The Aghi Lab


The Research

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.

Perivascular invasion in a xenograft in a bevacizumab resistant xenograft
Immunofluorescent staining of a human to murine xenograft shows tumor cells (blue) invading brain parenchyma (green) in a perivascular (blood vessels red) manner.

Upregulated gene categories in bevacizumab evasive glioma (BEG)
The genes that were upregulated were from anti-angiogenic, cytoskeletal, pro-invasive, cell-cyle, and immune system genes. The Aghi lab is working to further characterize these genes.

Bevacizumab 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 using human glioblastomas evasive to bevacizumab treatment to uncover mechanisms of evasion to bevacizumab.

BLC3 expression in response to hypoxia
After 24 hours of hypoxia, cells transduced to express an LC3-GFP fusion protein exhibited more punctate green fluorescent staining, consistent with autophagy.  This green punctate staining decreased after treatment with autophagy inhibitor 3-MA, but remained high after treatment with autophagy inhibitor BafilomycinA1. 


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The Manish K. Aghi Lab at the University of California, San Francisco

The Helen Diller Family Cancer Research Building

1450 3rd Street

Room HD-410

San Francisco, CA 94158