Research Focus

Establishment of a pre-clinical animal models for herbal medicine and molecular vaccine research

We anticipate the needs of our fellow institute members for human xenografts and syngenic tumors in mice, xenografts as grown in nude mice or SCID to facilitate primary tumor growth or metastasis evaluation, and syngenic tumors as grown in most mice species. Our experiences in traditional subcutaneous, orthotopic, and other models enable us to customize models to meet specific needs. We have conducted studies involving culture and inoculation of tumor cell lines, monitoring, and measurement of tumor growth, administration of therapeutic or preventative dosing protocols, excision and collection of tumors, and necropsy with observation for sites. We are also familiar with imaging/x-ray systems, and progressive equipment for anatomical localization of molecular imaging agent signals in small animals, organs, and tissues, and can take advantage of multiple imaging modalities including multi-wavelength fluorescent, luminescent, and x-ray.

Skeletal muscle development

We have investigated the role of myostatin in skeletal muscle development using both in vivo and in vitro systems. Myostatin is a member of the transforming growth factor β superfamily. It is reported that myostatin is a negative regulator of skeletal muscle growth. The recent studies investigated the role of myostatin in skeletal muscle development in an L8 cell culture system and the application of myostatin in animal growth. First, recombinant myostatin protein was expressed and purified from a baculovirus expression system. In the L8 culture system, recombinant myostatin protein inhibited the proliferation and differentiation of L8 myoblasts. In addition, recombinant myostatin inhibited total protein synthesis in L8 myotubes; however, protein degradation was not altered by myostatin. Second, maternal immunization against myostatin was attempted in order to enhance the growth performance in offspring. It was concluded that myostatin plays a crucial role in myogenesis and regulation of protein synthesis and maternal myostatin immunization enhances the growth performance of offspring.

Suppression of drug-resistant cancer growth and metastasis using metabolic modulators

Carcinogenesis is a multistage event affected by a variety of genetic and epigenetic factors and it is typified by an outbreak of uncontrolled cell growth originating in various tissues. The universal goal in anticancer research is the development of a clinical treatment that is highly effective in curtailing of tumor growth, non-toxic to the host, and affordable for most patients. Our approach to overcoming MDR1/Pgp-mediated MDR is unique in that it involves the use of a compound which itself is a potent anticancer agent. Tetra-O-methyl nordihydroguaiaretic acid (M4N, Terameprocol) is a nontoxic compound from the plant Larrea tridentate. Long-term toxicity tests for M4N have been carried out in mice during two courses, one of 14 weeks and one of 6 months during which the average oral uptake of M4N was 90 mg/mouse/day. No deaths and no significant body weight differences were observed between control mice and treated mice. In addition, M4N treatment caused no gastrointestinal disorders, anemia, or hair loss in dogs, rats, and rabbits. Nevertheless, M4N was shown to suppress the growth of a variety of mice and human tumor cells and human tumor explants in nude mice.

M4N causes cell cycle arrest at the G2 phase of cell cycle probably by suppressing Sp-1 regulated cdc2 expression. Most significantly our previous results also showed that M4N is able to inhibit MDR1 gene expression in multi-drug resistant NCI/ ADR-RES cells. In addition, M4N was found to inhibit doxorubicin-induced MDR1 gene expression in drug sensitive MCF-7 breast cancer cells without building up resistance to doxorubicin following long-term treatment.