Research

Fu, Jian, Ph.D.

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Contact: jian.fu@uthct.edu

Education:
Ph.D. 2000, Physiology and Biophysics, University of Alabama at Birmingham

Research Interest:
Cancer immunology; Lung inflammation and injury

Current Projects:

  1. Modulation of cancer cell-reactive immune responses.
  2. Mechanisms of lung inflammation and injury.

Research Overview:
Modulation of cancer cell-reactive immune responses. Immunotherapy has shown great promise in cancer treatment. However, resistance of cancer cells to immunotherapy remains a big challenge. Thus, developing new agents that can modulate cancer cell-reactive immune responses is necessary for the improvement of the efficacy of immunotherapy.

Programmed death-1-ligand 1 (PD-L1) is a cell surface protein of B7 family. PD-L1 is one of the two ligands for program death receptor 1 (PD-1), a co-stimulatory molecule that negatively regulates T cell immune responses. It is now well accepted that PD-L1 expression in cancer cells contributes to immunoresistance. The expression of PD-L1 has been detected in a variety of solid tumors but not in normal tissue. Furthermore, PD-L1 expression on carcinomas is correlated with poor clinical prognosis of renal, gastric carcinomas, breast cancers and esophageal cancers. Ligation of PD-L1 expressed on cancer cells to PD-1 expressed on T cells has been shown to suppress T cell activation and proliferation, and induce T cell apoptosis. PD-L1 blockade using PD-L1 antibody was able to induce anti-tumor immunity and inhibit tumor growth. Therefore, increased PD-L1 expression in cancer cells could be an important escape mechanism from the host T cell immunity.

Given the critical role of PD-L1 in cancer cell-reactive T cell immune suppression, blockade of PD-L1/PD-1 pathway could be a valuable approach to improve cancer immunotherapy. Our current projects are to investigate the mechanisms of PD-L1 surface expression in breast cancer cells, and to determine the role of PD-L1-mediated T cell suppression in breast cancer immune evasion. Through our studies, we hope to identify a new class of therapeutic agents that may possess dual functions to inhibit cancer cell growth and boost anti-cancer immunity.

Mechanisms of lung inflammation and injury. Acute lung injury (ALI) is usually associated with excessive pulmonary inflammation. Neutrophil accumulation in the lung plays a crucial role in both the onset and progression of ALI. Production and up-regulation of pro-inflammatory mediators such as ICAM-1, P-selectin, TNF-alpha, and NF-κB have been reported to contribute to LPS-induced lung inflammation. Increased apoptotic signaling has been demonstrated in LPS-induced lung vascular injury. The extensive neutrophil influx to the lung requires pro-inflammatory signals capable of supporting both the early recruitment and persistent influx of neutrophils. The initial recruitment of neutrophils to the lung may require early signals such as the expression of ICAM-1 and P-selectin in lung endothelial cells that mediate neutrophil adhesion and migration across the lung vasculature. Persistent neutrophil influx may require additional mediators such as pro-inflammatory cytokine CXCR4/SDF-1. Despite the considerable progress made in elucidating the pro-inflammatory mediators that contribute to ALI, it is likely that some of the key mediators remain unidentified. The research interest of my lab in this area is to uncover the mechanisms of acute lung inflammation and injury, and to identify new mediators of lung injury that may serve as potential targets for therapeutic intervention.

Selected Papers and Abstracts: