The long-term research goals of John R. Henley, Ph.D., are to determine how cues in the microenvironment guide neural cell migration processes, the role of dysfunctional guidance mechanisms in disease and how to control chemotactic migration for therapeutic purposes.
Dr. Henley's lab utilizes cell biology, biochemistry, genetics, molecular biology and behavioral research. These approaches help to define the individual spatiotemporal signal transduction mechanisms by which the nerve growth cone at the tip of elongating axons detects extracellular guidance cues and dynamically regulates cellular effectors to control the direction of axon extension.
Cellular migration guided by extracellular cues in the microenvironment (chemotaxis) is a critical driver of embryonic development, wound healing and regeneration. It is also the pathogenesis underlying cancer invasion and metastasis. Numerous guidance cues and their cognate receptors have been identified in the nervous system. However, the downstream signal transduction events that polarize effector processes in the cell and mediate chemotactic migration remain largely unknown.
Recent advances of this National Institutes of Health-funded work provide molecular insights into how guidance cues elicit local Ca2+ and phosphoinositide signals in the growth cone. This, in turn, directs vesicle trafficking and polarizes the distribution of integrin-based substrate adhesions during chemotactic guidance in the developing nervous system.
- Transduction mechanisms mediated by nerve growth cone guidance
- Pathways controlling regeneration in the brain and spinal cord
- Mechanisms underlying invasion of glioblastoma multiforme
Significance to patient care
These projects demonstrate how modulating the activation state of integrin receptors can support axon regeneration, and how cues in the microenvironment drive the highly invasive nature of high-grade malignant brain tumors. The underlying premise is that a better understanding of how specific signaling pathways polarize effector processes to drive migration will point the way toward pharmacotherapeutic interventions to treat significant clinical problems. These include autism spectrum disorders, lack of regeneration in the nervous system and invasive brain tumors.