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Questions We Are Asking

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Question 1

Vascular Adventitia and Vascular Diseases

Vascular adventitia is an evolutionarily conserved structure down to organisms that have hemolymph (i.e. minimal pressure), highlighting its importance. Single cell characterization shows adventitia undergo huge changes in different vascular diseases. To date, no therapies target cellular changes in the adventitia. We want to understand (1) which cell(s) in the adventitia modify vascular diseases, (2) how do they do it, and (3) how can we modify the adventitia to target diseases?

Question 2

Epigenetic Contributions to Vascular Disease Propensities

99% of your genome does not encode for protein-coding genes. Much of these non-coding regions control cellular identities and disease-related responses through epigenetic modifications. The power of epigenetic influence on vascular diseases is best illustrated by the drastically different propensities of neighboring arterial segments to develop atherosclerosis, aneurysms, or other vascular pathologies. These fascinating observations also provide us with unique case-control studies on how epigenetics influences disease risk. We aim to understand (1) what determines the distinct epigenetics of  different cell type(s) within the vessel wall, and (2) how these epigenetic factors contribute to differential disease risk and (3) how these differences may be leveraged to treat or prevent vascular diseases. 

Question 3

Human Genetics to Cellular Mechanisms

Human genetics is a powerful way to discover new disease modifiers. Hundreds of human variants have been identified that alter risk of vascular diseases including atherosclerosis and aneurysms, but very few have ever been utilized to treat diseases due to our poor understanding of the cellular and molecular mechanisms that underlie each disease signal. We leverage multi-omic data that we generated from human tissues and cell cultures in combination with in vitro models and CRISPR screens to understand (1) which gene(s) are associated with each genetic signal, and (2) which cell(s) and biological processes do these genes act through and (3) how this information can be leveraged to develop novel theraputics. 

Question 4

Developmental Biology in Human Disease: Cellular Origins and Cell Fate Decisions in Disease

Vascular diseases are increasingly recognized to be influenced by cell-state and cell-fate transitions. Genes that influence cell-fate decisions alter disease risk and biology in the vessel wall. Humans, of course, are not heavily evolutionally selected for against age-related atherosclerotic diseases. Many pathological transitions are developmental and natural wound repair processes hijacked by environmental (i.e. tobacco, pollution, diet) or pathological (lipids, pressures) triggers.