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Hongkuan Fan

Title
InstitutionMedical University of South Carolina
DepartmentPathology and Laboratory Medicine
AddressP.O. Box MSC 908
CRI 610
173 Ashley Ave.
Phone843-792-2978
ORCID ORCID Icon0000-0002-9441-9405 Additional info
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    Collapse Biography 
    Collapse education and training
    Jilin University, ChinaPh.D07/2001Biochemistry
    Jilin University, ChinaB.S.07/1996Biochemistry

    Collapse Overview 
    Collapse studies/trials
    Collapse overview
    Septic shock with multiple organ failure is the leading cause of death in non-coronary intensive care units and remains a major health problem in the US. Despite improvements in overall ICU care, efforts to discover targeted therapies for sepsis have been disappointing to date. Endothelial cell (EC) dysfunction, manifested by increases in vascular permeability, is an important hallmark of septic shock and plays a critical role in the pathogenesis of multi-organ failure. The long-term goal of our research is to identify novel treatment strategies to maintain endothelial barrier function in sepsis.

    1. Endothelial progenitor cells (EPC)s are bone marrow-derived endothelial precursor cells, which play critical roles in endothelial regeneration and repair. Circulating EPCs recently have been associated with sepsis. Specifically, EPCs from humans with sepsis demonstrate alterations in function and EPC proliferation is inversely related to organ dysfunction when compared to EPCs from healthy controls. The overall objective for this project is to identify the mechanisms by which EPCs modulate endothelial barrier dysfunction in sepsis. We are interested in therapeutic potential of EPC exosomes containing miRNAs.

    2. Pericytes (PC) maintain endothelial barrier function and represent a potential therapeutic target in sepsis. However, the processes that govern pericyte viability and their role in barrier function in sepsis have not yet been fully elucidated. The overall objective for this porject is to identify the determinants of pericyte viability in sepsis and the mechanisms by which pericytes maintain endothelial barrier function.
    Collapse keywords
    Vascular, Inflammation

    Collapse Research 
    Collapse research activities and funding
    R01GM113995     (FAN, HONGKUAN)Apr 1, 2015 - Mar 31, 2021
    NIH
    The Beneficial Effects of Endothelial Progenitor Cells in the Vascular Dysfunction of Sepsis
    Role: Principal Investigator

    R01GM130653     (FAN, HONGKUAN)Sep 21, 2018 - Aug 31, 2022
    NIH
    The Role of Pericytes in the Vascular Dysfunction of Sepsis
    Role: Principal Investigator

    R41AI157378     (FAN, HONGKUAN)Feb 5, 2021 - Jan 31, 2022
    NIH
    Use novel natural compound Sparstolonin B to treat bacterial sepsis
    Role: Principal Investigator

