Fu, Jian, Ph.D.

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Contact: jian.fu@uthct.edu

Education:
Ph.D. 2001, Physiology and Biophysics, University of Alabama at Birmingham.

Research Interest:
Lung Inflammation, Injury and Repair; Innate Immunity; Lung Vascular Biology; Critical Care Medicine.

Honors/Awards:
2005 - 2007 - Parker B. Francis Fellowship Award in Pulmonary Research.
2005 - 2008 - American Heart Association Scientist Development Award (National Research Program).

Grant Advisory & Review Services:
2012 Member, AHA (American Heart Association) Peer Review Committee: Lung Clinical study section
June 2012 Member, NIH LCMI (Lung Cellular, Molecular, And Immunobiology) Study Section
October 2011 Member, NIH RIBT (Respiratory Integrative Biology and Translational Research) Study Section
2011- Member, Grant Review Committee: COPD and Emphysema Panel; Flight Attendant Medical Research Institute (FAMRI), USA.
2010 Grant Reviewer; Developmental Idea Award for Center of Excellence on Treatment of Second Hand Smoke Effects; Flight Attendant Medical Research Institute (FAMRI), USA.
2009 Member, Grant Review Committee: Respiratory Effects of Second Hand Tobacco Smoke Exposure; Flight Attendant Medical Research Institute (FAMRI), USA.
2007 Member of Grant Review Panel; Research on diseases associated with second hand smoke; Flight Attendant Medical Research Institute (FAMRI), USA.
Editorial Board: 2012-Present Academic Editor- PLOS ONE.
Journal Reviewer - Critical Care Medicine, Journal of Immunology, Journal of Biological Chemistry, Journal of Pharmacology and Experimental Therapeutics, Molecular Pharmacology


Research Overview:
Sepsis-induced lung and vascular inflammation and injury. Sepsis often leads to multi-organ failure and death due to systemic inflammatory injury and bacterial infection. Acute respiratory distress syndrome (ARDS) is one of the major causes of death in sepsis. It has been estimated that there are about 750,000 cases of sepsis annually in the United States. Many studies have demonstrated that activation of complex inflammatory networks rather than a single inflammatory mediator leads to the excessive inflammatory responses in sepsis, which may explain why current therapeutic strategies targeting a single inflammatory mediator have thus far failed to improve outcomes in the clinical trials. Therefore, new therapeutic strategies that can provide a better control of the inflammatory networks are desperately needed to treat/prevent this devastating disease. NF-κB is a transcription factor that has been known to regulate the expression of a wide variety of pro-inflammatory mediators. NF-κB functions as a master regulator of several inflammatory pathways in sepsis. Increased NF-κB activation has been well-recognized as a key pathological mechanism in sepsis. Blockade of NF-κB has been shown to prevent the production of multiple pro-inflammatory mediators, inhibit vascular inflammatory injury and improve survival in murine models of septic shock. However, the regulation of NF-κB pathway in sepsis remains largely unknown. Recent studies have also established a critical role of the mitochondria-regulated intrinsic apoptotic pathway in lung endothelial and alveolar epithelial cell apoptosis. In this project, we will investigate molecular regulation of NF-κB in sepsis-induced vascular inflammation and explore the regulation of intrinsic apoptotic pathway in sepsis-induced lung injury.

Particulate matter air pollution-induced lung and vascular dysfunction. Acute exposure to increased ambient fine particulate matter < 2.5 µm in diameter (PM2.5) was estimated to cause premature deaths of tens of thousands of people each year in the United States. Despite the enormous health problems caused by PM exposure, there have been few studies to explore molecular mechanisms of PM-induced lung injury and vascular dysfunction, which has greatly hampered our understanding on PM-induced lung diseases and development of therapeutic strategies. PM can reach deep in the lung to the small airway and alveoli and directly cause lung inflammation and injury. The pulmonary complications may lead to detrimental effects on other organs, particularly cardiovascular dysfunction such as systemic microvascular dysfunction, coagulation and thrombosis. Several studies published recently have established a critical role of lung cell apoptosis in PM-induced lung injury. However, molecular mechanisms of PM-induced lung injury and pulmonary vascular dysfunction remain largely unknown. In a mouse model, we demonstrated that PM2.5 exposure led to increased lung injury and coagulation in mouse lungs, which correlated with increased lung inflammation. Our studies also showed that PM2.5 exposure induced NF-κB activation in mouse lungs, which was associated with decreased expression of anti-coagulant proteins in lung endothelial cells. In this project, we will investigate molecular mechanisms of lung inflammation, coagulation and injury following PM2.5 exposure.

