Somatosensory Circuit Assembly
There is an incredible diversity to the sensations that we experience. While these signals can be encoded by receptors and channels in the nerves at your fingertip, they must be properly integrated to generate complex sensory perceptions, like the relief of itch by scratching or pleasure from a gentle touch. However, they can also be transformed into debilitating forms of allodynia, or “other pain,” following nerve damage.
We study how different types of neurons encoding distinct somatosensory modalities are assembled into functional circuits. To do this, we combine transcriptomic approaches with CRISPR-Cas9 genome editing to identify molecules that regulate synaptic wiring of sensory neurons into the brain and spinal cord to understand how alterations in these circuits impact sensory behaviors. We focus on molecules that are implicated in neurodevelopmental disorders with somatosensory processing defects and on wiring mechanisms that go awry in the development of chronic pain.
Human Tissue for Preclinical Pain Research
The ultimate goal of our research is to help patients suffering from chronic pain and other somatosensory disorders. To do this, we have developed complementary approaches to understand how different signaling molecules, cell types, and circuit functions are conserved between model organisms and humans. Here we use human nervous system tissue from organ donors and surgical patients to profile the functional, transcriptomic, and morphological properties of human neurons from healthy patients and people suffering from chronic pain.
Optical and Genetic Tool Development
Oftentimes we have had a research direction run headlong into a wall and have been forced to wait (impatiently) for the development of a new approach or technique. In anticipation of this, we work in parallel to develop new optical and genetic tools to answer key biological questions. Current efforts are now focused on photoswitchable multichannel control of GPCR signaling pathways and towards synapse-specific optical modulation of synaptic transmission and circuit tracing.