• 
• 
  Chuanxin Huang,PhD
  
  Post-Doctoral Fellow

The BCL6 protein is a master regulator of the immune system that plays a critical role in governing survival and differentiation of B-cells, T cells and macrophages. BCL6 controls formation of germinal centers in response to T-cell dependent antigens and is thus required for high-affinity maturation of antibodies and memory B cells. It also regulates the differentiation of Th2 cells and the secretion of chemokines by macrophages. In addition, deregulated BCL6 expression occur frequently in human B-cell lymphomas and constitutively expression of BCL6 can cause lymphoma, possibly through its ability to promote cell proliferation and survival to inhibit differentiation. From the mechanistic standpoint BCL6 functions as a transcription repressor through the recruitment the Co-repressors mediated by the BTB domain and RD2 domain respectively. In vitro studies have demonstrated that BTB represses the genes involving cell proliferation and survival, while RD2 regulates the genes involving differentiation. However, the actual action of these two domains to B cell development in vivo remains unknown. Interestingly, whether the BTB or RD2 domain controls the gene expression in T cells and macrophages in the similar manner to in B cells needs to be further determined. My research interest is to understand the transcriptional network controlled by BTB domain and RD2 domain and the specific contribution of two domains to the action spectrum of BCL6 during normal hematopoiesis and lymphomagenesis. To approach these questions, I will combine mice genetics, immune bio-assay, biochemistry and systematic biology.

We will engineer knock-in mice to express BCL6 containing point mutations that disrupt either the BTB domain or RD2 domain while leaving all other BCL6 and Co-repressor functions intact to determine the specific contribution of the BTB and RD2 domain-dependent repression to hematopoietic and immune system lineages. Meanwhile we use integrated gene expression profiling and genomic localization studies to determine the core genes or pathways controlled by BTB and RD2 in normal hematopoietic and immune system.

Through this study we hope to elucidate the biochemical and biological mechanism through which BCL6 coordinates the function of different tissues. This date will have clinical implications since BCL6 BTB domain inhibitor drugs are currently under evaluation for the treatment of lymphomas and leukemias.