Lei Jiang, Ph.D.
Assistant Professor, Molecular & Cellular Endocrinology
Research Area
Molecular and Cellular Endocrinology
Metabolic Alteration in Obesity and Diabetes
Central Carbon Metabolism in Cancer
Systemic Metabolic Flux Analysis
Lei Jiang received his bachelor's degree from Wuhan University, and then completed his Ph.D. at Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, where he received the Dean Award and Unilever Scholarship, and he was also honored as a Merit student.
After his postdoctoral training in University of Texas Southwestern Medical Center at Dallas, he joined City of Hope as an assistant professor in the department of Molecular & Cellular Endocrinology. During his research training, Dr. Jiang has had several high-profile publications in Nature, Nature Cell Biology, Cell, Molecular Cell, Hepatology, PNAS and Metabolic Engineering. His research interest is to elucidate the molecular mechanisms regulating nutrient homeostasis during the development and progress of metabolic diseases such as diabetes and cancer.
His research particularly focuses on the compartmentalized central carbon metabolism (glycolysis and oxidative phosphorylation) under pathological conditions, through the application of the leading- edge mass spec based metabolic tracing and systemic bioengineering.
Duarte Cancer Center
1500 East Duarte Road
Duarte, CA 91010
Duarte, CA 91010
2009, Ph.D., Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
2004, B.S. , Wuhan University, Wuhan, China
2009-2016, UT Southwestern Medical Center, Dallas, TX
Visit the Lei Jiang Lab page to learn more about his research.
Metabolism is a fundamental biological phenomenon. Dysregulated metabolism contributes to a variety of disease, including cancer and diabetes, which are known as metabolic disease. Metabolic alteration has been studied at several levels, from the whole organism to the single cells and subcellular organelles. The balance between energy intake and energy expenditure controls the body weight gain; while all the organs in our body have their own metabolic feature. Each organ contains several kinds of cell types with different metabolism, and tumor is also famous for its metabolic heterogeneity. Even within the cells, all kinds of nutrient are used to provide the support for basic cellular activities, including survival, mobility and growth.
A major goal of my research is to explore the coordinated metabolic adaptation under both normal physiological and specific pathological conditions. Metabolic reactions have their spatial and temporal distribution, which is also known as cellular compartmentation. A wide variety of cell types present in both the adipose tissue of diabetic patients and the tumor of cancer patients, and their metabolism actively communicates with each other, which is another layer of compartmentation. Metabolites, like citrate and serine, are well known for their nutrient role, and they can also serve as signal molecule between the cells and within the subcellular structure. My recent study showed that a novel cytosol-to-mitochondria citrate transport system mitigates the mitochondrial oxidative stress in the detached cancer cell, and we will look into the signaling control between the subcellular organelles.
With the aim of precision medicine, biology becomes a data-rich science. While the genetic heterogeneity is widely accepted with the easy access to the large sequencing data, the metabolic heterogeneity has also been more appreciated with the evolution of the analytical tools. The integration of mass spec based metabolic tracing and mathematical bioengineering based modeling prediction will provide a new angle to understand the metabolic rewiring in diabetes, cancer and other diseases. A better knowledge of the central carbon metabolism, amino acid utilization and nucleic acid synthesis will lead to new diagnostic approach and potential novel drug target.
2015, Travel Award for Poster Presentation, UTSW, Dallas, TX
2009, Unilever Scholarship, China
2009, Chinese Academy of Sciences Dean Award, China
2008, Merit student, Chinese Academy of Sciences, China
2017-present, American Diabetes Association
2015-present, American Association for Cancer Research
- Jiang L, Boufersaoui A, Yang C, Ko B, Rakheja D, Guevara G, Hu Z, DeBerardinis RJ. Quantitative metabolic flux analysis reveals an unconventional pathway of fatty acid synthesis in cancer cells deficient for the mitochondrial citrate transport protein. Metab Eng. 2017
- Jiang L, Shestov AA, Swain P, Yang C, Parker SJ, Wang QA, Terada LS, Adams ND, McCabe MT, Pietrak B, Schmidt S, Metallo CM, Dranka BP, Schwartz B, DeBerardinis RJ. Reductive carboxylation supports redox homeostasis during anchorage-independent growth. Nature. 2016
- Jiang L, Xiao L, Sugiura H, Huang X, Ali A, Kuro-o M, Deberardinis RJ, Boothman DA. Metabolic reprogramming during TGFβ1-induced epithelial-to-mesenchymal transition. Oncogene. 2015
- Schell JC, Olson KA, Jiang L, Hawkins AJ, Van Vranken JG, Xie J, Egnatchik RA, Earl EG, DeBerardinis RJ, Rutter J. A role for the mitochondrial pyruvate carrier as a repressor of the Warburg effect and colon cancer cell growth. Mol Cell. 2014
- Yang C, Ko B, Hensley CT, Jiang L, Wasti AT, Kim J, Sudderth J, Calvaruso MA, Lumata L, Mitsche M, Rutter J, Merritt ME, DeBerardinis RJ. Glutamine oxidation maintains the TCA cycle and cell survival during impaired mitochondrial pyruvate transport. Mol Cell. 2014
To view more of Lei Jiang's publications, please visit the NCBI link here.
