Overview

My long-term research focuses on the role of innate immunity in inflammation and organ injuries associated with
critical illnesses such as sepsis, shock, and trauma. Our recent findings have identified an increase in plasma cell-free
RNA, including miRNAs, during sepsis and trauma.

These extracellular RNAs (exRNAs) are released by host cells and their levels are closely correlated with the severity of sepsis. My research aims to test the hypothesis that exmiRNAs play a critical role in the pathogenesis of acute lung injury and brain inflammation during polymicrobial sepsis.

Additionally, we are also investigating whether exRNAs act as molecular drivers that activate innate
immunity by modulating macrophage function, potentially contributing to trauma-induced inflammation and organ
injury.

To explore these mechanisms, we employ a range of complementary approaches, including genetically
modified animal models, adoptive cell transfer, chimeric models, synthetic oligonucleotides, pharmacological inhibitors, receptor antagonists, and locked nucleic acid-modified anti-miRNA inhibitors. The research is supported by NIH R35GM124775 (PI), R01NS110567 (MPI).

Topics of Focus: 

•  The function and mechanisms of autophagy in SCI
•  Inflammatory mechanisms underlying olfactory dysfunction in prognosis of TBI progression to dementia
•  Mechanism of inflammatory-related brain dysfunction after SCI
•  Role of EVs after CNS Injury: Mechanisms and Modulation
•  Mechanisms and intervention of GA-caused olfactory deficit and its progression to late cognitive impairment
• Targeting cGAS pathway improves functional recovery after CNS injury

Publications

• Park C, Lei Z, Li Y, Ren B, He J, Huang H, Chen F, Li H, Brunner K, Zhu J, Jay SM, Williams B, Chao W, Wu J,
  Zou L. Extracellular vesicles in sepsis plasma mediate neuronal inflammation in the brain through miRNAs
  and innate immune signaling. J Neuroinflammation. 2024 Oct 7;21(1):252. PMID: 39375720.
• Suen AO, Chen F, Wang S, Li Z, Zhu J, Yang Y, Conn O, Lopez K, Cui P, Wechsler L, Cross A, Fiskum G, Kozar
  R, Hu P, Miller C, Zou L, Williams B, Chao W. Extracellular RNA Sensing Mediates Inflammation and Organ
  Injury in a Murine Model of Polytrauma. J Immunol. 2023 Jun 15;210(12):1990-2000. PMID: 37133342.
• Huang H, Zhu J, Gu L, Hu J, Feng X, Huang W, Wang S, Yang Y, Cui P, Lin SH, Suen A, Shimada BK, Williams B,
  Kane MA, Ke Y, Zhang CO, Birukova AA, Birukov KG, Chao W, Zou L. TLR7 Mediates Acute Respiratory
  Distress Syndrome in Sepsis by Sensing Extracellular miR-146a. Am J Respir Cell Mol Biol. 2022
  Sep;67(3):375-388. PMID: 35679261.
• Wang S, Yang Y, Suen A, Zhu J, Williams B, Hu J, Chen F, Kozar R, Shen S, Li Z, Jeyaram A, Jay SM, Zou L, Chao
  W. Role of extracellular microRNA-146a-5p in host innate immunity and bacterial sepsis. iScience. 2021 Nov
  13;24(12):103441. PMID: 34877498.
• Zou L, He JY, Gu L, Shahror AR, Li Y, Cao T, Wang S, Zhu J, Huang H, Chen F, Fan X, Wu J, Chao W. Brain
  Innate Immune Response via miRNA-TLR7 Sensing in Polymicroblial sepsis. Brain Behav Immun. 2022
  Feb:100:10-24. PMID: 34808293.
• Jian W, Gu L, Williams B, Feng Y, Chao W, Zou L. Toll-like Receptor 7 Contributes to Inflammation, Organ
  Injury, and Mortality in Murine Sepsis. Anesthesiology. 2019 Jul;131(1):105-118. PMID: 31045897.

Please see Dr. Zou's faculty profile for a complete list of his publications.

You can also see his publications on PubMed.

Contact

Office: (410) 706-2547
Email:  lzou@som.umaryland.edu