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Research Project by Bryan Richardson

The focus of my research in the Johnson Lab is to generate a human model of cerebral cavernous malformation (CCM). CCM can either be inherited or can occur from spontaneous mutations in Krit (CCM1), OSM (CCM2), or PDCD10 (CCM3). While the disease is somewhat rare (1 in every 200 people), its manifestations range from headache to stroke. The disease is mainly found in the brain where lesions of “leaky” blood vessels accrue until a hemorrhage occurs. The main treatment option for CCM patients is invasive surgery. Most current research into CCM has relied upon ablation of different CCM genes in the mouse. My research project will involve the use of CCM patient derived endothelial cells. I will begin by optimizing a model for temporarily immortalizing CCM patient cells, while retaining their endothelial cell potential. Specific CCM mutations with in these cells will be identified and they will be studied for their ability to undergo angiogenesis both in vitro and in vivo. The development of this model will result in an ability to test different bone fide human CCM mutations from highly different genetic backgrounds for responses to therapeutic screening. Legend for figures below:: In vitro tube formation assay as a model for angiogenesis to study CCM.


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