10th Annual Canadian Neurometabolic Meeting

Zachary Knight is a Professor in the Department of Physiology at UCSF and an Investigator of the Howard Hughes Medical Institute. His lab studies the neural mechanisms that control homeostasis, including especially the regulation of hunger, thirst and body temperature.

Zachary received his B.A. in Chemistry from Princeton University and his Ph.D. in Chemistry from UCSF. During his Ph.D. research in the lab of Kevan Shokat, Zachary discovered some of the first selective inhibitors of PI3-kinase and mTOR. In 2007, Zachary co-founded Intellikine to develop these compounds into drugs, which led to the development and approval of duvelisib for the treatment of cancer. Zachary then switched fields from chemistry to physiology and performed postdoctoral research in the lab of Jeffrey Friedman at Rockefeller University, where he developed genetic methods for identifying neural cell types in the mouse brain.

Zachary returned to UCSF in 2012 to start his independent research group investigating the neurobiology of homeostasis. His lab is recognized for performing the first neural recordings of many of the key cell types in the brain that control homeostasis, including neurons for hunger (AgRP neurons), satiety (POMC, GCG, and PRLH neurons), thirst (SFO neurons) and body temperature (PACAP neurons). These experiments led to the general discovery that homeostatic neurons in the hypothalamus and brainstem - long thought to function primarily by reacting to physiologic imbalances - instead utilize sensory cues from the outside world to anticipate physiologic changes and adjust behavior preemptively. This has transformed our understanding of how the brain controls hunger and thirst.

Zachary's work has been recognized by awards from the Sloan, McKnight, Rita Allen, Klingenstein, and Brain and Behavior Research Foundations; the Robertson Investigator Award from the New York Stem Cell Foundation; the New Innovator, Pathway to Independence, and PECASE Awards from the National Institutes of Health; the Pathway Award from the American Diabetes Association; and the Helmholtz Young Investigator in Diabetes Award. In 2018, he was named an Investigator of the Howard Hughes Medical Institute.

Dr. Melissa Chee earned her PhD in Neuroscience from the University of Alberta and completed postdoctoral training at Harvard Medical School.

The Chee lab investigates the neurobiology of obesity. Dr. Chee’s latest research shows that fructose produces apostrophe in the brain that convey hunger and over-eating. A ubiquitous sugar, it permeates the Canadian diet disguised as sweeteners like glucose-fructose syrup or high fructose corn syrup. While sugar is necessary to fuel our mind and body, Dr. Chee’s work cautions against excessive intake of fructose and advocates for restrictions on sugary drinks and processed food where fructose is especially pervasive. Her research team implements cutting-edge neuroscience to monitor and regulate the activity of individual brain cells important for body weight control.

Dr. Lam earned his PhD in Physiology at the University of Toronto and completed is post-doctoral training at the Albert Einstein College of Medicine in New York City. His main focus has been to elucidate nutrient and hormone sensing mechanisms in the gut and the brain that regulate hepatic glucose production, hepatic VLDL-TG secretion and food intake to maintain glucose, lipid and energy homeostasis.

The Lam lab aims to unveil novel therapeutic molecular targets in the gut and the brain that lower blood glucose and lipid levels as well as body weight in diabetes and obesity. His lab discovered that there are nutrient sensing-dependent molecules in the gut that are sufficient and necessary for gut microbiota, metformin and bariatric surgery to lower blood glucose levels in diabetic and obese rodents (Bauer et al. Cell Metab 2017; Duca et al. Nat Med 2015; Cote et al. Nat Med 2015; Rasmussen et al. Cell Metab 2014; Breen et al. Nat Med 2012; Cheung et al. Cell Metab 2009; Wang et al. Nature 2008). In parallel, the Lam lab examines nutrient sensing-dependent molecules in the brain that lower blood glucose and lipid levels as well as body weight in diabetic and obese rodents (Yue et al. Nat Commun 2016; Yue et al. Nat Commun 2015; Yue et al. Circ Res 2012).