Uncovering how autophagy links metabolism to behavior in health and disease.
Welcome to the He Lab
In the He Lab, we study how intracellular quality control shapes metabolism and behavior, and how to therapeutically optimize its function to prevent and treat diseases.
Our research focuses on autophagy, an intracellular quality control mechanism that enables nutrient recycling, cellular maintenance and physiological function. Triggered by stressors like fasting and exercise, autophagy helps cells adapt to changing nutrient and energy demands through protein catabolism.
We explore:
- How autophagy regulates metabolism.
- How autophagy dysfunction contributes to metabolic and neurological disorders, including obesity, type 2 diabetes, neurodegeneration and substance use disorders.
Our work has shown that upregulating autophagy can:
- Mediate exercise-induced metabolic benefits.
- Protect against neurodegeneration in Alzheimer’s disease models.
We are interested in demonstrating how the autophagy machinery recognizes different types of cargos and regulates their transport, degradation and secretion — including aggregate-prone proteins, secretory proteins and membrane receptors — in metabolic organs and various neuronal cell types in the brain. We also study how such degradation influences metabolic and behavioral alterations.
Lab Leadership
Congcong He, PhD
Associate Professor of Cell and Developmental Biology
Featured Research
Exercise-Induced Autophagy in Skeletal Muscle Visualized by GFP-LC3
Image Left: Diffused GFP-LC3 signal in wild-type skeletal muscle before exercise
Image Right: GFP-LC3 puncta (autophagosomes) in wild-type skeletal muscle after 80 min of exercise
Wild-Type vs. Autophagy-Deficient (BCL2 AAA) Mouse
Top: At the start of running (10 m/min)
Bottom: After 95 min of running (18 m/min)
Upper lanes: wild-type mouse; Lower lanes: autophagy-deficient (BCL2 AAA) mouse
Becn2 harnessing autophagy and receptors (2014)
Becn2/Beclin 2 is a newly identified Beclin family member that is essential for autophagy. It also regulates lysosomal degradation of endocytosed G protein-coupled receptors (GPCRs), through the N-terminal interaction of Beclin 2 with an adaptor protein GASP1. The cover image illustrates the dual roles of the "cowboy" Beclin 2 (containing an N-terminal domain, CCD (coiled-coil domain) and ECD (evolutionarily conserved domain)): riding the autophagy "horse," and harnessing the 7-transmembrane GPCR "cow" by the N-terminal "arm" and the GASP1 "lasso." The background mountain depicts plasma membrane, and cacti and rocks represent various intracellular organelles (including mitochondria, ER and Golgi) and cytosolic proteins.
The image was designed by Congcong He, and artwork illustrated by Dorothy Zhu.
Differential roles of autophagy in insulin production versus sensitivity (2018)
Autophagy, an essential lysosomal degradation pathway, plays different roles in distinct metabolic tissues. Hyperactive autophagy benefits insulin-responsive tissues on insulin sensitivity, but reduces pancreatic β cell function by excessive autophagic degradation of insulin-containing vesicles (named vesicophagy). The wave represents an autophagic membrane engulfing insulin granules. The two peaks in the background represent two non-overlapping rheostat curves for autophagy function in insulin-responsive tissues (right) versus in insulin-producing β cells (left), a shift driven by vesicophagy.
The image was designed by Kenta Kuramoto and Congcong He, and modified from Ukiyo-e artworks.
Autophagic Regulation of Drug Reward Behaviors
In this short video, Congcong He, PhD, discusses how the addictive effects of cocaine are regulated by an autophagy protein Becn2 and can be prevented by autophagy inhibitors. (2021)