    Collapse Bibliographic 
    Collapse selected publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
    List All   |   Timeline
    1. Li P, Wu Y, Goodwin AJ, Halushka PV, Wilson CL, Schnapp LM, Fan H. Generation of a new immortalized human lung pericyte cell line: a promising tool for human lung pericyte studies. Lab Invest. 2021 May; 101(5):625-635. PMID: 33446892.
      View in: PubMed
    2. Mu X, Fan H, Wang P, Li Y, Domenico K, Li Q, Wang X, Essandoh K, Chen J, Peng T, Fan GC. Sectm1a Facilitates Protection against Inflammation-Induced Organ Damage through Promoting TRM Self-Renewal. Mol Ther. 2021 03 03; 29(3):1294-1311. PMID: 33279722.
      View in: PubMed
    3. Wang X, Lennard Richard M, Li P, Henry B, Schutt S, Yu XZ, Fan H, Zhang W, Gilkeson G, Zhang XK. Expression of GM-CSF Is Regulated by Fli-1 Transcription Factor, a Potential Drug Target. J Immunol. 2021 01 01; 206(1):59-66. PMID: 33268481.
      View in: PubMed
    4. Wu Y, Li P, Goodwin AJ, Cook JA, Halushka PV, Zingarelli B, Fan H. miR-145a Regulation of Pericyte Dysfunction in a Murine Model of Sepsis. J Infect Dis. 2020 08 17; 222(6):1037-1045. PMID: 32285112.
      View in: PubMed
    5. Goodwin AJ, Li P, Halushka PV, Cook JA, Sumal AS, Fan H. Circulating miRNA 887 is differentially expressed in ARDS and modulates endothelial function. Am J Physiol Lung Cell Mol Physiol. 2020 06 01; 318(6):L1261-L1269. PMID: 32321279.
      View in: PubMed
    6. Li P, Zhao R, Fan K, Iwanowycz S, Fan H, Li Z, Liu B. Regulation of dendritic cell function improves survival in experimental sepsis through immune chaperone. Innate Immun. 2019 05; 25(4):235-243. PMID: 31018807.
      View in: PubMed
    7. Fan H, Goodwin AJ. What's New in Shock, March 2019? Shock. 2019 03; 51(3):269-272. PMID: 30475330.
      View in: PubMed
    8. Zhou Y, Li P, Goodwin AJ, Cook JA, Halushka PV, Chang E, Zingarelli B, Fan H. Exosomes from endothelial progenitor cells improve outcomes of the lipopolysaccharide-induced acute lung injury. Crit Care. 2019 02 13; 23(1):44. PMID: 30760290.
      View in: PubMed
    9. Li P, Goodwin AJ, Cook JA, Halushka PV, Zhang XK, Fan H. Fli-1 transcription factor regulates the expression of caspase-1 in lung pericytes. Mol Immunol. 2019 04; 108:1-7. PMID: 30739075.
      View in: PubMed
    10. Jones Buie JN, Zhou Y, Goodwin AJ, Cook JA, Vournakis J, Demcheva M, Broome AM, Dixit S, Halushka PV, Fan H. Application of Deacetylated Poly-N-Acetyl Glucosamine Nanoparticles for the Delivery of miR-126 for the Treatment of Cecal Ligation and Puncture-Induced Sepsis. Inflammation. 2019 Feb; 42(1):170-184. PMID: 30244405.
      View in: PubMed
    11. Li P, Zhou Y, Goodwin AJ, Cook JA, Halushka PV, Zhang XK, Wilson CL, Schnapp LM, Zingarelli B, Fan H. Fli-1 Governs Pericyte Dysfunction in a Murine Model of Sepsis. J Infect Dis. 2018 11 05; 218(12):1995-2005. PMID: 30053030.
      View in: PubMed
    12. Zhou Y, Li P, Goodwin AJ, Cook JA, Halushka PV, Chang E, Fan H. Exosomes from Endothelial Progenitor Cells Improve the Outcome of a Murine Model of Sepsis. Mol Ther. 2018 05 02; 26(5):1375-1384. PMID: 29599080.
      View in: PubMed
    13. Jones Buie JN, Goodwin AJ, Cook JA, Halushka PV, Fan H. The role of miRNAs in cardiovascular disease risk factors. Atherosclerosis. 2016 11; 254:271-281. PMID: 27693002.
      View in: PubMed
    14. Guo C, Goodwin A, Buie JNJ, Cook J, Halushka P, Argraves K, Zingarelli B, Zhang X, Wang L, Fan H. A Stromal Cell-Derived Factor 1a Analogue Improves Endothelial Cell Function in Lipopolysaccharide-Induced Acute Respiratory Distress Syndrome. Mol Med. 2016 Sep; 22:115-123. PMID: 27031787.
      View in: PubMed
    15. Goodwin AJ, Guo C, Cook JA, Wolf B, Halushka PV, Fan H. Plasma levels of microRNA are altered with the development of shock in human sepsis: an observational study. Crit Care. 2015 Dec 18; 19:440. PMID: 26683209.
      View in: PubMed
    16. Li P, Guo Y, Bledsoe G, Yang ZR, Fan H, Chao L, Chao J. Kallistatin treatment attenuates lethality and organ injury in mouse models of established sepsis. Crit Care. 2015 May 01; 19:200. PMID: 25930108.
      View in: PubMed
    17. Guan S, Guo C, Zingarelli B, Wang L, Halushka PV, Cook JA, Fan H. Combined treatment with a CXCL12 analogue and antibiotics improves survival and neutrophil recruitment and function in murine sepsis. Immunology. 2014 Sep 08. PMID: 25201453.
      View in: PubMed
    18. Fan H, Goodwin AJ, Chang E, Zingarelli B, Borg K, Guan S, Halushka PV, Cook JA. Endothelial progenitor cells and a stromal cell-derived factor-1a analogue synergistically improve survival in sepsis. Am J Respir Crit Care Med. 2014 Jun 15; 189(12):1509-19. PMID: 24707934.
      View in: PubMed
    19. Li P, Bledsoe G, Yang ZR, Fan H, Chao L, Chao J. Human kallistatin administration reduces organ injury and improves survival in a mouse model of polymicrobial sepsis. Immunology. 2014 Jun; 142(2):216-26. PMID: 24467264.
      View in: PubMed
    20. Fan H. ß-Arrestins 1 and 2 are critical regulators of inflammation. Innate Immun. 2014 Jul; 20(5):451-60. PMID: 24029143.
      View in: PubMed
    21. Li P, Neubig RR, Zingarelli B, Borg K, Halushka PV, Cook JA, Fan H. Toll-like receptor-induced inflammatory cytokines are suppressed by gain of function or overexpression of Ga(i2) protein. Inflammation. 2012 Oct; 35(5):1611-7. PMID: 22581266.
      View in: PubMed
    22. Fan H, Wong D, Ashton SH, Borg KT, Halushka PV, Cook JA. Beneficial effect of a CXCR4 agonist in murine models of systemic inflammation. Inflammation. 2012 Feb; 35(1):130-7. PMID: 21274742.
      View in: PubMed
    23. Li P, Cook JA, Gilkeson GS, Luttrell LM, Wang L, Borg KT, Halushka PV, Fan H. Increased expression of beta-arrestin 1 and 2 in murine models of rheumatoid arthritis: isoform specific regulation of inflammation. Mol Immunol. 2011 Oct; 49(1-2):64-74. PMID: 21855149.
      View in: PubMed
    24. Fan H, Li P, Zingarelli B, Borg K, Halushka PV, Birnbaumer L, Cook JA. Heterotrimeric Ga(i) proteins are regulated by lipopolysaccharide and are anti-inflammatory in endotoxemia and polymicrobial sepsis. Biochim Biophys Acta. 2011 Mar; 1813(3):466-72. PMID: 21255617.
      View in: PubMed
    25. Zingarelli B, Piraino G, Hake PW, O'Connor M, Denenberg A, Fan H, Cook JA. Peroxisome proliferator-activated receptor {delta} regulates inflammation via NF-{kappa}B signaling in polymicrobial sepsis. Am J Pathol. 2010 Oct; 177(4):1834-47. PMID: 20709805.
      View in: PubMed
    26. Guan S, Li P, Luo J, Li Y, Huang L, Wang G, Zhu L, Fan H, Li W, Wang L. A deuterohemin peptide extends lifespan and increases stress resistance in Caenorhabditis elegans. Free Radic Res. 2010 Jul; 44(7):813-20. PMID: 20528576.
      View in: PubMed
    27. Fan H, Bitto A, Zingarelli B, Luttrell LM, Borg K, Halushka PV, Cook JA. Beta-arrestin 2 negatively regulates sepsis-induced inflammation. Immunology. 2010 Jul; 130(3):344-51. PMID: 20465566.
      View in: PubMed
    28. Fan H, Zingarelli B, Harris V, Tempel GE, Halushka PV, Cook JA. Lysophosphatidic acid inhibits bacterial endotoxin-induced pro-inflammatory response: potential anti-inflammatory signaling pathways. Mol Med. 2008 Jul-Aug; 14(7-8):422-8. PMID: 18431464.
      View in: PubMed
    29. Basher F, Fan H, Zingarelli B, Borg KT, Luttrell LM, Tempel GE, Halushka PV, Cook JA. beta-Arrestin 2: a Negative Regulator of Inflammatory Responses in Polymorphonuclear Leukocytes. Int J Clin Exp Med. 2008; 1(1):32-41. PMID: 19079685.
