Medical Physics

Biography

Biography: Sarah S Knox

Abstract

The strong focus on genetics in carcinogenesis research has somewhat obscured the important role of the microenvironment in regulating gene expression and controlling mutations. The membranes of all cells and mitochondria contain multiple ion channels that create a voltage gradient across the cell membrane, and combined with gap junctional currents create endogenous bioelectrical fields. These fields have long range effects on physiological functioning. Extensive research into multiple aspects of this bioelectric signaling system indicates that they play an important role in development, cell cycle progression, differentiation, migration and apoptosis; and interact with epigenetic mechanisms to influence gene expression. Depolarization (a prerequisite for the epithelial mesenchymal transition initiating tumor formation) has also been experimentally demonstrated to initiate mutagenic cell behavior in the absence of any primary tumor or genetic mutation. The current ‘targeted’ treatment modalities aim to bioengineer specific parts of signaling systems (e.g. kinases), but even in the most successful cases, inevitably perturb other, unintended components, having unintended consequences. Preliminary work on limb regeneration in frogs (the Levin lab) has demonstrated that an appropriate bioelectric signal can activate an entire subroutine to initiate limb regeneration, without micromanaging individual components. Implications for cancer therapeutics will be discussed.