Research Projects

Dendritic cells (DCs) are antigen-presenting cells that develop from a multipotent hematopoietic progenitor in bone marrow and facilitate immune surveillance. They can be categorized into conventional DCs (cDCs), plasmacytoid DCs (pDCs), and monocyte derived DCs (moDCs) subsets. The development and function of DC subsets are based on temporal gene expression regulation. The Cohesin complex, a multiprotein complex within the nucleus, has been implicated in shaping genomic interactions that induce the expression of cell-type-specific genes. Mutations in Cohesin complex subunits have been associated with myeloid malignancies, and DC deficiency facilitates myeloproliferation. To determine the role of the Cohesin complex in DCs' development and function, researchers have developed two mouse strains with Cohesin-deficient DCs. Preliminary data suggests that deletion of Cohesin complex subunits in DCs promotes the deficiency of cDCs in lymphoid organs. Based on the critical role of Cohesin complex in the dynamic transcription of cell-type-specific genes, the researchers hypothesize that Cohesin might be playing a role in DCs' development through regulation of genome organization and expression of transcription factors required for DCs' differentiation. The study will involve comprehensive immuno-phenotyping of mouse strains, comparing the transcriptome of wild-type and Cohesin-deficient DCs, and understanding the contribution of Cohesin loss in DCs in inducing leukemogenesis.