The Jang lab aims to understand how dietary nutrients and their metabolic products induce diseases.
Using LC-MS-based metabolomics, lipidomics, and in vivo isotope tracing in disease animal models and human patients, we elucidate how nutrients are metabolized by the host organs and microbiota.
We also study how disease-associated nutrient metabolites alter energy metabolism, signaling pathways, and genetic/epigenetic landscapes, triggering disease.
We focus on metabolic disease, including obesity, diabetes, NAFLD, NASH, liver and colon cancer.
Cholsoon Jang, PhD (Principal investigator)
- Assistant Professor at UC Irvine (2020.5-)
- Postdoc at Princeton University (Rabinowitz lab, ADA postdoctoral fellow, 2016.6-2020.4)
- PhD at Harvard Medical School (Arany lab, AHA pre-doctoral fellow, Lotte scholarship awardee, 2009.9-2015.11)
- Military Service in a biotech company (2006.3-2009.2)
- BS and MS in Biological Sciences at Korea Advanced Institute of Science and Technology (KAIST) (2000.3-2006.2)
- Current Affiliations: Department of Biological Chemistry,
Chao Family Comprehensive Cancer Center, UC Irvine School of Medicine.
Center for Epigenetics and Metabolism
Southern California Research Center for Alcoholic Liver and Pancreatic Diseases (ALPD) and Cirrhosis
Awardee, Pinnacle Research in Liver Disease, American Association for the Study of Liver Disease (AASLD)
Sunhee Jung, PhD (Postdoctoral Fellow)
Sunhee obtained her PhD in Chemistry at Sungkyunkwan University. Her expertise are analytical chemistry and nutrient metabolism.
Hosung Bae, PhD (Postdoctoral Fellow)
Lavina Mathur, MS (Lab Assistant)
Lavina obtained her MS in Biotechnology Management at UC Irvine. Her research interests are cancer metabolism and signaling pathway.
Postdoc and student positions are available.
We are looking for lab members who are highly motivated to study metabolism. Please email your CV to firstname.lastname@example.org
1. Nutrient metabolism
There are numerous associations between foods and diseases (e.g., the link between soda drinking and fatty liver). In most cases, however, the causality is elusive or underlying mechanisms are controversial. This problem likely originates from our incomplete understanding of how nutrients are metabolized in our body.
One example is the metabolism of dietary fructose, a risk factor for obesity, diabetes, and fatty liver. It is commonly believed that the liver is the main site of fructose metabolism. However, using in vivo isotope tracing in mice, we recently showed that the small intestine clears most physiological doses of fructose by converting fructose to glucose and other metabolites before fructose reaches the liver. Only high fructose doses overwhelm the small intestine’s capacity, resulting in fructose spillover to the liver and colonic microbiota and causing excessive fatty acid synthesis in the liver. By generating genetic mouse models that have increased or decreased intestinal fructose clearance, we are seeking to understand this process and find ways to prevent fructose-induced pathologies.
Jang C et al. Cell Metab. (2018),
Zhao S*, Jang C* et al. Nature (2020),
Jang C*, Wada S* et al. Nat. Metab. (2020).
2. Inter-organ metabolic communication
In our body, no single organ is isolated. Through lifelong cardiac contraction that circulates blood, organs continually exchange metabolites for homeostasis. One famous example is the Cori cycle, in which lactate made by skeletal muscle is converted into glucose by the liver and glucose feeds skeletal muscle.
Each organ is fed by arterial blood and drained by venous blood. By measuring arterio-venous (AV) metabolite concentration differences, we can quantify organ-specific metabolite release and uptake.
Using this method, we systematically analyzed metabolite exchange in fasted pigs and revealed sources and sinks of the ~300 circulating metabolome, resulting in a fundamental dataset containing over 700 significant cases of organ-specific metabolite production or consumption. By applying this technology combined with in vivo isotope tracing, we are investigating how various physiological (feeding, high insulin) or pathological conditions (diabetes and cancers) alter inter-organ metabolic crosstalk.
Jang C et al. Cell Metab. (2019)
3. Metabolomics and isotope tracing technological development
Our technological platform is the state-of-the-art metabolomics, non-radioactive stable isotope tracing and quantitative modeling. We have an in-house high-sensitivity, high-resolution Q-Exactive Orbitrap LC-MS and routine access to NMR, Q-TOF, Triple-Quad and MALDI-TOF MS in the Chemistry Department core facility. By developing and optimizing these tools, we aim to identify bioactive metabolites and quantitatively assess metabolic pathway activities (fluxes) in specific organs and between organs.
Jang C et al. Cell (2018).
- Jang C*,#, Wada S*, Yang S, Gosis B, Zeng X, et al. (2020). The small intestine shields the liver from fructose-induced steatosis. Nat. Metab. (In press). #corresponding author
- Bae H, Hong KY, Lee CK, Jang C, Lee SJ, et al. (2020). Angiopoietin-2-integrin α5β1 signaling enhances vascular fatty acid transport and prevents ectopic lipid-induced insulin resistance. Nat. Commun. 12;11(1):2980.
- Yang L, Garcia Canaveras JC, Chen Z, Wang L, Liang L, Jang C, et al. (2020). Serine catabolism feeds NADH when respiration is impaired. Cell Metab. 31:809-821.
