Hui Li, PhD
Trans-splicing of mRNA as a novel method of generating chimeric oncogenes in endometrial cancers
A recurrent chromosomal translocation in endometrial stroma tumors results in a fusion between the 5' of the JAZF1 gene and 3' of JJAZ1 gene. JAZF1 gene encodes a putative transcription factor. But the function of the protein is essentially unknown. JJAZ1/SUZ12 encodes a core component of Polycomb Complex 2 (PRC2), which methylates histone H3K27 and causes compacting of chromatin structure. Gene fusion has long been considered a unique feature of neoplasms. Our recent findings have turned the dogma on its head. Chimeric JAZF1-JJAZ1 RNA is identified to be present in normal tissues through a trans-splicing mechanism. One burning question is that how broad the trans-splicing phenomenon is. Based on some preliminary data, we believe it is more common than just a few isolated cases. What is more important is that the trans-splicing might play a critical role in normal development as well as cancer initiation. The lab is also studying the oncogenic effect of JAZF1-JJAZ1 fusion and JAZF1-PHF1 fusion in the endometrial stroma tumor.
Recent Genome Wide Association Studies (GWAS) have identified SNPs in JAZF1 gene that gives carrier higher risk of type 2 diabetes (T2D) and lower risk of prostate cancer. Quantitative expression analysis has proven the risk allele for T2D is associated with higher level of JAZF1. On the other extreme, knockout mice of JAZF1 are more sensitive to insulin and resistant to fat induced obesity as well as diabetes. However, the animals have defects in mammary gland development. The lab is interested in 1) characterize the knock out animal for prostate and breast cancer risk. 2) study the function of JAZF1. 3) study the inverse correlation between T2D and prostate/breast cancers.