We study the trafficking of white blood cells lymphocytes, dendritic cells, monocytes, etc. These events regulate immune responses by controlling the access of leukocytes to sites of inflammatory or immune reaction in the body. The vascular addressins and adhesion receptors control immune cell recruitment, and thus local immune and inflammatory responses.
We showed that adhesion receptors act coordinately with G protein-linked chemoattractant receptors in a multi-step process that controls the specificity and provides combinatorial diversity in leukocyte trafficking. A major focus of the group is on understanding the programming of targeted immune cell trafficking in homeostasis, in the immune response and in disease models colitis, psoriasis, EAE, cancer.
Genetic, antibody and small molecule-based approaches allow us to discover and define the mechanisms involved. The studies have fundamental implications for the therapeutic regulation of immune responses. Rationale: Pericytes are capillary mural cells playing a role in stabilizing newly formed blood vessels during development and tissue repair. Loss of pericytes has been described in several brain disorders, and genetically induced pericyte deficiency in the brain leads to increased macromolecular leakage across the blood-brain barrier BBB.
However, the molecular details of the endothelial response to pericyte deficiency remain elusive. Objective: To map the transcriptional changes in brain endothelial cells resulting from lack of pericyte contact at single-cell level, and to correlate them with regional heterogeneities in BBB function and vascular phenotype. We find that endothelial cells without pericyte contact retain a general BBB-specific gene expression profile, however, they acquire a venous-shifted molecular pattern and become transformed regarding the expression of numerous growth factors and regulatory proteins.
We also reveal heterogeneous modes of pericyte-deficient BBB impairment, where hotspot leakage sites display arteriolar-shifted identity and pinpoint putative BBB regulators. By testing the causal involvement of some of these using reverse genetics, we uncover a reinforcing role for angiopoietin 2 at the BBB.