Lab Publications
- Wang Z, Wang QA, Liu Y, Jiang L. Energy metabolism in brown adipose tissue. FEBS J. 2021 Jun;288(12):3647-3662. doi: 10.1111/febs.16015. Epub 2021 May 24. Review. PubMed PMID: 34028971.
- Qing Y, Dong L, Gao L, Li C, Li Y, Han L, Prince E, Tan B, Deng X, Wetzel C, Shen C, Gao M, Chen Z, Li W, Zhang B, Braas D, Ten Hoeve J, Sanchez GJ, Chen H, Chan LN, Chen CW, Ann D, Jiang L, Müschen M, Marcucci G, Plas DR, Li Z, Su R, Chen J. R-2-hydroxyglutarate attenuates aerobic glycolysis in leukemia by targeting the FTO/m6A/PFKP/LDHB axis. Mol Cell. 2021 Mar 4;81(5):922-939.e9. doi: 10.1016/j.molcel.2020.12.026. PubMed PMID: 33434505; PubMed Central PMCID: PMC7935770.
- Wang Z, Ning T, Song A, Rutter J, Wang QA, Jiang L. Chronic cold exposure enhances glucose oxidation in brown adipose tissue. EMBO Rep. 2020 Nov 5;21(11):e50085. doi: 10.15252/embr.202050085. Epub 2020 Oct 12. PubMed PMID: 33043581; PubMed Central PMCID: PMC7645266.
- Dai W, Wang G, Chwa J, Oh ME, Abeywardana T, Yang Y, Wang QA, Jiang L. Mitochondrial division inhibitor (mdivi-1) decreases oxidative metabolism in cancer. Br J Cancer. 2020 Apr;122(9):1288-1297. doi: 10.1038/s41416-020-0778-x. Epub 2020 Mar 9. PubMed PMID: 32147668; PubMed Central PMCID: PMC7188673.
- Song A, Dai W, Jang MJ, Medrano L, Li Z, Zhao H, Shao M, Tan J, Li A, Ning T, Miller MM, Armstrong B, Huss JM, Zhu Y, Liu Y, Gradinaru V, Wu X, Jiang L, Scherer PE, Wang QA. Low- and high-thermogenic brown adipocyte subpopulations coexist in murine adipose tissue. J Clin Invest. 2020 Jan 2;130(1):247-257. doi: 10.1172/JCI129167. PubMed PMID: 31573981; PubMed Central PMCID: PMC6934193.
- Dai W, Jiang L. Dysregulated Mitochondrial Dynamics and Metabolism in Obesity, Diabetes, and Cancer. Front Endocrinol (Lausanne). 2019;10:570. doi: 10.3389/fendo.2019.00570. eCollection 2019. Review. PubMed PMID: 31551926; PubMed Central PMCID: PMC6734166.
- Ni M, Solmonson A, Pan C, Yang C, Li D, Notzon A, Cai L, Guevara G, Zacharias LG, Faubert B, Vu HS, Jiang L, Ko B, Morales NM, Pei J, Vale G, Rakheja D, Grishin NV, McDonald JG, Gotway GK, McNutt MC, Pascual JM, DeBerardinis RJ. Functional Assessment of Lipoyltransferase-1 Deficiency in Cells, Mice, and Humans. Cell Rep. 2019 Apr 30;27(5):1376-1386.e6. doi: 10.1016/j.celrep.2019.04.005. PubMed PMID: 31042466; PubMed Central PMCID: PMC7351313.
- Cheng CT, Qi Y, Wang YC, Chi KK, Chung Y, Ouyang C, Chen YR, Oh ME, Sheng X, Tang Y, Liu YR, Lin HH, Kuo CY, Schones D, Vidal CM, Chu JC, Wang HJ, Chen YH, Miller KM, Chu P, Yen Y, Jiang L, Kung HJ, Ann DK. Arginine starvation kills tumor cells through aspartate exhaustion and mitochondrial dysfunction. Commun Biol. 2018;1:178. doi: 10.1038/s42003-018-0178-4. eCollection 2018. PubMed PMID: 30393775; PubMed Central PMCID: PMC6203837.
