Aghi Laboratory

Dr. Aghi's research interests focus on the microenvironment of glioblastoma.  Scientists in Dr. Aghi's basic science laboratory are working to (1) define the role of circulating marrow-derived vascular progenitor cells in the formation of the abnormal microvasculature of glioblastomas; (2) determine how gliomas become evasive to anti-angiogenic treatments that have become increasingly used in glioblastoma treatment since the accelerated FDA approval of the anti-VEGF neutralizing antibody bevacizumab for glioblastoma treatment; (3) determine the impact of tumor mutations and cell signaling pathways in the sensitivity of human glioblastomas to anti-angiogenic treatment; and (4) determine the ability of hypoxia to upregulate autophagy as a cell survival mechanism in glioblastoma, the impact of mutations in this process, and whether autophagy might contribute to evasion to anti-angiogenic therapy.

Perivascular Progenitor Cells in Glioblastoma
Marrow-derived endothelial and perivascular progenitor cells give rise to tumor neovasculature in animal models, but the role in human glioblastomas remains undefined.  Using murine xenografts directly derived from human glioblastomas, the Aghi lab is working to uncover the role of vasculogenesis in human glioblastoma vascular development.  Specific objectives are to identify tumor-secreted factors that mediate the recruitment of perivascular progenitor cells to gliomas, and determining whether inhibiting these factors in conjunction with agents targeting the vasculature itself disrupts glioma growth.

tl_files/NS_Main/User/Lab_AghiM/murine MRI_small.jpgBevacizumab Evasion in Glioblastoma
VEGF-neutralizing antibody bevacizumab was recently FDA approved for recurrent glioblastoma but often causes infiltrative recurrences that are not amenable to existing treatments.  The Aghi lab is usuing human glioblastomas evasive to bevacizumab treatment to uncover mechanisms of evasion to bevacizumab.

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