Lucchesi Lab

Lucchesi Laboratory

A key aspect of signal transduction is the ability of cells to translate an extracellular signal into an intracellular one, enabling cells to respond to their environment. The initial response of cells to growth factors and hormones is facilitated by interaction with cell surface receptors; this interaction then leads to the activation of intracellular signaling pathways. These pathways often require a series of sequential protein kinase reactions that ultimately regulate many cellular processes including growth, matrix production, contractility and ion transport.

Our interests concern the regulation of the kinase signaling pathways by neurohormonal agents and reactive oxygen species in the cardiovascular system. Utilizing both intact tissue and cell culture models, our laboratory has concentrated on elucidating the role that kinases may play in modulating ion transport, matrix remodeling, sarcomere assembly, and contractility and cell growth. Representative current projects include: (1) Role of oxidative and nitrosative stress in the pathogenesis of heart failure; (2) Altered matrix remodeling in pressure and volume-overload heart failure with particular emphasis on cardiac fibroblasts; (3) Regulation of vascular smooth muscle cell growth by hypertrophic and hyperplastic factors. (4) Regulation of vascular smooth muscle function by kinase signaling pathways in vivo using two model systems: A carotid artery wire injury model (growth) and resistance vessel preparations (contractility). A combination of antisense, adenoviral and transgenic technologies are used to downregulate and manipulate expression/activation of key components of signaling cascades. 5) Alterations in myocyte Ca2+ homeostasis and sarcomeric assembly in pressure vs. volume overload.

Nationwide Children's Hospital
700 Children's Drive Columbus, Ohio 43205 614.722.2000