表面活性剂蛋白D通过调节细胞凋亡和nf - kb介导的炎症减轻败血症诱导的急性胰腺损伤. 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和Floros J(2013)表面活性剂蛋白B (SFTPB)内含子4 CA-repeat-rich区域内的基序对mRNA剪接的影响存在差异. 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)人类SP-A1和SP-A2基因5'-UTR剪接变异体介导的翻译效率和mRNA稳定性差异. 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)人类表面活性剂蛋白B SNP1580位点C和T等位基因n -链糖基化的差异:疾病含义. 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.