Congcong He

Congcong He, PhD
Assistant Professor
Cell and Molecular Biology


Autophagy in metabolic regulation and pathogenesis of metabolic diseases

Research Cluster: Cell and Molecular Biology

E-mail:   
congcong.he@northwestern.edu

To visit the Congcong He lab website, CLICK HERE

The research in my lab is centered on autophagy, a lysosomal degradation pathway essential for nutrient recycling, cellular maintenance and physiological function. Autophagy is induced by various stress conditions, and allows cells to adapt to changing nutrient and energy demands through protein catabolism. Malfunction of autophagy is implicated in a variety of diseases such as cancer, neurodegeneration, infection and aging. There are many unexplored questions in this growing field, spanning from the molecular mechanisms of autophagy induction to the physiological roles of autophagy in health and diseases. Our research interest focuses on the roles and mechanisms of autophagy in the metabolic regulation of mammals and in the pathogenesis of metabolic diseases in human, such as obesity and type 2 diabetes. There are currently two directions of study in our lab:

1. The function of autophagy in exercise-induced metabolic benefits using mouse models with deficient or hyperactive autophagy. Physical exercise has beneficial effects on human health, including protection against metabolic disorders such as diabetes. However, the cellular mechanisms underlying these effects are not fully understood. We recently discovered that acute exercise potently induces autophagy in multiple organs of fed mice, including β cells, adipose tissue, liver, muscle and brain. To study the role of exercise-induced autophagy, we generated knock-in mouse models with different autophagy activities as in vivo tools. We discovered that mutant mice deficient in exercise-induced autophagy exhibit decreased endurance and altered glucose metabolism during acute exercise. More importantly, these mutant mice are more susceptible to high-fat diet (HFD)-induced obesity, and are not protected from HFD-induced insulin resistance by chronic exercise as wild-type mice. These findings suggest that exercise-induced autophagy may play an important role in mediating some of the beneficial metabolic effects of exercise. We are also expanding our studies on additional open questions regarding autophagy and exercise, for example, whether the signals that trigger exercise-induced autophagy in the brain are cell-autonomous or derived from extrinsic systemic cues, and whether exercise-induced autophagy mediates the beneficial effects of exercise on diseases besides diabetes, such as neurodegeneration and aging.

2. Characterizing the mechanism of Beclin 2, a novel Beclin family member, in autophagy, endolysosomal trafficking of G protein-coupled receptors (GPCRs), and metabolism. The molecular mechanism of mammalian autophagy and its relationship to other lysosomal degradation pathways remain incompletely understood. We recently cloned and characterized a novel autophagy gene in the beclin family, and named it beclin 2. We discovered that Beclin 2 plays an important role in autophagy and lysosomal degradation of a specific subset of GPCRs. beclin 2 homozygous knockout (KO) mice have decreased embryonic viability, and heterozygous KO mice have defective autophagy, increased levels of GPCRs in the brain, elevated food intake, and obesity and insulin resistance. We also generated beclin 2 conditional KO mice to study its tissue-specific functions. Our initial findings suggest that Beclin 2 is a novel converging regulator of autophagy and GPCR turnover, and highlight the functional and mechanistic diversity of Beclin family members in autophagy, endolysosomal trafficking and metabolism. Our long-term goal is to elucidate the mechanisms of Beclin 2 in regulating autophagy, GPCR signaling, obesity and related diseases, and their crosstalk. Since GPCRs have versatile biological functions, our study, in the long run, will also result in novel insights on a wider spectrum of human disorders.

Selected Publications:

He C, Bassik MC, Moresi V, Sun K, Wei Y, Zou Z, An Z, Loh J, Fisher J, Sun Q, Korsmeyer S, Packer M, May HI, Hill JA, Virgin HW, Gilpin C, Xiao G, Bassel-Duby R, Scherer PE and Levine B. Exercise-induced BCL2-regulated autophagy is required for muscle glucose homeostasis. Nature. 481, 511-5. 2012. PMCID: 3518436

He C, Sumpter R, Jr. and Levine B. Exercise induces autophagy in peripheral tissues and in the brain. Autophagy. 8 (10). 1548-51. 2012. PMCID: 3463459

He C, Wei Y, Sun K, Li B, Dong X, Zou Z, Liu Y, Kinch LN, Khan S, Sinha S, Xavier RJ, Grishin NV, Xiao G, Eskelinen E-L, Scherer PE, Whistler JL and Levine B. Beclin 2 functions in autophagy, degradation of G protein-coupled receptors, and metabolism. Cell. 154 (5). 1085-99. 2013. PMID: 23954414



Pub med

View Publications by Congcong He listed in the National Library of Medicine (PubMed).