- Abeywardana T, Oh M, Jiang L, Yang Y, Kong M, Song J, Yang Y. CARM1 suppresses de novo serine synthesis by promoting PKM2 activity. J Biol Chem. 2018 Sep 28;293(39):15290-15303. doi: 10.1074/jbc.RA118.004512. Epub 2018 Aug 21. PubMed PMID: 30131339; PubMed Central PMCID: PMC6166735.
- Wang QA, Song A, Chen W, Schwalie PC, Zhang F, Vishvanath L, Jiang L, Ye R, Shao M, Tao C, Gupta RK, Deplancke B, Scherer PE. Reversible De-differentiation of Mature White Adipocytes into Preadipocyte-like Precursors during Lactation. Cell Metab. 2018 Aug 7;28(2):282-288.e3. doi: 10.1016/j.cmet.2018.05.022. Epub 2018 Jun 14. PubMed PMID: 29909970; PubMed Central PMCID: PMC6535147.
- Wang QA, Zhang F, Jiang L, Ye R, An Y, Shao M, Tao C, Gupta RK, Scherer PE. Peroxisome Proliferator-Activated Receptor γ and Its Role in Adipocyte Homeostasis and Thiazolidinedione-Mediated Insulin Sensitization. Mol Cell Biol. 2018 May 15;38(10). doi: 10.1128/MCB.00677-17. Print 2018 May 15. PubMed PMID: 29483301; PubMed Central PMCID: PMC5954194.
- Hawk MA, Gorsuch CL, Fagan P, Lee C, Kim SE, Hamann JC, Mason JA, Weigel KJ, Tsegaye MA, Shen L, Shuff S, Zuo J, Hu S, Jiang L, Chapman S, Leevy WM, DeBerardinis RJ, Overholtzer M, Schafer ZT. RIPK1-mediated induction of mitophagy compromises the viability of extracellular-matrix-detached cells. Nat Cell Biol. 2018 Mar;20(3):272-284. doi: 10.1038/s41556-018-0034-2. Epub 2018 Feb 19. PubMed PMID: 29459781.
- Simcox J, Geoghegan G, Maschek JA, Bensard CL, Pasquali M, Miao R, Lee S, Jiang L, Huck I, Kershaw EE, Donato AJ, Apte U, Longo N, Rutter J, Schreiber R, Zechner R, Cox J, Villanueva CJ. Global Analysis of Plasma Lipids Identifies Liver-Derived Acylcarnitines as a Fuel Source for Brown Fat Thermogenesis. Cell Metab. 2017 Sep 5;26(3):509-522.e6. doi: 10.1016/j.cmet.2017.08.006. PubMed PMID: 28877455; PubMed Central PMCID: PMC5658052.
- Schell JC, Wisidagama DR, Bensard C, Zhao H, Wei P, Tanner J, Flores A, Mohlman J, Sorensen LK, Earl CS, Olson KA, Miao R, Waller TC, Delker D, Kanth P, Jiang L, DeBerardinis RJ, Bronner MP, Li DY, Cox JE, Christofk HR, Lowry WE, Thummel CS, Rutter J. Control of intestinal stem cell function and proliferation by mitochondrial pyruvate metabolism. Nat Cell Biol. 2017 Sep;19(9):1027-1036. doi: 10.1038/ncb3593. Epub 2017 Aug 14. PubMed PMID: 28812582; PubMed Central PMCID: PMC6137334.
- Jiang L, Boufersaoui A, Yang C, Ko B, Rakheja D, Guevara G, Hu Z, DeBerardinis RJ. Quantitative metabolic flux analysis reveals an unconventional pathway of fatty acid synthesis in cancer cells deficient for the mitochondrial citrate transport protein. Metab Eng. 2017 Sep;43(Pt B):198-207. doi: 10.1016/j.ymben.2016.11.004. Epub 2016 Nov 14. PubMed PMID: 27856334; PubMed Central PMCID: PMC5429990.
- Jiang L, Shestov AA, Swain P, Yang C, Parker SJ, Wang QA, Terada LS, Adams ND, McCabe MT, Pietrak B, Schmidt S, Metallo CM, Dranka BP, Schwartz B, DeBerardinis RJ. Reductive carboxylation supports redox homeostasis during anchorage-independent growth. Nature. 2016 Apr 14;532(7598):255-8. doi: 10.1038/nature17393. Epub 2016 Apr 6. PubMed PMID: 27049945; PubMed Central PMCID: PMC4860952.
