Research Information
Research Interests
Dr. Yu earned a B.S. in both biology and physics from Tsinghua University. He earned a Ph.D. in molecular, cellular, and biophysical studies from Columbia University working in the lab of Lorna Role studying nicotinic receptor ion channels. He discovered the joy of recording electrical signals from cells and built his own electrophysiology rig from scratch, mesmerized as he watched neurons respond to different stimuli. Until beginning his postdoctoral fellowship in 1996, work on a collaborative project with Role and Richard Axel, he hadn’t yet been interested in genetics and molecular biology. A discussion about the “molecular shenanigans” Axel employed to remove cell types from the nervous system by deleting certain transcription factors inspired Yu to pick up molecular genetic tools and combine them with electrophysiology and optical imaging to explore the neurobiology of behavior.
The Yu Lab investigates the complex connections between neurons that link sensation to behavior. In particular, the lab studies the mouse olfactory system, which detects odors, and the related vomeronasal system, which detects pheromones. Uncovering the neuronal mechanisms can advance scientific understanding of the development of the nervous system and neurological diseases. In their early studies, the Yu Lab established the first mouse line expressing a genetically encoded calcium sensor (GECI) to detect calcium signals in the nervous system. This development allowed researchers to record signals for hundreds of cells simultaneously. Using this technique, Yu reported how vastly different sets of neurons respond to male or female pheromones. They also identified two classes of pheromone receptors crucial for the mating process in mice. By developing additional genetic tools and manipulations of neuronal activity, the lab later discovered a brief “critical period” in the mouse olfactory system to fix neuronal wiring problems — a window that lasts until about a week after mice are born. This early plasticity allows the animals to adapt to their odor environment, allowing them to change their responses to innately aversive odors when raised in an environment with these odors.
Research Projects
Our research team is dedicated to understanding how developmental and aging processes impact the sense of smell. We focus on the molecular mechanisms that control the generation and development of olfactory sensory neurons. These neurons are unique in mammals because they have the ability to regenerate and extend long axons to the brain. By uncovering what makes these neurons capable of regeneration, we aim to provide insights into neuronal regeneration as a whole. This research is particularly important because the inability to smell is often one of the earliest signs of neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and Huntington’s. Understanding how aging affects the regenerative capacity of sensory neurons could lead to the development of interventions that slow down or prevent this decline. We are actively applying the knowledge gained from our studies to animal models of nerve injury and neurodegenerative diseases to evaluate the effectiveness of various therapeutic interventions.
In parallel, our team conducts comprehensive studies on how the brain processes neuronal information to create perceptions and drive behavior. This research examines the brain circuits involved in processing information to generate specific responses and behaviors. One area of focus is understanding how innate odor perceptions, such as reflexive responses to aversive odors, are generated and processed by the brain. We employ a wide range of methodologies, including spatial -omics, whole-brain activity mapping, circuit tracing, brain imaging in behaving animals, and electrophysiology, to explore the neural circuitry and the transformation of information within these circuits. Beyond studying innate odor and pheromone perception, we are also exploring the neural mechanisms underlying social behaviors. Through carefully designed behavioral paradigms, we aim to map the neural circuits associated with social dominance and frustration, providing a deeper understanding of the neural basis of social interactions.