Zachary Knight, PhD


Assistant Professor, UCSF School of Medicine

Ph.D. in Chemistry and Chemical Biology, University of California - San Francisco
B.A. in Chemistry, Princeton University

The Knight lab studies neural circuits in mice that control feeding and other motivated behaviors central to survival. The goal of the lab's research is to understand how the circuits are able to sense the needs of the body, and thus generate specific behavioral responses that restore homeostasis. A major challenge in this field is that the homeostatic circuits are embedded within brain structures such as the hypothalamus, that contain a vast diversity of neural cell types. As a result, little is known about the specific cell types, interconnections, and activity dynamics that drive these fundamental behaviors. To address that challenge, the lab develops genetic tools that enable the use of RNA sequencing to identify molecular markers for functional populations of neurons in those brain regions (Knight et al, Cell, 2012; Ekstrand et al., Cell, 2014). Those molecular markers are used as entry points to visualize and manipulate the underyling cells - using a range of modern approaches in neuroscience including optogenetics, calcium imaging, slice and in vivo electrophysiology, and viral tracing. 

Projects: 

The long-term goal of the Knight lab is to elucidate the structure and dynamics of the neural circuits that control homeostasis to gain an understanding of how they give rise to goal-directed behaviors and further how they become dysregulated in conditions such as obesity. Recently, the lab reported the first in vivo recordings of the activity of AgRP and POMC neurons, the two most widely studied cell types in the mouse brain that control hunger (Chen et al., Cell, 2015). Those experiments unexpectedly revealed that AgRP and POMC neurons are potently regulated by the sensory detection of food – that is, the mere sight and smell of food is sufficient to rapidly “reset” the activation state of these neurons induced by food deprivation. The discovery suggests that AgRP and POMC neuron activity directly controls appetitive behaviors, such as foraging, and promote the discovery of food. An ongoing interest of the lab is to understand how these and other homeostatic circuits integrate sensory information from the outside world with internal signals arising from the body in order to generate and shape goal-directed behaviors such as feeding.

Zachary Knight earned his B.A. in Chemistry from Princeton University and his Ph.D. in Chemical Biology from UCSF. Following postdoctoral training at Rockefeller University, Dr. Knight joined the Department of Physiology as an Assistant Professor.

 

Dr. Knight is a Robertson Neuroscience Investigator of the New York Stem Cell Foundation. His work has been recognized by awards from the Sloan, McKnight, Rita Allen, Klingenstein, and Brain and Behavior Research Foundations, as well as NIH New Innovator and Pathway to Independence Awards. Most recently, Dr. Knight received a Pathway Award from the American Diabetes Association.

Elizabeth Cooke, Specialist

Yen-Chu Lin, Specialist

Erica Huey, Specialist

Ailar Poormoghaddam, Specialist

Gwendowlyn Daly, Specialist

Jacob Carlson, Postdoctoral Fellow

Chan Lek Tan, Postdoctoral Fellow

Chris Zimmerman, Neuroscience Graduate Student

Yiming Chen, Neuroscience Graduate Student

Tzu-Wei Kuo, Neuroscience Graduate Student

David Leib, Neuroscience Graduate Student

Alissa Boado, Adminstrative Assistant