Research Team Member
Roger Markwald
University of South Carolina-Charleston
The Co-PI is a developmental biologist with extensive experience in cardiovascular
cellular and molecular morphogenesis. He has contributed to the description of the
origin and mechanisms of cardiac cushion formation as well as studies on examining
genes expressed during both heart/cushion and limb development. Much of his work
has focused on the role of the extracellular matrix in embryonic cell
proliferation, migration and differentiation. His work includes the first studies
showing that a subset of cardiac endothelial cells acquire the potential to
transform into cushion mesenchyme in response to a multicomponent complex secreted
by the myocardium called adherons. The latter act as extracellular carriers for
growth factors of the TGF beta gene family, which specifically activate
endothelial transformation through BMP receptor 1b (Alk6) signaling. Recent
microarray studies in his laboratory have identified two fasciclin genes -
periostin and igH3 - which function as adhesive extracellular proteins that
promote remodeling of cushion mesenchyme into mature valve leaflets through
interactions with cell surface integrins and interplay with other matrix molecules
such as fibronectin, fibrillins, collagen, hyaluronan, proteoglycans. Changes in
the expression of periostin and igH3 correlate closely with changes in the
viscoelastic properties of cushions over time. Collaborative studies with
Dr. Forgacs and his team are in progress using genetically modified mice to
confirm that viscoelastic changes in cushions are mediated through periostin and
igH3 using tensiometric and interfacial surface tension assays. The Co-PI will
provide embryological and molecular expertise and will supply samples of cushion
and limb tissues from mice null for periostin or igH3. The Co-PI has developed in
vivo-like dynamic assays in which the role of biomechanical signaling (cyclical
stretch and sheer stress) upon regulation of periostin/ igH3 expression can be
studied in cushions undergoing valvulogenesis. He is interested in using
bioprinting as a means to extend these studies to include scaffolds seeded with
cells and growth factors.
