Research Areas

Physiological Nutrition and Tumor Metabolism

Our laboratory employs metabolomics, metabolic flux analysis, and related technologies to investigate the liver-centered inter-organ metabolic interaction network. We aim to identify unknown metabolites and intervention targets that regulate the onset and progression of metabolic diseases such as obesity, cancer, and cachexia.

Research Description

Metabolism in the human body is a highly dynamic and tightly regulated network, with reaction rates constantly shifting in response to physiological states, nutritional intake, and disease progression. While conventional metabolomics provides a snapshot of metabolite abundance, metabolic flux analysis captures the dynamics of metabolic pathways. Together, these approaches offer a more comprehensive view of disease mechanisms and the impact of nutritional regulation.

Modern lifestyles, characterized by overnutrition and poor dietary habits, are major contributors to obesity, non-alcoholic fatty liver disease, diabetes, and various cancers. After intestinal absorption, nutrients first reach the liver—the body’s central metabolic hub. The liver not only integrates and transforms exogenous nutrients but also communicates closely with peripheral organs such as muscle and adipose tissue through secreted metabolites and substrate availability. Understanding this liver-centered inter-organ metabolic dialogue is therefore essential for deciphering the pathogenesis of metabolic diseases.

Based on these considerations, our laboratory integrates metabolomics, metabolic flux analysis, and single-cell genomics, using in vitro cell models, rodent disease models, and clinical samples as experimental systems. Our research focuses on three main areas:

1. Mining the “dark metabolome”: Using stable isotope tracing and multi-omics integration, we screen for disease-relevant unknown metabolites from large sets of unannotated mass spectral features, followed by structural elucidation and functional validation.

2. Liver–peripheral organ metabolic crosstalk: We map the flow of metabolites between the liver and peripheral organs (e.g., muscle, adipose tissue, intestine) to identify key nodes in inter-organ regulatory networks under disease conditions.

3. Precision modulation through nutritional interventions: We investigate how dietary interventions such as amino acid restriction and ketogenic diets reshape metabolic networks and explore their synergistic effects with chemotherapy and immunotherapy.

Brief Biography
2021–Now: PI, Shanghai Institute of nutrition and health, Chinese Academy of Sciences
2017-2021: Postdoctoral Fellow, Lewis Sigler Institute, Princeton University, USA
2016-2016: Postdoctoral in chemistry and Bioengineering, Rice University, USA
2010-2016: Doctor of chemistry and Bioengineering, Rice University, USA
2006-2010: Bachelor, School of chemical engineering, Tianjin University

Selected Publications (*Corresponding Author)

1. 1. Cao Y, Li S, Liu Z, Jia Z, Zhuang W, Pan X, Zhou J, Yang L*, Wang L*. SMART: an approach for accurate formula assignment in spatially resolved metabolomics. Analytical Chem. 2025; 97(29): 15570-15578.
2. 2. Xin C#, Cai M#, Jia Q#, Huang R, Li, R., Wang J, Li Z, Zhao Q, Liu T, Zhuang W, Zhou J, Li S, Tao Y*, Wang L*, & Yang L*. Dietary sulfur amino acid restriction improves metabolic health by reducing fat mass. Life Metab. 2025;4(3):loaf 009.
3. 3. Zhang L#, Xin C#, Wang S, Zhuo S, Zhu J, Li Z, Liu Y, Yang L*, Chen Y*. Lactate transported by MCT1 plays an active role in promoting mitochondrial biogenesis and enhancing TCA flux in skeletal muscle. Sci Adv. 2024; 10:eadn4508.
4. 4. Yang L, TeSlaa T, Ng S, Nofal M, Wang L, Lan T, Zeng X, Cowan A, McBride M, Lu W, Davidson S, Liang G, Oh TG, Downes M, Evans R, Von Hoff D, Guo JY, Han H, Rabinowitz JD*. Ketogenic diet and chemotherapy combine to disrupt pancreatic cancer metabolism and growth. Med. 2022; 3:119-136.
5. 5. Yang L, Garcia Canaveras JC, Chen Z, Wang L, Liang L, Jang C, Mayr JA, Zhang Z, Ghergurovich JM, Zhan L, Joshi S, Hu Z, McReynolds MR, Su X, White E, Morscher RJ, Rabinowitz JD. Serine Catabolism Feeds NADH when Respiration Is Impaired. Cell Metab. 2020; 31(4):809-821.e6.
6. 6. Han C^#, Yang L^#, Choi HH#, Baddour J, Achreja A, Liu Y, Li Y, Li J, Wan G, Huang C, Ji G, Zhang X, Nagrath D*, Lu X*. Amplification of USP13 drives ovarian cancer metabolism. Nat Commun. 2016; 7:13525.
7. 7. Yang L, Achreja A, Yeung TL, Mangala LS, Jiang D, Han C, Baddour J, Marini JC, Ni J, Nakahara R, Wahlig S, Chiba L, Kim SH, Morse J, Pradeep S, Nagaraja AS, Haemmerle M, Kyunghee N, Derichsweiler M, Plackemeier T, Mercado-Uribe I, Lopez-Berestein G, Moss T, Ram PT, Liu J, Lu X, Mok SC, Sood AK*, Nagrath D*. Targeting Stromal Glutamine Synthetase in Tumors Disrupts Tumor Microenvironment-Regulated Cancer Cell Growth. Cell Metab. 2016; 24:685-700.