RESEARCH PROGRAMS AND AFFILIATIONS
Innate immunology; host defense; inflammatory regulation; Surfactant Protein expression, regulation and function; humanized transgenic mice; Bacterial and SARS-CoV-2 induced pneumonia and sepsis; acute lung injury and ARDS; lung stem cell and differentiation; PM2.5 induced pulmonary disease
ASSOCIATIONS / MEMBERSHIPS
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 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 studies: (1) effects of ambient environmental insults (bacterial pathogens and ambient particulate matter) exposure on surfactant protein dysfunction in vitro and lung injury in vivo; (2) the genetic susceptibility of human SP-A, SP-B, SP-D to infection and acute lung injury using our humanized transgenic mice; (3) the role of innate immunity of surfactant collectins (SP-A and SP-D) expressed in the extrapulmonary organs, including kidney, intestine, middle ear, eye and pancreas, in different disease models. 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
|NIH R01 HL136706||Wang, G. (PI)||04/1/2017 - 03/31/2023|
|NSF 16-601; 1722630||Wang, G. (PI)||10/1/2017 - 09/31/2022|
National Science Foundation
|NIH R01 GM130941||Luo, J. (PI)||09/01/2018-08/31/2023|
|Michael Connolly Endowment Fund||Wang, G. (PI)||06/1/2019 - 05/30/2022|
Upstate Cancer Research foundation
Publications (selected from total 107 peer-reviewed research papers)
1. 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. doi: 10.1097/SHK.0000000000001494. [Epub ahead of print]. Open Access
2. 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
3. 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
4. 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.
5. 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.
6. 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
7. 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.
8. 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
9. 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
10. 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
11. 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.
12. 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
13. 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
14. 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.
15. Li Y, Wang Y, Li Y, Li T, Mao H, Talbot R, Nie X, Wu C, Zhao Y, Hou C, Wang G, Zhou J, Qie G (2017) Characteristics and potential sources of atmospheric particulate mercury in Jinan, China. Sci Total Environ 574:1424-1431. Doi:10.1016/jscitotenv.2016.08.069.
16. 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.
17. 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
18. 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
19. 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.
20. Tseng LF, Wang J, Baker RM, Wang G, Mather PT, Henderson JH. (2016) Osteogenic Capacity of Human Adipose-Derived Stem Cells is Preserved Following Triggering of Shape Memory Scaffolds. Tissue Engineering, Part A. 22(15-16):1026-35.
21. 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.
22. 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.
23. 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
24. 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
25. 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.
26. 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.
27. 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.
28. 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.
29. 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.
30. 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.
31. 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.
32. 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.
33. 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.
34. 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.
35. 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.
36. 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.
37. 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.
38. 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.
39. 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.