Myeloid lineage in Gliomas

Claudia Han
Appointment Period: 2016-2018, Grant Year: [31]

Microglia are the resident macrophages of the brain. Despite sharing common properties with other tissue resident macrophages, microglia have specialized functions, unique to the central nervous system, such as synaptic pruning and clearance of protein aggregates. These differences are reflected on the genomic level as microglia and other tissue resident macrophages possess mRNAs and enhancers exclusive to themselves. Interestingly, macrophage epigenomic and transcriptomic profiles are lost, and new ones gained, following a change in environment or tissue locality, suggesting that environmental factors influence the specific tissue macrophage identity. Recently, we identified MLXIPL as a potential transcription factor whose expression is upregulated in microglia progenitors upon migration into the brain, suggesting that MLXIPL contributes to microglia identity. The major goals of my research will be to determine the roles of MLXIPL in specifying microglia functions in normal brain homeostasis and in Glioblastoma Multiforme (GBM) using next generation sequencing methods. One major direction will be to investigate the consequences of deletion of Mlxipl on microglia gene expression and epigenetic landscapes in the normal mouse brain and a mouse model of GBM. In parallel, I will determine the epigenomic landscapes and transcriptomes of microglia and macrophages in human Glioblastoma tissue obtained from human subjects. By integrating the findings from these two complementary systems I hope to be able to identify transcription factors and regulatory pathways that may provide new therapeutic targets.

PUBLICATIONS (resulting from this training)

Trainee recently appointed to grant, publications are still in progress.