Our Research

We are passionate about combining our unique access to the human brain with emerging genomic and translational technologies to re-envision and advance cerebrovascular medicine.

Topics

Scientific diagram illustrating blood vessel development, muscle formation, and cell differentiation, including labeled graphics of fibroblast, pericyte, endothelial cells, and smooth muscle, with accompanying illustrations of cellular processes and microscopy images.

Cell-specific genomic contributors to human vascular malformations

Using single-cell genomics and spatial transcriptomics, we recently assembled a cell-resolution molecular map of the human brain’s vasculature. By applying this approach to human arteriovenous malformations (AVMs), we discovered molecular hallmarks of abnormal vascular patterning and cellular contributors to hemorrhagic stroke. We are now investigating the upstream regulatory mechanisms which cause vascular malformations to form or progress and developing cell-specific precision therapeutics to prevent AVMs from bleeding.

Microscopic two-color image, left side showing a network of green glowing filaments, right side showing a multicolored vertical structure with yellow, purple, and blue hues.

Functional genomics & regenerative vascular cell engineering to restructure the cerebrovasculature

Depletion of cerebrovascular support cells, known as mural cells, results in fragility and hemorrhagic stroke. However, there are no means to replenish these cell populations. Using induced pluripotent stem cells (iPSCs) and vascular organoids, we are now engineering the cerebrovasculature in vitro to investigate mechanisms of mural cell depletion with functional genomics and to devise means of cell-based replenishment to stabilize the diseased vasculature.    

Diagram of the brain showing blood vessels involved in a stroke, including the Sylvian vein, MCA, ICA, and AVM. Insets show detailed views of a catheter inserting into blood vessels, with labels indicating biopsy coil, white blood cells, endothelial cells, and blood vessels.

Non-invasive human cerebrovascular molecular profiling

Vascular malformations and aneurysms are not amenable to traditional biopsies.  To translate our genomics approaches, we recently developed a new technology to extract and molecularly profile brain endothelial cells in patients without the need for surgery, called endoluminal biopsy. Using this technology, we are now studying molecular attributes of the human cerebrovasculature in vivo. We are also investigating the molecular heterogeneity of arteriovenous malformations and aneurysms to re-classify them biologically and explain differences in behavior or response to precision-based therapeutics.  

Illustration of human head with overlapping waves, lines, and glowing red and orange light beams radiating from the brain area, suggesting brain activity or neural signals.

Enhanced delivery of brain therapeutics

The blood-brain barrier (BBB) is a unique property of the cerebrovasculature and tightly regulates molecular and cellular exchanges between the brain and circulation. While the BBB is needed for brain homeostasis, it serves as a perpetual obstacle for delivering brain therapeutics. Focused ultrasound is an emerging non-invasive technology to selectively disrupt the BBB to enhance delivery of therapeutics to the brain. Using novel primary tissue and organoid models, we are now investigating how to harness this technology and viral capsid enginerring to deliver next generation vascular- and brain-targeted therapeutics.