- Zhao S*, Jang C*, Liu L, Uehara K, Gilbert M, et al. (2020). Dietary fructose feeds hepatic lipogenesis via microbiota-derived acetate. Nature. 579:586-591.
- Jang C, Hui S, Zeng X, Cowan AJ, Wang L, et al. (2019). Metabolite exchange between mammalian organs quantified in pigs. Cell Metab. 30:596-606.
- Lee CK, Jeong SH, Jang C, Bae H, Kim YH, et al. (2019) Tumor metastasis to lymph nodes requires YAP-dependent metabolic adaptation. Science 363:644-649.
- Neinast M*, Jang C*, Hui S, Murashige DS, Chu Q, et al. (2019). Quantitative analysis of the whole-body metabolic fate of branched-chain amino acids. Cell Metab. 29:417-429.
- Kim B, Jang C, Dharaneeswaran H, Li J, Bhide M, et al. (2018) Endothelial pyruvate kinase M2 maintains vascular integrity. J. Clin. Invest. 128:4543-4556.
- Jang C, Li C, Rabinowitz JD. (2018) Metabolomics and isotope tracing. Cell 173:822-837. (Review)
- Jang C, Hui S, Lu W, Cowan AJ, Morscher RJ, et al. (2018) The small intestine converts dietary fructose into glucose and organic acids. Cell Metab. 27:351-361. (Highlighted in Cell Metab, Science, Rev. Endocrinol, Sci. Transl. Med, and Economics).
- Mirtschink P, Jang C, Arany Z, Krek W. (2018) Fructose metabolism, cardiometabolic risk, and the epidemic of coronary artery disease. Eur. Heart J. 39:2497-2505. (Review)
- Guan D, Xiong Y, Borck PC, Jang C, Doulias PT, et al. (2018) Diet-Induced Circadian Enhancer Remodeling Synchronizes Opposing Hepatic Lipid Metabolic Processes. Cell 174:831-842.
- Lanaspa MA, Andres-Hernando A, Orlicky DJ, Cicerchi C, Jang C, et al. (2018) Ketohexokinase C blockade ameliorates fructose-induced metabolic dysfunction in fructose-sensitive mice. J. Clin. Invest. 128:2226-2238.
- Hui S, Ghergurovich JM, Morscher RJ, Jang C, Teng X, et al. (2017) Glucose feeds the TCA cycle via circulating lactate. Nature 551:115-118.
- Lee G, Zheng Y*, Cho S*, Jang C, England C, et al. (2017) Post-transcriptional regulation of de novo lipogenesis by mTORC1-S6K1-SRPK2 signaling. Cell 171:1545-1558.
- Kim B*, Li J*, Jang C, Arany Z. (2017) Glutamine fuels proliferation but not migration of endothelial cells. EMBO J. 36:2321-2333.
- Jang C*, Oh SF*, Wada S, Rowe GC, Liu L, et al. (2016) A branched chain amino acid metabolite drives vascular fatty acid transport and insulin resistance. Nat. Med. 22:421-426.
- Wada S, Neinast M*, Jang C*, Ibrahim YH, Lee G, et al. (2016) The tumor suppressor FLCN mediates an alternate mTOR pathway to regulate browning of adipose tissue. Genes Dev. 30:2551-2564.
- Rowe GC*, Raghuram S*, Jang C, Nagy JA, Patten IS, Goyal A, Chan MC, Liu LX, Jiang A, Spokes KC, Beeler D, Dvorak H, Aird WC, Arany Z. (2014) PGC-1α induces SPP1 to activate macrophages and orchestrate functional angiogenesis in skeletal muscle. Circ. Res. 115:504-517.
- Jang C and Arany Z. (2013) Metabolism: Sweet enticements to move. Nature 500:409-411. (News & views).
- Patten IS*, Rana S*, Shahul S, Rowe GC, Jang C, et al. (2012) Cardiac angiogenic imbalance leads to peri-partum cardiomyopathy. Nature 485:333-338.
- Kataru RP*, Kim H*, Jang C, Choi DK, Koh BI, et al. (2011) T lymphocytes negatively regulate lymph node lymphatic vessel formation. Immunity. 34:96-107.
- Jang C, Koh YJ, Lim NK, Kang HJ, Kim DH, et al. (2009) Angiopoietin-2 exocytosis is stimulated by sphingosine-1-phosphate in human blood and lymphatic endothelial cells. Arterioscler. Thromb. Vasc. Biol. 29:401-407.
- Jang C, Lee G, Chung J. (2008) LKB1 induces apical trafficking of Silnoon, a monocarboxylate transporter, in Drosophila J. Cell Biol. 183:11-17.
- Jeon BH, Jang C, Han J, Kataru RP, Piao L, et al. (2008) Profound but dysfunctional lymphangiogenesis via vascular endothelial growth factor ligands from CD11b+ macrophages in advanced ovarian cancer. Cancer Res. 68:1100-1109.
For complete list of publications,
- Pubmed: https://www.ncbi.nlm.nih.gov/pubmed/?term=cholsoon+jang
- Google Scholar: https://scholar.google.com/citations?user=Wsdt99kAAAAJ&hl=en&oi=ao