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The overarching goals of our research are to: 1) understand how tissues, or collections of biological cells and their extracellular matrix environment, grow and adapt in response to physiological and pathological environmental stimuli, and 2) use this information to develop therapeutic strategies for invoking/promoting tissue regeneration and repair. We are predominantly interested in pursuing these goals within the context of the adult microvascular system, which is essential in many human diseases, including heart disease, cancer, and chronic wounds. All of our projects combine multi-cell computational modeling with experimental analyses (see "About Us").
Specifically, we have on-going projects in the following areas:
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Chronic wounds, such as diabetic wounds, are a major global health and economic burden. Many such wounds fail to heal despite adequate implementation of existing treatment strategies. We are currently investigating the potential for human adipose progenitor cells (ASCs), which are derived from fat tissue collected during routine liposuction procedures, as a novel treatment strategy for diabetic wounds. ASCs offer many potential advantages over other progenitor cell types: they are relatively easy to harvest from adults in large quantities, adipose tissue is abundant in most people and readily accessible, and the harvest procedure is minimally invasive. Recognizing the shortcomings of existing biological products, we are developing an ASC-based wound care technology in collaboration with Dr. Adam Katz.
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A growing body of literature suggests that human adipose-derived cells (hASCs) possess previously unrecognized developmental plasticity. In collaboration with Dr. Adam Katz, we are researching the capacity for hASCs, when injected therapeutically, to contribute to microvascular growth in instances of tissue injury/disease. By using a combination of multi-cell computer models, in vitro assays, and in vivo experiments, we are determining the cellular and molecular mechanisms that regulate their observed therapeutic benefit in inducing microvascular growth and remodeling.
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The arterial and venous components of the circulation differ fundamentally in physiological function, cellular composition, and flow dynamics. Identifying the cell phenotypes associated with arterial/venous (A/V) determination is critical for understanding how the circulation develops, matures, functions to deliver blood to and from the tissues, and adapts to pathological stimuli. Recently, the discovery of A/V phenotypic markers has provided insight into vascular tree development and microvascular remodeling in the adult. We have identified a proteoglycan that is differentially expressed in arterioles and venules. Using the differential expression of this marker and the expression of other vascular-specific markers, our research aims to understand the signals responsible for conferring an artery or vein phenotype to new and pre-existing vessels and regulating that phenotype as the tissue undergoes pathological stimulation.
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Advanced atherosclerotic plaques contain microvessels extending into the shoulder region of the cap, and it has been hypothesized that these small vessels provide an additional route for leukocyte infiltration and propagation/expansion of the inflammatory environment within the plaque. However, the relative contribution of lumenally-derived leukocytes versus microcirculation-derived leukocytes in an advanced plaque has never been assessed in vivo because of technical limitations in dynamic cell lineage tracking. Agent-based computational modeling (ABM) provides a unique tool that is ideally suited to address this problem. We are developing and validating, through experimental analysis of histological tissues, a multi-cell ABM of an atherosclerotic plaque to test the hypothesis that plaque microvasculature serves as a significant conduit for leukocyte infiltration in advanced atherosclerosis.
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