Ricardo Romo, Dallin Wassmer, Ben Young

The use of stem cells is fast advancing regenerative therapies. To fulfill the promise of regenerative medicine it is required that we understand fully both the stem cell and the endpoint tissue we aim to regenerate. Cells have three sources of energy: chemical, electrical, and mechanical. We know a fair amount about the first two, and very little about the third. The study of mechanical transduction is difficult because the stimulus at the site of a transducer is generally unknown. It is now evident that biomechanical stimuli are as crucial for regulating stem cell behavior as biochemical stimuli. In the case of degenerative diseases, recent advanced therapies promise to slowdown/stop progression, but there is no evidence brain health can be restored. In our laboratory, using a regenerative model, fresh water Planaria, we identified that cell-cell contact and concomitant mechanotransduction, mediated by the membrane protein occludin (OCLN), is one important stimulus during brain regeneration. The discovery of homology between the planarian and the mammalian CNS opens a door to examine parallels in regeneration and plasticity. Thus, it will be essential to understand how brain regeneration is controlled by mechanical transduction. Brain regeneration is under the control of biochemical stimuli through the Hedgehog signal transduction pathway. We aim to compare the effects of biomechanical stimuli of OCLN and biochemical stimuli of Hedgehog pathway during Planaria brain regeneration. Our laboratory is in a unique position to expand our knowledge of brain regeneration and plasticity, and provide new tools and evidence to better understand mechanobiology.