Epigenetic signatures and association with hemorrhage and high risk features in brain arteriovenous malformation

Brain arteriovenous malformations (bAVMs) are an important cause of intracranial hemorrhage (ICH) in young adults. Treatment is invasive and controversy remains over the clinical management of unruptured bAVMs. Robust prognostic and monitoring biomarkers are completely lacking, which are critically needed for future clinical trials of anti-angiogenic or anti-inflammatory therapies. Emerging data suggests that epigenetic mechanisms, such as DNA methylation regulating gene expression, play a role in cerebrovascular disease, yet comprehensive epigenomic studies in bAVM have not been performed. Blood epigenetic profiling poses a novel direction to identify epigenetic signatures that differentiate those at risk for ICH. 

In this project, we are utilizing whole methylome sequencing and methylome arrays to identify blood epigenetic signatures in bAVM patients that reveal novel prognostic or monitoring biomarkers (genes) and point to new therapeutic targets for hemorrhage and high risk features.  Using this approach, we are also studying whether blood epigenetic signatures can be used to differentiate bAVMs that harbor somatic mutations. These studies capitalize on the large UCSF Brain AVM Project cohort (PI: Helen Kim) with detailed clinical and genetic data and banked specimens which began in 2000.