Biomedical Sciences Graduate Program(s)
Biomedical Sciences Graduate Programs
Computational Modeling of Tissue Patterning:
Our laboratory develops computational models to study how cellular behaviors and molecular signals within complex biological systems regulate tissue patterning events, such as blood vessel growth and embryogenesis. These models integrate the behaviors of thousands of interacting cells, growth factor signaling proteins, and epigenetic stimuli to predict tissue patterning events during physiological tissue assembly and pathological tissue remodeling. Combinations of molecular mechanisms, mechanical forces, and progenitor cellular behaviors lead to emergent simulated tissue morphogenesis, such as the growth of a new vascular bed into a nutrient-deprived tissue. The results of these computational simulations are compared to analogous (but entirely independent) in vivo experimental results. The outcome contributes to the understanding of how multiple factors, or potential drug targets, affect, for example, the growth of new coronary blood vessels in a diseased heart. Because this multi-scale computational approach rationally integrates genomic and proteomic data with cellular behaviors and tissue growth, the long term goal is to enable faster and more effective drug discovery and improve tissue engineering techniques.
Human progenitor cells as therapeutic targets for tissue engineering:
Vascular growth and remodeling in adult mammals involves numerous cell types and cellular behaviors, and is critical for adaptation to exercise, therapeutic revascularization of ischemic tissues, and tissue engineering. A growing body of literature suggests that human adipose-derived cells possess previously unrecognized developmental plasticity, in vitro and in vivo. In collaboration with Dr. Adam Katz (UVa Plastic Surgery Dept.), we investigate the capacity for human adipose-derived progenitor cells to behave as perivascular support cells, their contribution to in vivo remodeling, and their therapeutic potential in revascularization. To this end, our studies characterize their structural and morphological interactions with microvessels, their proliferative activity, and their phenotypic changes in the in vivo tissue environment. This data allows us to further determine their effects on microvascular growth, maintenance, and capillary permeability. Since human adipose-derived cells are readily available, characterization of their behavior may yield novel therapeutic approaches to many vascular diseases as well as knowledge of how perivascular support cells, in general, participate in microvascular remodeling.
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 vs. venules in rat tissues. Using the differential expression of this marker and the expression of other vascular-specific markers, our lab tries to understand the signals responsible for conferring an artery or vein phenotype to new and pre-existing vessels and maintaining that phenotype as the tissue undergoes adaptation and growth.
Murfee WL, Skalak TC, & SM Peirce. (In press) Differential Arterial/Venous Expression of NG2 Proteoglycan in Perivascular Cells Along Microvessels: Identifying a Venule-Specific Phenotype. Microcirculation (Cover Illustration)
Longo, DM, Peirce, SM, Skalak, TC, Marsden M, Davidson LA, Dzamba BJ, & DeSimone DW. (2004) Computational Automata Simulation of Blastocoel Roof Thinning In the Xenopus laevis Embryo. Developmental Biology. 271: 210-222.
Peirce SM, Van Gieson EJ, & Skalak TC. (2004) Multicellular Simulation Predicts Microvascular Patterning and In Silico Tissue Assembly. FASEB Journal.10.1096/fj.03-0933fje. (Cover Illustration)
Peirce SM, Price RJ, & Skalak TC. (2003) Spatial and Temporal Guidance of Angiogenesis and Arterialization. American Journal of Physiology-Heart & Circulatory Physiology. 286: H918-H925.
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