The Jang lab aims to understand how dietary nutrient metabolism causes diseases.
We also seek to identify disease-associated metabolites that impact organ metabolism, signal transduction, and genetic/epigenetic landscapes.
To this end, we use metabolomics, lipidomics, and stable isotope tracing in genetic animal models and human patients.
We focus on metabolic disease, e.g., obesity, diabetes, alcoholic and non-alcoholic fatty liver, cardiovascular disease, and cancers.
- 5/1/2020. The Jang lab is born healthy, despite the pandemic.
- 6/12/2020. Hosung‘s Angiopoietin-2 paper is out in Nature Communication (https://www.nature.com/articles/s41467-020-16795-4).
- 6/22/2020. Cholsoon and Shogo’s Khk paper is out in Nature Metabolism (https://www.nature.com/articles/s42255-020-0222-9).
- 7/27/2020. Lavina joined the lab. She made the lab much more vibrant.
- 7/28/2020. Cholsoon received an AASLD Pinnacle Research Award. (http://www.aasldfoundation.org/2020-research-and-career-development-award-recipients)
- 8/7/2020. Q Exactive LC-MS started collecting the lab’s first data.
- 8/24/2020. Johnny, an MD/PhD student, started a rotation. On day 3, he got a beautiful peak. Goosebumps!
- 9/1/2020. Sunhee joined the lab. Now, we have a real chemist.
- 10/1/2020. Johnny joined the lab. Officially, the first student of the lab.
- 10/1/2020. Hosung joined the lab. Now, we have a real bioinformatics expert.
- 10/1/2020. Temoc, a PhD student, started a rotation.
- 10/1/2020. Cholsoon received Edward Mallinckrodt, Jr. Foundation Award. (https://www.som.uci.edu/news_releases/cholsoon-jang.asp).
- 10/15/2020. Danielle and Cholsoon‘s human heart AV metabolomics paper is out in Science. (https://science.sciencemag.org/content/370/6514/364).
Cholsoon Jang, PhD (Principal investigator)
- Assistant Professor of Biological Chemistry (2020.5-)
- Postdoc at Princeton University (Rabinowitz lab, ADA postdoctoral fellow, 2016.6-2020.4)
- PhD at Harvard Medical School (Arany lab, AHA predoctoral fellow, Lotte scholarship, 2009.9-2015.11)
- Military Service in GenExel-Sein, a biotech company (2006.3-2009.2)
- BS and MS in Biological Sciences at Korea Advanced Institute of Science and Technology (2000.3-2006.2)
- Awards: AASLD Pinnacle Research Award in Liver Disease, Edward Mallinckrodt, Jr. Foundation Grant
Sunhee Jung, PhD (Postdoctoral Fellow)
Sunhee obtained her PhD in Chemistry at Sungkyunkwan University. She has expertise in analytical chemistry and nutrient metabolism. She likes sunset and music and believes that sincerity is essential for every step in life.
Hosung Bae, PhD (Postdoctoral Fellow)
Johnny Le (MD/PhD student)
Johnny is a MD/PhD student, studying skin metabolism. He has expertise in immunology with a focus on autoimmunity. In his free time, he enjoys traveling and spending time with his family outdoors.
Lavina Mathur, MS (Lab Technician)
Lavina obtained her MS in Biotechnology Management at UC Irvine. Her research interests are the link beween metabolism and signaling pathways in cancers.
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 sole 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 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 enhanced or ablated intestinal fructose clearance, we also demonstrate that this intestinal fructose clearance prevents fructose-induced liver pathology.
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, generating fundamental datasets containing over 700 significant cases of organ-specific metabolite production or consumption. By applying this technology combined with in vivo isotope tracing, we seek to understand how various physiological or pathological conditions shift inter-organ metabolic crosstalk.
Jang C et al. Cell Metab. (2019), Murashige D*, Jang C* et al. Science (2020)
3. Metabolomics and isotope tracing technology development
Our technological platform is the state-of-the-art metabolomics, non-radioactive stable isotope tracing and quantitative analysis. 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 unknown bioactive metabolites and quantitatively assess metabolic pathway activities (fluxes) at the whole-body level.
Jang C et al. Cell (2018).
- 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*,#, Wada S*, Yang S, Gosis B, Zeng X, et al. (2020). The small intestine shields the liver from fructose-induced steatosis. Nature Metabolism 2:586-593. #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. Nature Communications 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 Metabolism 31:809-821.
- Guan D, Xiong Y, Trinh TM, Xiao Y, Hu W, Jiang C, Dierichx P, Jang C, Rabinowitz JD, Lazar M. (2020). The hepatocyte clock and feeding control chronophysiology of multiple liver cell types. Science 369:1388-1394.
- Hui S*,#, Cowan AJ*, Zeng X, Yang L, TeSlaa T, Li X, Bartman C, Zhang Z, Jang C, Wang L, Lu W, Rojas J, Baur J, Rabinowitz JD#. (2020). Quantitative fluxomics of circulating metabolites. Cell Metabolism 32:676-688.
- Murashige D*, Jang C*, Neinast M, Edwards JJ, Cowan A, Hyman MC, Rabinowitz JD, Frankel DS, Arany Z. (2020). Comprehensive quantification of fuel use by the failing and nonfailing human heart. Science 370:364-368.
- Jang C, Hui S, Zeng X, Cowan AJ, Wang L, et al. (2019). Metabolite exchange between mammalian organs quantified in pigs. Cell Metabolism 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 Metabolism 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 Metabolism 27:351-361.
- 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. Nature Medicine 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. Circulation 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
Postdoc and student positions are available.
We are looking for lab members who are highly motivated to study organismal metabolism. Email your CV to firstname.lastname@example.org