Selected Papers and Abstracts:

• Wu Z., Liu M., Liang M., Fu J. (Corresponding author). Sirt1 protects against thrombomodulin down-regulation and lung coagulation after particulate matter exposure. Blood 119(10):2422-29, 2012.
• Shetty SK, Marudamuthu AS, Abernathy D, Shetty RS, Shetty P, Fu J, Idell S, Bhandary YP, Ji H, Liu MC, Shetty S. Regulation of urokinase expression at the posttranscription level by lung epithelial cells. Biochemistry. 2011 Dec 14. [Epub ahead of print].
• Yasuda S., Yasuda T., Liu MY., Shetty S., Idell S., Boggaram V., Suiko M., Sakakibara Y., Fu J., Liu MC. Sulfation of Chlorotyrosine and Nitrotyrosine by Human Lung Endothelial and Epithelial Cells: Role of the Human SULT1A3. Toxicology and Applied Pharmacology 251(2): 104–109, 2011.
• Wu Z., Sawamura T., Kurdowska AK., Ji HL., Idell S., Fu J. LOX-1 deletion improves neutrophil function, enhances bacterial clearance and reduces lung injury in a murine polymicrobial sepsis model. Infection and Immunity 79(7):2865-2870, 2011.
• Han D., Nie H., Gu X., Nayak R., Su X., Fu J., Chang Y., Rao V., Ji H. K+ channel openers restore verapamil-inhibited lung fluid resolution and transepithelial ion transport. Respiratory Research 11:65, 2010.
• Zhang P, Cheng L, Liang M, Liu MC, Ji HL, Fu J. Blockade of LOX-1 prevents endotoxin-induced lung inflammation and injury in mice. Journal of Innate Immunity 1(4):358-365, 2009.
• Low B, Liang M, Fu J. p38 Mitogen-Activated Protein Kinase Mediates Sidestream Cigarette Smoke-Induced Endothelial Permeability. Journal of Pharmacological Sciences 104(3): 225-231, 2007.
• Gao XP, Zhu XD, Fu J, Liu QH, Frey RS, Malik AB. Blockade of Class IA Phosphoinositide 3-Kinase in Neutrophils Prevents NADPH Oxidase Activation- and Adhesion- Dependent Inflammation. Journal of Biological Chemistry 282(9):6116-25, 2007.
• Ge X, Low B, Liang M, Fu J. Angiotensin II directly triggers endothelial exocytosis via protein kinase C-dependent protein kinase D2 activation. Journal of Pharmacological Sciences 105(2): 168-176, 2007.
• Yasuda S, Idell S, Fu J, Carter G, Snow R, Liu MC. Cigarette smoke toxicants as substrates and inhibitors for human cytosolic SULTs. Toxicology and Applied Pharmacology 221(1):13-20, 2007.
  Liang M, Zhang P, Fu J. Up-regulation of LOX-1 expression by TNF-alpha promotes trans-endothelial migration of MDA-MB-231 breast cancer cells. Cancer Letters 258(1): 31-37, 2007.
• Fu J, Naren AP, Gao XP, Ahmmed GU, Malik AB. Protease-activated receptor-1 activation of endothelial cells induces protein kinase Calpha-dependent phosphorylation of syntaxin 4 and Munc18c: role in signaling p-selectin expression. Journal of Biological Chemistry 280(5):3178-84, 2005.
• Ji HL, Jovov B, Fu J, Bishop LR, Mebane HC, Fuller CM, Stanton BA, Benos DJ. Up-regulation of acid-gated Na+ channels (ASICs) by CFTR co-expression in Xenopus oocytes. Journal of Biological Chemistry, 277(10):8395-405, 2002.
• Fu J, Kirk KL. Cysteine substitutions reveal dual functions of the amino-terminal tail in cystic fibrosis transmembrane conductance regulator channel gating. Journal of Biological Chemistry 276(38):35660-668, 2001.
• Fu J, Ji HL, Naren AP, Kirk KL. A cluster of negative charged residue at the amino terminal tail of CFTR regulates ATP-dependent channel gating. Journal of Physiology 536(2):459-470, 2001.
• Naren AP, Boyaka E, Fu J, Villain M, Blalock E, Quick MW, Kirk KL. CFTR chloride channel regulation by an interdomain interaction. Science 286(5439): 544-548, 1999.