Guoshun Wang, DVM, PhD

The Wang lab has several research directions, including 1) cystic fibrosis (CF) pathogenesis and CF gene and stem cell therapy, 2) chloride anion and phagocytic innate immunity, and 3) alcohol-directed anti-inflammation and immunosuppression.

CF, one of the most fatal genetic diseases in the white population, is caused by mutations in CF transmembrane conductance regulator (CFTR), a cAMP-activated chloride channel. Over 90% of CF patients die of uncontrollable bacterial infections of the lungs.  It is not fully defined how the chloride channel defect leads to the lung host defense failure. The Wang lab has provided the first evidence that the CFTR defect results in deficient chloride transport to neutrophil phagosomes.  Such a deficiency impairs the production of hypochlorous acid (HOCl), the chlorine bleach, in the organelle for effective bacterial killing. Currently, the lab is further characterizing the importance of this defect in CF lung pathogenesis and is also pursuing molecular therapies to correct the defect. 

Chloride is the most abundant anion in human body. This anion plays an important role in regulating cell volume and pH, and equilibrating resting membrane potential. However, neutrophils use this anion in a special way to generate HOCl, a most potent microbicidal oxidant.  Molecular mechanisms underlying the acquisition by cells of this anion from the extracellular environment and how they further transport it to phagosomes are not well defined. The lab is currently engaged in characterizing which chloride channels are involved in this ion transport process in neutrophils.

Alcohol has long been recognized to have antiiinflammatory and immunosuppressive effects. However, the molecular mechanisms underlying this phenomenon are not well defined.  Previous research from this lab has shown that ethanol upregulates Glucocorticoid-induced Leucine Zipper, a steroid-responsive gene, thus modulating cell cytokine expression and secretion.  We are now characterizing how alcohol utilizes the glucocorticoid signaling pathway to modulate immune cell status.