      View in: PubMed
    30. Zingarelli B, Fan H, Ashton S, Piraino G, Mangeshkar P, Cook JA. Peroxisome proliferator activated receptor gamma is not necessary for the development of LPS-induced tolerance in macrophages. Immunology. 2008 May; 124(1):51-7. PMID: 18028370.
      View in: PubMed
    31. Fan H, Williams DL, Zingarelli B, Breuel KF, Teti G, Tempel GE, Spicher K, Boulay G, Birnbaumer L, Halushka PV, Cook JA. Differential regulation of lipopolysaccharide and Gram-positive bacteria induced cytokine and chemokine production in macrophages by Galpha(i) proteins. Immunology. 2007 Sep; 122(1):116-23. PMID: 17484771.
      View in: PubMed
    32. Fan H, Luttrell LM, Tempel GE, Senn JJ, Halushka PV, Cook JA. Beta-arrestins 1 and 2 differentially regulate LPS-induced signaling and pro-inflammatory gene expression. Mol Immunol. 2007 May; 44(12):3092-9. PMID: 17418896.
      View in: PubMed
    33. Fan H, Williams DL, Breuel KF, Zingarelli B, Teti G, Tempel GE, Halushka PV, Cook JA. Gi proteins regulate lipopolysaccharide and Staphylococcus aureus induced cytokine production but not (1--> 3)-beta-D-glucan induced cytokine suppression. Front Biosci. 2006 Sep 01; 11:2264-74. PMID: 16720313.
      View in: PubMed
    34. Fan H, Williams DL, Zingarelli B, Breuel KF, Teti G, Tempel GE, Spicher K, Boulay G, Birnbaumer L, Halushka PV, Cook JA. Differential regulation of lipopolysaccharide and Gram-positive bacteria induced cytokine and chemokine production in splenocytes by Galphai proteins. Biochim Biophys Acta. 2006 Oct; 1763(10):1051-8. PMID: 16962188.
      View in: PubMed
    35. Peck OM, Zingarelli B, Fan H, Teti G, Tempel G, Halushka PV, Cook JA. The phosphatidylinositol 3 kinase pathway regulates tolerance to lipopolysaccharide and priming responses to Staphylococcus aureus and lipopolysaccharide. Shock. 2006 Jul; 26(1):31-6. PMID: 16783195.
      View in: PubMed
    36. Fan H, Zingarelli B, Peck OM, Teti G, Tempel GE, Halushka PV, Spicher K, Boulay G, Birnbaumer L, Cook JA. Lipopolysaccharide- and gram-positive bacteria-induced cellular inflammatory responses: role of heterotrimeric Galpha(i) proteins. . 2005 Aug; 289(2):C293-301. PMID: 15788486.
      View in: PubMed
    37. Fan H, Peck OM, Tempel GE, Halushka PV, Cook JA. Toll-like receptor 4 coupled GI protein signaling pathways regulate extracellular signal-regulated kinase phosphorylation and AP-1 activation independent of NFkappaB activation. Shock. 2004 Jul; 22(1):57-62. PMID: 15201703.
      View in: PubMed
    38. Peck OM, Williams DL, Breuel KF, Kalbfleisch JH, Fan H, Tempel GE, Teti G, Cook JA. Differential regulation of cytokine and chemokine production in lipopolysaccharide-induced tolerance and priming. Cytokine. 2004 Jun 07; 26(5):202-8. PMID: 15157897.
      View in: PubMed
    39. Peck OM, Fan H, Tempel GE, Teti G, Halushka PV, Cook JA. Staphylococcus aureus and lipopolysaccharide induce homologous tolerance but heterologous priming: role of interferon-gamma. Shock. 2004 Mar; 21(3):254-60. PMID: 14770039.
      View in: PubMed
    40. Fan H, Cook JA. Molecular mechanisms of endotoxin tolerance. J Endotoxin Res. 2004; 10(2):71-84. PMID: 15119998.
      View in: PubMed
    41. Fan H, Teti G, Ashton S, Guyton K, Tempel GE, Halushka PV, Cook JA. Involvement of G(i) proteins and Src tyrosine kinase in TNFalpha production induced by lipopolysaccharide, group B Streptococci and Staphylococcus aureus. Cytokine. 2003 Jun 07; 22(5):126-33. PMID: 12842760.
      View in: PubMed
    42. Fan H, Duan Y, Zhou H, Li W, Li F, Guo L, Roeske RW. Selection of peptide ligands binding to fibroblast growth factor receptor 1. IUBMB Life. 2002 Aug; 54(2):67-72. PMID: 12440521.
      View in: PubMed
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