Davy Vanhoutte, PhD

My research is focused on cardiac disease and inherited muscle disorders, including muscular dystrophies, and how the extracellular matrix (ECM) — the network of proteins surrounding and supporting cells — actively contributes to disease progression rather than serving as passive scaffolding. My laboratory studies the thrombospondin family of matricellular proteins, along with other ECM-associated proteins, as regulators of inflammation, fibrosis, proteostasis, and membrane stability, as well as fibroblast–muscle cell crosstalk in tissue homeostasis, injury, and repair. Building on these mechanistic insights, we are developing matrix-directed and gene therapy-based strategies to identify new therapeutic approaches for various muscular dystrophies and other cardiac and skeletal muscle disorders.

My research journey began with my doctoral work in Belgium at the University of Leuven, where I demonstrated that matricellular proteins and proteoglycans actively regulate leukocyte recruitment, matrix metalloproteinase activity, and collagen organization during heart disease — early evidence that ECM composition, rather than collagen content alone, determines functional cardiac remodeling. During my postdoctoral training with Dr. Jeffery Molkentin at Cincinnati Children's, I identified previously unrecognized intracellular functions of thrombospondin family proteins in striated muscle, establishing that ECM remodeling is not simply a downstream consequence of muscle and cardiac injury, but an active driver of disease progression.

Among my notable contributions, my work established that thrombospondin-4 promotes trafficking of membrane-stabilizing protein complexes, including integrins and components of the dystrophin-glycoprotein complex, to the sarcolemma, protecting against cardiac and dystrophic muscle disease. In contrast, thrombospondin-3 acts on this same trafficking pathway in the opposite direction, impairing it and promoting sarcolemmal instability and injury in the heart, while thrombospondin-1 drives proteostatic stress signaling that contributes to cardiac and skeletal muscle atrophy. More recently, my NIH-funded lab is investigating the ECM-regulated mechanisms of Ullrich Congenital Muscular Dystrophy.

I am honored to serve as Councilor of the American Society for Matrix Biology (2025–2028), co-chair their Communication and Outreach Committee, and to have co-founded the ASMB Scientific e-Symposia series. My recognitions include the D. Collen Award for Postdoctoral Biomedical Research in the USA from the Belgian American Educational Foundation and the Basic Science Young Investigator Award from the Heart Failure Association of the European Society of Cardiology.

I serve on the editorial boards of several internationally recognized scientific journals, including Matrix Biology and Matrix Biology Plus, and regularly review manuscripts across cardiovascular, skeletal muscle, and gene therapy fields. Mentoring trainees at all stages is a passion of mine, and I strive to foster a collaborative, curiosity-driven lab environment. I welcome inquiries from collaborators interested in ECM biology, fibroblast–muscle cell signaling, thrombospondin and matricellular protein biology, or matrix- and gene therapy-based approaches to heart and skeletal muscle disease.