The overall goal of Dr. Lu's laboratory is to investigate the mechanism of epigenetic control. We would identify novel mechanisms that regulate histone methylation and investigate the siginificance of these controls in transcriptional re-programming during the conversion of somatic cells to pluripotent stem cells (iPS)cells. The key problems we intend to resolve is how the major methylation at histone H3 K4, K9 and K27 are regulated during re-programming and how these changes are responsible for turning off the somatic histone codes and turning on the stem cell-specific codes. Our finding that major components of histone methyltransferases, such as WDR5, RBBP5, and EED may also serve as subunits of CUL4-DDB1-RBX1 ubiquitin E3 ligases to regulate histone methylation by ubiquitin-dependent proteolysis. Since the CUL4-DDB1-dependent mechanisms for H3K4 or H3K9, and K27 methylation may profoundly regulate the epigenetic control of gene expression, it is critical to investigate and identify these mechanisms to understand how epigenetic regulation is achieved in response to various signals.

Dr. Lu's laboratory has established strong and innovative research foundation for these investigations and is applying advanced technologies in proteomics and molecular genetics to identify the differences between normal and cancer cells and to establish pre-clinical disease models for mechanistic insights and for developing therapeutic strategies. Dr. Lu's laboratory is also actively developing approaches to translate these new findings to clinically useful applications for cancer diagnosis and treatment.