Synthetic Control of Cell Signaling
Our lab, in close collaboration with Dr. Michael Caterina’s group, is developing genetically-encoded systems that force the movement of specific target proteins to different locations in the cell in response to specific extracellular signals, with the goal of optimizing these systems as (i) tools for the in vivo interrogation of signal transduction pathways and (ii) genetically-encoded therapies for widespread, persistent diseases, especially chronic pain.
1. One arm of this project involves the invention and optimization of systems that drive the extracellular signal-induced movement of proteins (a) from the nucleus to the cytoplasm, and (b) from the cytoplasm to the inner leaflet of the plasma membrane. While basic architecture of these systems has already been invented, optimization and elaboration of these systems is still underway.
2. The second arm of this project involves the coupling of signal-responsive translocation systems to inhibitors and activators of specific intracellular signaling pathways. At present, these efforts are focussed on developing signal-responsive inhibitors and activators of signaling via (a) Ras, (b) cAMP, and (c) intracellular calcium.
3. The third arm of this project is to interrogate the in vivo efficacy of these systems for rewiring signaling pathways (a) in sensory neurons, as a way to treat chronic pain, and (b) in hepatocytes, as a way to treat diabetes.