Schwann cell growth factor signaling pathways
The proliferation of Schwann cells during development is stimulated by growth factors of the neuregulin family that are associated with axonal membranes of peripheral nerve fibers. We characterized neuregulins synthesized by embryonic sensory neurons and identified several novel isoforms with distinct mechanisms for membrane association and processing. Schwann cell division is dependent on stimulation with both neuregulin and an agent that elevates intracellular cAMP. We have shown that neuregulins and cAMP synergistically stimulate expression of cyclin D3 in Schwann cells, which is required for progression from G1 to S phase of the cell cycle. We are investigating the signaling mechanisms that regulate cyclin D expression and Schwann cell proliferation. The ultimate goal of these studies of Schwann cell regulation is to facilitate the development of new therapies for peripheral neuropathies as well as nerve regeneration after injury.
Pathophysiology of Abdominal Aortic Aneurysm
We are investigating the pathophysiology of abdominal aortic aneurysm (AAA) with the goal of developing improved methods to diagnose the disease and strategies for medical treatment of patients to slow AAA expansion. One aspect of this work is based on the use of an animal model of AAA. Microarray expression analysis identified a number of genes related to immune function and inflammation that are upregulated in AAA tissue, consistent with a role for inflammation in AAA formation. Consistent with this, we showed that drugs that block specific pro-inflammatory targets significantly inhibit aneurysm expansion. Microarray analysis of human tissue also identified AAA-specific gene expression profiles. Current research is aimed at further study of AAA gene expression and the development of novel diagnostic and therapeutic approaches.
Figure 1. Schwann cells plated on dishes coated with the N-terminal non-collagenous domain of alpha4(V) collagen spread and form focal adhesions that contain vinculin (left) and phosphotyrosine (right).
