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Yuan Lab

Research

Glycocalyx

Overview

The human body is extremely effective at maintaining homeostasis and protecting itself from injury and infection through the inflammatory response of the immune system. Dysregulation of this protective immune response, however, can lead to microvascular barrier dysfunction worsening disease prognoses and treatment outcomes. Our lab studies several disease states, including sepsis, cardiovascular disease (e.g. atherosclerosis, diabetes), trauma, inflammation, and immunological disorders to elucidate the physiological mechanisms that contribute to the dysregulated host response to infection and injury. Our work aims to produce translational research with the goal of improving diagnostic tools and therapies for a multitude of disease states related to vascular barrier injury. 


  • Macrophage Efferocytosis in Lung Disease

    Efferocytosis is defined by the clearance of apoptotic cells by phagocytes, like macrophages, through a finely tuned, multistep process. If not removed in a timely manner, apoptotic cells accumulate and can undergo secondary necrosis, which releases proinflammatory intracellular components and induces inflammation. This project aims to unravel the underlying mechanisms behind impaired macrophage efferocytosis in sepsis, pneumonia, and acute lung injury to identify potential therapeutic targets.

  • Lymphopenia in Ischemic Heart Failure

    Cardiovascular disease (CVD) is the leading cause of death globally, and includes stroke, atherosclerosis, and myocardial infarction, among others. Lymphopenia, on the other hand, is characterized by a reduction in peripheral blood B and T lymphocyte counts. Emerging clinical studies have shown that lymphopenia correlates with worse cardiac function and poor outcomes in patients with myocardial infarction (MI). This project aims to elucidate how cardiac ischemia induces lymphopenia and determine whether targeting lymphopenia can effectively improve post-ischemic cardiac repair. 

  • Blood-Brain Barrier Dysfunction in Systemic Inflammation

    This research project focuses on the mechanisms that connect lung infection and brain dysfunction. Our investigators study the detrimental effects that the immune response, triggered by lung bacterial infection, has on the highly specialized brain endothelial cells that constitute the blood-brain barrier. This project utilizes in vitro approaches using primary mouse brain endothelial cells and an in vivo mouse model of lung infection by intratracheal administration of Pseudomonas aeruginosa cultures.

  • Extracellular Vesicles in Thermal Injury

    Extracellular vesicles (EVs) are nano-sized membrane-bound particles containing biologically active cargo molecules. We comprehensively analyze the plasma EVs from burn patients and healthy subjects, characterizing their size distribution, concentration, temporal changes, cell origins, and cargo protein contents. The goal of this project is to investigate the biomarker roles of burn EVs in reflecting burn severity and predicting the clinical outcomes for burn patients. In addition, we evaluate the pathological roles of EVs in burn-induced systemic inflammation.

Selected Publications

1. Yuan Y, Granger HJ, Zawieja DC, DeFily DV, and Chilian WM. Histamine increases venular permeability via a phospholipase C-NO synthase-guanylate cyclase cascade. Am J Physiol. 264: H1734-H1739, 1993. PMID: 7684577 
 
2. Yuan SY, Ustinova EE, Wu MH, Tinsley JH, Xu W, Korompai FL, and Taulman AC.  PKC activation contributes to microvascular barrier dysfunction in the heart at early stages of diabetes.  Circulation Research 87: 412-417, 2000. PMID: 10969040 
 
3. Yuan SY, Wu MH, Ustinova EE, Guo M, Tinsley JH, De Lanerolle P, and Xu W.  Myosin light chain phosphorylation in neutrophil-stimulated coronary microvascular leakage. Circulation Research 90: 1214-1221, 2002. PMID: 12065325. *Selected for Editorial Highlight. 
 
4. Gaudreault N, Perrin RM, Guo M, Clanton CP, Wu MH, and Yuan SY. Counter regulatory effects of PKCbII and PKCd on coronary endothelial permeability. Arterioscler Thromb Vasc Biol 28: 1527-1533, 2008. PMCID: PMC2626185 
 
5. Shen Q, Lee ES, Pitts RL, Wu MH, and Yuan SY. TIMP-2 regulates MMP-2 mediated endothelial barrier dysfunction and breast cancer cell transmigration through lung microvascular endothelial cells. Mol Cancer Res 8:939-951, 2010. PMID: 20571065. *Selected for Editorial Highlight. * Selected for Journal Cover Page  
 
6. Sun C, Wu MH, and Yuan SY.  nmMLCK deficiency attenuates atherosclerosis in ApoE-deficient mice via reduced endothelial barrier dysfunction and monocyte migration. Circulation 124: 48-57, 2011. PMCID: PMC3136817. * Selected for Editors’ Picks: Most Read Articles in Atherosclerosis 
 
7. Beard RS Jr Jr, Haines RJ, Wu KY, Reynolds JJ, Davis SM, Elliott JE, Malinin NL, Chatterjee V, Cha B, Wu MH, and Yuan SY. Non-muscle MLCK is required for β-catenin/FoxO1-dependent downregulation of claudin-5 in interleukin-1β-mediated barrier dysfunction in brain endothelial cells.  J Cell Sci 127: 1840-1853, 2014. PMCID: PMC4074294 
 
8. Beard RS Jr, Yang X, Meegan JE, Overstreet JW, Yang C, Elliott JA, Renoylds JJ, Cha BJ, Pivetti CD, Mitchell DA, Wu MH, Deschenes RJ, and Yuan SY. Palmitoyl acyltransferases DHHC21 mediates endothelial dysfunction in systemic inflammatory response syndrome.  Nature Communications 7:12823, 2016.  PMCID:PMC5036164 
 
9. Yang X, Meegan JE, Jannaway M, Coleman DC and Yuan SY. A disintegrin and metalloproteinase 15-mediated glycocalyx disruption contributes to vascular leakage during septic injury. Cardiovascular Research 114(13): 1752-1763, 2018. PMID: 29939250. *Selected for Editorial Highlight. 
 
10. Beard RS Jr, Hoettels BA, Meegan JE, Wertz TS, Cha BJ, Yang X, Oxford JT, Wu MH, and Yuan SY. AKT2 maintains brain endothelial cell claudin-5 expression and selective activation of IR/AKT2/FOXO1-signaling reverses BBB dysfunction. J Cereb Blood Flow Metab 40(2): 374-391, 2020. PMID:30574832. 
 
11. Chatterjee V, Yang X, Ma Y, Cha B, Meegan JE, Wu MH and Yuan SY. Endothelial microvesicles carrying c-Src cargo impair adherens junction integrity and cytoskeleton homeostasis. Cardiovascular Research 116(8):1525-1538, 2020. PMID:31504252. 
 
12. Villalba N, Baby Sheon, Cha BJ, Yuan SY. Site-specific opening of the blood-brain barrier by extracellular histones. J Neuroinflammation 17(1): 281, 2020. PMID: 32962721.