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Hongkuan Fan Ph.D.

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Rank
  • Assistant Professor
College
  • College of Medicine
Department
  • Pathology and Laboratory Medicine
Academic Focus
  • Vascular dysfunction in sepsis
  • Progenitor cells, exosomes and miRNAs for sepsis therapy
  • Role of gut microbiota in sepsis

Locations

Office Location
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Biography

 

EDUCATION:

Advanced Education: Ph.D., Jilin University, China, 2001

Postdoctoral Training: New Mexico Tech. USA, 2001-2002

Postdoctoral Training: Medical University of SC, USA, 2002-2006

 

RESEARCH INTERESTS:

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.

 

 

FUNDING:

NIH1R01GM113995-01

The Beneficial Effects of Endothelial Progenitor Cells in the Vascular Dysfunction of Sepsis

NIH R01GM130653-01

The Role of Pericytes in the Vascular Dysfunction of Sepsis

 

SELECTED PUBLICATIONS:

1. Fan H, Bitto A, Zingarelli B, Luttrell LM, Borg KT, Halushka PV, Cook JA. Beta-arrestin 2 negatively regulates sepsis-induced inflammation.  Immunology. 2010, 130 (3): 344-51.

2.. Zingarelli B, Piraino G, Hake PW, O’Connor M, Denenberg A, Fan H, Cook JA. PPARδ regulates systemic inflammation via the NF-κB signaling pathway in polymicrobial sepsis. Am. J. Pathol., 2010, 177(4): 1834-47.

3. Fan H, Li P, Zingarelli B, Borg KT, Halushka PV, Birnbaumer L, Cook JA. Heterotrimeric Gai proteins are regulated by lipopolysaccharide and are anti-inflammatory in endotoxemia and polymicrobial sepsis. Biochim Biophys Acta. 2011, 1813(3): 466-72.

4. 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, 49(1-2):64-74.

5. 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, 35(1):130-7.

6. Li P, Neubig RR, Zingarelli B, Borg KT, Halushka PV, Cook JA, Fan H. Toll-like receptor-induced inflammatory cytokines are suppressed by Gain of function or overexpression of Gai2 protein. Inflammation. 2012, 35(5):1611-7.

7. Fan H. Beta-arrestin 1 and 2 are critical regulators of inflammation. Innate Immun. 2013, 20(5):451-460.

8. Fan H, Goodwin AJ, Chang E, Zingarelli B, Borg K, Guan S, Halushka PV, Cook JA. Endothelial progenitor cells and a SDF-1α analogue synergistically improve survival in sepsis. Am J Respir Crit Care Med. 2014, 189(12):1509-19.

9. 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, 144(3):405-411.

10. Goodwin AJ, Guo C, Cook JA, Wolf B, Halushka P, Fan H. Plasma levels of microRNA are altered with the development of shock in human sepsis: an observational study. Crit Care. 2015, 19:440.

11. Guo C, Goodwin AJ, Buie JN, Cook JA, Halushka PV, Argraves K, Zingarelli B, Zhang XK, Wang L, Fan H. A Stromal Cell-derived Factor 1 alpha Analogue Improves Endothelial Cell Function in Lipopolysaccharide-induced Acute Respiratory Distress Syndrome. Mol Med. 2016, 22: 115-123.

12. Jones Buie JN, Goodwin AJ, Cook JA, Halushka PV, Fan H. The role of miRNAs in cardiovascular disease risk factors. Atherosclerosis 2016, 254:271-281. Review.

13. 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, 26(5): 1375-1384.

14. 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. Jul 20. [Epub ahead of print]

15. 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. 2018 Sep 23. [Epub ahead of print]