Chemotherapy-induced nausea negatively impacts quality of life, can alter adherence to chemotherapeutic treatment plans, and is repeatedly ranked as the greatest fear by patients beginning cancer treatment. The goal of this project is to better understand the sensory systems and molecular mechanisms involved in detection of stimuli leading to generation of nausea. We hope to define a molecularly unexplored sensory circuit and its role in modulating organism behavior and physiology. The most efficacious anti-nausea medication class target serotonin receptors preferentially expressed in the sensory component of the vagus nerve. However, the anatomical distribution of innervation by these fibers remains unknown, as does the effect of manipulating this circuitry on behavior. I will use genetic tools including mouse transgenic lines and adenoviral vector gene delivery to specifically map the anatomy and functionally manipulate candidate nausea circuits. Examination of this system will open basic research into a poorly characterized and clinically relevant sensory system, and also provide potential alternative targets for therapeutic intervention of high relevance to many patients.
Chemotherapy-induced nausea is a devastating side-effect that alters patients'medical course and contributes to substantial morbidity and mortality. The goal of this project is to explore the sensory systems that mediate the detection of noxious stimuli and development of nausea. We aim to gain better appreciation of this poorly defined sensory system so that we can suggest alternative strategies for therapeutic intervention.
| Lou, Shan; Adam, Yoav; Weinstein, Eli N et al. (2016) Genetically Targeted All-Optical Electrophysiology with a Transgenic Cre-Dependent Optopatch Mouse. J Neurosci 36:11059-11073 |
| Williams, Erika K; Chang, Rui B; Strochlic, David E et al. (2016) Sensory Neurons that Detect Stretch and Nutrients in the Digestive System. Cell 166:209-21 |
