What we do

We model brain vascular pathologies across the cognitive health-span

With a commitment to discovery of impactful treatments for dementia-causing diseases, we use clinical insights to design laboratory experiments that uncover molecular connections between brain vascular disease and brain degeneration.

Our mission is to put an end to dementia

With recent technological advancements, we are shifting from clinical descriptions of dementia toward understanding the molecular underpinnings of early disease, opening the door to the development of game-changing treatments.

Our team works on biomarker discovery for the development of treatments against dementia. We are especially focused on blood molecular biomarkers for vascular causes of dementia and identification of druggable targets for impactful clinical trials.

How we approach discovery—multi-modal modeling

To develop treatments, new approaches to discovery are needed. Our team operates at the juncture of preclinical and clinical research to understand dysfunction of brain barriers (vasculature) in dementia-causing diseases. We measure molecular vascular contributions to cognitive impairment and dementia (VCID) in living humans. We use brain tissue, blood, cerebrospinal fluid, a variety of imaging, clinical phenotypes, and advanced data analytics to identify blood signatures of disease and develop biomarkers for early detection and therapeutic interventions.  

We envision a future without dementia

Our goal is to develop molecular measurements for the screening of early disease and implementation of preventative treatments—similar to cholesterol-lowering medications that prevent heart disease, we will one day measure brain health routinely and modify risk of brain degeneration before symptom onset.

Projects

Disease proteomic signatures in blood—early detection to save the brain

We measure molecules in fluid biological samples and brain tissue for the detection of disease signatures and the development of non-invasive biomarkers of VCID across the brain’s lifespan and across neurodegenerative disease phenotypes. Combining clinical signs and symptoms with molecular indices of disease is needed for early detection and treatment of pathology before irreversible damage and dementia.

CADASIL-centered modeling of vascular brain dysfunction

The goal of this project is to build the best in vitro model of vascular degenerative brain disease for mechanistic understanding and drug screening. We combine clinical data with molecular measures to identify clinically-relevant molecular abnormalities. We then use experimental models built from patient-derived stem cells to test the mechanistic relationships of molecular abnormalities. This approach provides novel diagnostic molecular biomarkers that could be implemented in clinical trials and builds a platform for personalized medicine and drug screening to identify impactful treatments.

Liquid biopsy of abnormal brain barriers and dysfunctional neurovascular unit

We are dissecting vascular contributions to brain degeneration down to cellular and molecular effects by using extracellular vesicles (EV) as a liquid biopsy approach. Cell-specific EV molecular quantifications represent a novel approach to biomarker quantification. We are currently performing proteomics and other molecular omics quantifications from vascular cell-derived EVs for discovery of VCID-associated molecular signatures. In parallel we are working on improving the process of cell-specific EV isolation, with emphasis on technical reliability. Here our goal is to turn discoveries into reliable biomarkers by developing isolation approaches that do not require technical expertise and can be used by all.

Dysregulated angiogenesis in dementia—a story of brain barriers and inflammation

In parallel with unbiased discovery projects, we are testing the relevance of druggable vascular targets, such as pathological angiogenesis, in brain degenerative diseases. Our models have shown that dysregulations in angiogenesis and blood-brain barrier dysfunction are correlated with slowed processing speed and executive dysfunction. We are improving these models with the goal of identifying therapeutic opportunities. In addition, we are building in vitro experimental read-outs for these pathologies with the goal of identifying molecular interventions that could preserve brain health.

Defying genetic predetermination—modeling resilience

What makes some brains susceptible to dementia while others grow old without cognitive impairment? By studying individuals who defy predictive models, we seek to uncover the molecular underpinnings of resilience that boost the brain’s ability to resist pathology and maintain function. We are especially focused on understanding resistance in people with confirmed mutations in NOTCH3 (e.g. our CADASIL study) and resilience in super-agers who have defied the most significant risk for dementia — age!

Diseases we tackle

By developing tools and approaches that capture blood vessel disease and its links to brain dysfunction, we hope to make breakthrough discoveries that will help those at risk for or living with CADASIL, Alzheimer’s disease, Lewy body disease, frontotemporal dementias, and other neurodegenerative diseases with dysfunctions of blood vessels. Learn more about participating in one of our clinical studies.

  • NOTCH3 mutations & CADASIL

  • APOE4 carriers ± Alzheimer’s disease & frontotemporal dementias

  • White matter disease on MRI