The Stiles laboratory studies basic principles of growth factor signal transduction in nerve cells and in the developing nervous system. Two examples of work in progress are as follows:
Growth Factor signal transduction through long axons.
In myelinated nerve cells, target-derived neurotrophins must communicate with a nucleus that can be more than a meter away. In collaboration with Dr. Rosalind Segal (Dept. of Pediatric Oncology, DFCI) we are learning how target-derived neurotrophins transmit information through long nerve axons.
Regulation of Neuronal Development by Platelet-Derived Growth Factor.
Neurons, oligodendrocytes and astrocytes in the central nervous system are thought to be derived from a pluripotential stem cell in the embryonic neural plate. Our laboratory has shown that uncommitted stem cells from the developing cortex of embryonic rats develop into neurons following exposure to platelet-derived growth factor (PDGF). The laboratory is using adenoviral vectors to probe the signal transduction pathways that regulate this PDGF-mediated developmental switch. In addition, we are using subtractive hybridization methods to isolate PDGF-responsive gene sequences from the uncommitted stem cells.