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The objective of the McGuigan lab is to design predictive heterogeneous tissue mimetic systems for understanding mechanisms of tissue assembly and disease and to use these systems to identify therapeutic strategies to improve human health.
Drug discovery is slow, expensive, and often candidate compounds fail late in the development pipeline after significant resource investment. Failure occurs due to high toxicity in off-target tissues or lack of efficacy due to limited understanding of underlying mechanisms and variation in patient populations. Early identification of failure is difficult because cell behaviour in standard 2D plastic experimental systems is often not predictive of in vivo response. This is because cell behaviour is determined by a combination of intrinsic molecular properties and the local microenvironment, which in a tissue is complex and heterogeneous: tissues are composed of multiple cell types and matrix proteins organized into specific architectures. It is therefore not surprising that homogenous cell populations cultured in monolayers on the surface of plastic dishes, a microenvironment that has little resemblance to that in vivo, often fail to produce data predictive of cellular response in humans.
Physiologically relevant, personalized, tissue mimetic systems offer the opportunity to systematically dissect fundamental mechanisms of tissue assembly and disease to allow identification of novel therapy targets to manipulate these processes for therapeutic benefit. Furthermore, such systems offer the potential to classify the effectiveness of drugs in specific patients for the design of personalized therapies. Our mission in the McGuigan lab is to use tissue engineering strategies to assemble multicellular tissue mimetic platforms that are both physiologically relevant and allow acquisition of high value data for both drug discovery and fundamental research. Our research team is focused on understanding how to generate relevant tissue architectures that enable isolation of predictive data from specific cell populations within heterogeneous tissue systems.
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