The two areas of research in my laboratory are 1). a transgenic mouse model system for melanoma development. and 2). Regulation of cell signaling by G-protein-coupled-receptor:
Malignant melanoma, a very aggressive type of skin cancer, if detected and removed at an early stage, the overall 5-year survival rate is relatively high. However, if the lesions are not detected and removed at an early stage, metastasis may occur and spread to other parts of the body, which is associated with high mortality rate. Currently, malignant melanoma is largely refractory to conventional therapies.
A transgenic mouse line that displays melanoma phenotype spontaneously was developed in our lab. We showed and confirmed the aberrant expression of a G-protein-coupled-receptor (metabotropic glutamate receptor 1. Grm1) in melanocytes to be responsible for the generation of melanoma in our system. Expression of GRM1 has been detected in some human melanoma cell lines and biopsy samples, suggesting possible involvement of this receptor in some cases of human melanoma. Normally Grm1 is predominantly associated with excitatory synaptic neurotransmission in the mammalian central nervous system. The signaling cascades activated by the ligand, glutamate, are believed to be equally important in regulating the growth and differentiation of a wide variety of both neural and non-neural cells. We hypothesize that one of the consequences of deregulation of Grm1 expression in melanocytes is activation of pathways leading to increase in cell proliferation and/or decrease in apoptosis, resulting in cell transformation and tumor development. The long term goals of our lab are to identify and characterize the signaling pathway(s) utilized by Grm1 ectopically expressed in melanocytes, and downstream targets of the oncogenic effects exerted by activated Grm1 in our system and to use our model system to better understand this complex disease and apply our knowledge to development of more effective agents with fewer side effects for the prevention and treatment of cancer.
