Sidharth Tyagi, MD, PhD

Dr. Sidharth Tyagi’s research focuses on how ion channels regulate pain signaling and how these proteins can be targeted to develop more effective, non-opioid treatments. He leads a research group in Yale’s Department of Anesthesiology that combines ion channel physiology, protein engineering, and human sensory-neuron models to connect fundamental mechanisms with therapeutic development.

A central focus of his laboratory is targeted protein degradation: designing molecular tools that recruit the cell’s own machinery to remove disease-relevant ion channels. His group is investigating this approach for voltage-gated sodium channels, including NaV1.7 and NaV1.8, which play critical roles in the electrical activity of pain-sensing neurons. The goal is to establish whether selectively reducing channel abundance can provide durable suppression of pathological excitability.

His laboratory also studies how sodium channels work together to shape neuronal firing and how their delivery to, and removal from, the cell surface influences pain signaling. By integrating electrophysiology, quantitative imaging, and human stem cell–derived sensory neurons, the group aims to identify therapeutic strategies that may be overlooked when channels are studied individually or outside their cellular context. Complementary projects examine how existing drugs interact with sodium channels and how these interactions might improve local anesthesia and pain treatment.

As an anesthesiologist-scientist, Dr. Tyagi’s long-term goal is to translate mechanistic discoveries into therapies that address unmet needs in pain medicine.