Assigned mentee: Henrique de Assis L. Ribeiro (henrique.deassis@medicine.ufl.edu)
New U01 Awardee Presentation
Title: Multiscale modeling of wound healing
Abstract:
Chronic wounds are a major threat to public heath and the economy and present as a comorbid complication with major diseases in humans. Although the proper healing of cutaneous wounds requires collective and coordinated behaviors of multiple cell types, the rate-determining step is the recruitment and function of dermal fibroblasts, which are directed to invade the wound by a gradient in the concentration of platelet-derived growth factor (PDGF). A great deal is known about the signal transduction pathways activated by PDGF receptors and other receptor tyrosine kinases; yet mechanistic insights about how those pathways are spatially organized to bias the dynamics of the actin cytoskeleton and the directionality of cell migration are still emerging. A still larger fundamental gap lies in the integration of molecular, supramolecular, cellular, and tissue-level dynamics of wound healing, which span disparate time (seconds to weeks) and spatial (nm to cm) scales. To advance this field, we are developing a predictive, multiscale model of the proliferative phase of wound healing, incorporating 1) receptor-mediated signal transduction, 2) self-assembly of contractile actomyosin structures, 3) morphodynamics and statistics of cell migration, and 4) collective cell behavior in vivo. Our partnership combines expertise in experimental cell biology and biophysical modeling, and model development will be guided by new, quantitative measurements at every scale of biological abstraction.
Biosketch:
Jason Haugh, Professor of Chemical & Biomolecular Engineering, North Carolina State University
James Bear, Professor of Cell Biology and Physiology, Lineberger Comprehensive Cancer Center and School of Medicine, UNC-Chapel Hill
Timothy Elston, Professor of Pharmacology, School of Medicine, UNC-Chapel Hill