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Hongkuan Fan PhD

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  • Associate Professor
  • College of Medicine
  • Pathology and Laboratory Medicine
Academic Focus
  • The Role of Pericytes in the Vascular Dysfunction of Sepsis
  • The Role of Pericytes in Neurovascular Function in Alzheimer's Disease Development
  • The Role of lncRNA Neat1/Hbb axis in aging and Alzheimer's disease
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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





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.


 Alzheimer's Disease (AD) is the most common senile dementia, causing severe and permanent impairment of both cognitive and behavioral functions. It accounted for about 70 percent of the 50 million dementia patients worldwide in 2018, and this figure is anticipated to triple by 2050 with associated costs approaching 4 trillion dollars. AD pathology is characterized by the extracellular deposition of amyloid plaques consisting predominantly of amyloid-β peptides and the intraneuronal accumulation of neurofibrillary tangles comprised of aggregated, hyperphosphorylated tau proteins. Recent studies have demonstrated that cerebrovascular alterations are a major cause of dementia and are also a key component of AD pathogenesis. Most recent studies highlight the importance of capillary dysfunction in altering cerebral blood flow (CBF) and blood-brain barrier (BBB) dysfunction in AD.


Pericytes form part of the neurovascular unit (NVU) to meet brain’s energy demands and facilitate neuro-inflammatory responses. Thus, pericyte dysfunction may underlie or exacerbate neurodegenerative diseases such as AD. However, the processes that govern pericyte dysfunction and the role of pericytes in decreases of CBF in AD development have not been fully elucidated. The overall objective of this project is to identify the determinants of brain pericyte function and the potential role of pericytes in brain hypoperfusion in AD.


Recent studies have indicated that long noncoding RNAs (lncRNA) are key mediators in the development and progression of various neurodegenerative disorders, including AD. However, the mechanism of age-associated lncRNA in AD development remains largely unknown.   We uncovered unexpected effects of lncRNA Neat1 and hemoglobin subunit ? (Hbb) on synapse dysfunction. The overall objective of this project is to investigate the Neat1/Hbb axis as a critical determinant of cognitive impairment in aging and AD.




R35 GM149203-01

The Role of Pericytes in the Vascular dysfunction of Sepsis



The Role of Pericytes in Brain Hypoperfusion in Alzheimer's Disease Development




  1. Li P, Wu Y, Goodwin AJ, Wolf B, Halushka PV, Wang H, Zingarelli B, Fan H. Circulating extracellular vesicles are associated with the clinical outcomes of sepsis. Front. Immunol. 2023. 14:1150564. doi: 10.3389/fimmu.2023.1150564 (IF: 8.786)


  2. Wu Y, Li P, Liu L, Goodwin AJ, Halushka PV, Hirose T, Nakagawa S, Zhou J, Liu M, Fan H. lncRNA Neat1 regulates neuronal dysfunction post sepsis via stabilization of hemoglobin subunit beta. Mol Ther. 2022. Mar 21: S1525-0016(22)00170-8. PMID: 35331906. (IF:12.91)


  3. Li P, Wu Y, Hamlett ED, Goodwin AJ, Halushka PV, Carroll SL, Liu M, Fan H. Suppression of Fli-1 protects against pericyte loss and cognitive deficits in Alzheimer's disease. Mol Ther. 2022, 30(4):1451-1464. PMID: 35038582. (IF: 12.91)


  4. 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, 101(5):625-635. (IF:5.511)


  5. 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, 17;222(6):1037-1045. (IF:7.759)


  6. 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, 23(1)44. (IF:19.344)


  7. 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, 108:1-7. (IF:4.174)


  8. 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, 218(12):1995-2005. (IF:7.759)


  9. 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. (IF:12.91)


  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. (IF:19.344)


  11. 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.(IF: 30.528)