Research

Major Research Areas: Natural Product Chemistry and Cell Signaling

  1. Molecular Mechanisms of Chinese Medicines: Application of biological response spectrum and cell signaling approaches to define the mechanisms for complex Chinese medicines
  2. Biology of interferon and cytokines in microbial infections – signaling pathways and gene regulation (e.g., HIV and Mycobacterium) 
  3. Development of technology platform for drug discovery: applying a combination of molecular techniques for purification and identification of bioactive molecules in medicinal herbs.

Examples of Recent Research Projects: 

As an example of platform technology development, we recently investigated the immunomodulatory effects of Panax ginseng (Ginseng). Ginseng is one of the most commonly used CM worldwide and contains a mixture of constituents with multiple effects on neuroendocrine, immune and cardiovascular systems in humans.  Using human immune cells as a model, we performed detailed analyses on the chemical and biological effects of its bioactive constituents, ginsenosides, on gene activation and cell functions. We have delineated the biological pathways and cell signalling regulators controlled by individual ginsenosides and their effects on the production of inflammatory factors known as cytokines. By reconstitution of selected ginsenosides into a definable mixture without other inactive ingredients, we can reproduce the same biological effects (published in J Translational Medicine 2009).          

In collaboration with British Columbia Genome Science Centre, we have identified a series of small-molecule inhibitors against influenza viruses including human and avian viruses through computational screening against the viral genes. Computational molecular docking provides an efficient and innovative approach to examine small molecule and protein interactions. We have utilized this method to identify potential inhibitors of the H5N1 neuraminidase protein and other key viral genes (J Medicinal Chemistry, May 2009).  .

In another example, we examined the biological effects of Black Cohosh and its Chinese counterpart Shengma (Cimicifuga species). Cimicifuga species have been used as traditional medicinal herbs to treat inflammation and symptoms associated with menopause in Asia, Europe and North America.  However, the underlying mechanism of their anti-inflammatory effects was unknown. With bioactivity guided purification involving the use of partitioning extraction and high performance liquid chromatography, we have successfully isolated the key bioactive constituents from the rhizome extracts of Cimicifuga racemosa. By NMR spectroscopy, the molecular structure of the compound was identified.  Further, we have defined its regulatory effects on cell signaling pathways in the immune cells (J Medicinal Chemistry, November 2009).
In summary, we have developed and tested our platform technology for unraveling the mystery of traditional Chinese Medicine by applying chemical authentication, genomics and cell signaling technologies to delineate the molecular mechanisms of medicinal herbs.  Thus, understanding the mechanisms of action of TCM supports the rationales and scientific ground for the use of medicinal herbs in the treatment of diseases.


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