- Hensley CT, Faubert B, Yuan Q, Lev-Cohain N, Jin E, Kim J, Jiang L, Ko B, Skelton R, Loudat L, Wodzak M, Klimko C, McMillan E, Butt Y, Ni M, Oliver D, Torrealba J, Malloy CR, Kernstine K, Lenkinski RE, DeBerardinis RJ. Metabolic Heterogeneity in Human Lung Tumors. Cell. 2016 Feb 11;164(4):681-94. doi: 10.1016/j.cell.2015.12.034. Epub 2016 Feb 4. PubMed PMID: 26853473; PubMed Central PMCID: PMC4752889.
- Lin R, Elf S, Shan C, Kang HB, Ji Q, Zhou L, Hitosugi T, Zhang L, Zhang S, Seo JH, Xie J, Tucker M, Gu TL, Sudderth J, Jiang L, Mitsche M, DeBerardinis RJ, Wu S, Li Y, Mao H, Chen PR, Wang D, Chen GZ, Hurwitz SJ, Lonial S, Arellano ML, Khoury HJ, Khuri FR, Lee BH, Lei Q, Brat DJ, Ye K, Boggon TJ, He C, Kang S, Fan J, Chen J. 6-Phosphogluconate dehydrogenase links oxidative PPP, lipogenesis and tumour growth by inhibiting LKB1-AMPK signalling. Nat Cell Biol. 2015 Nov;17(11):1484-96. doi: 10.1038/ncb3255. Epub 2015 Oct 19. Review. PubMed PMID: 26479318; PubMed Central PMCID: PMC4628560.
- Wang QA, Tao C, Jiang L, Shao M, Ye R, Zhu Y, Gordillo R, Ali A, Lian Y, Holland WL, Gupta RK, Scherer PE. Distinct regulatory mechanisms governing embryonic versus adult adipocyte maturation. Nat Cell Biol. 2015 Sep;17(9):1099-111. doi: 10.1038/ncb3217. Epub 2015 Aug 17. PubMed PMID: 26280538; PubMed Central PMCID: PMC4553131.
- Jiang L, Xiao L, Sugiura H, Huang X, Ali A, Kuro-o M, Deberardinis RJ, Boothman DA. Metabolic reprogramming during TGFβ1-induced epithelial-to-mesenchymal transition. Oncogene. 2015 Jul 23;34(30):3908-16. doi: 10.1038/onc.2014.321. Epub 2014 Oct 6. PubMed PMID: 25284588; PubMed Central PMCID: PMC4387121.
- Jiang L, Deberardinis R, Boothman DA. The cancer cell 'energy grid': TGF-β1 signaling coordinates metabolism for migration. Mol Cell Oncol. 2015 Jul-Sep;2(3):e981994. doi: 10.4161/23723556.2014.981994. eCollection 2015 Jul-Sep. PubMed PMID: 27308459; PubMed Central PMCID: PMC4905294.
- Rajagopalan KN, Egnatchik RA, Calvaruso MA, Wasti AT, Padanad MS, Boroughs LK, Ko B, Hensley CT, Acar M, Hu Z, Jiang L, Pascual JM, Scaglioni PP, DeBerardinis RJ. Metabolic plasticity maintains proliferation in pyruvate dehydrogenase deficient cells. Cancer Metab. 2015;3:7. doi: 10.1186/s40170-015-0134-4. eCollection 2015. PubMed PMID: 26137220; PubMed Central PMCID: PMC4487196.
- Yang C, Ko B, Hensley CT, Jiang L, Wasti AT, Kim J, Sudderth J, Calvaruso MA, Lumata L, Mitsche M, Rutter J, Merritt ME, DeBerardinis RJ. Glutamine oxidation maintains the TCA cycle and cell survival during impaired mitochondrial pyruvate transport. Mol Cell. 2014 Nov 6;56(3):414-424. doi: 10.1016/j.molcel.2014.09.025. Epub 2014 Oct 21. PubMed PMID: 25458842; PubMed Central PMCID: PMC4268166.
- Schell JC, Olson KA, Jiang L, Hawkins AJ, Van Vranken JG, Xie J, Egnatchik RA, Earl EG, DeBerardinis RJ, Rutter J. A role for the mitochondrial pyruvate carrier as a repressor of the Warburg effect and colon cancer cell growth. Mol Cell. 2014 Nov 6;56(3):400-413. doi: 10.1016/j.molcel.2014.09.026. Epub 2014 Oct 21. PubMed PMID: 25458841; PubMed Central PMCID: PMC4268416.
- Shan C, Elf S, Ji Q, Kang HB, Zhou L, Hitosugi T, Jin L, Lin R, Zhang L, Seo JH, Xie J, Tucker M, Gu TL, Sudderth J, Jiang L, DeBerardinis RJ, Wu S, Li Y, Mao H, Chen PR, Wang D, Chen GZ, Lonial S, Arellano ML, Khoury HJ, Khuri FR, Lee BH, Brat DJ, Ye K, Boggon TJ, He C, Kang S, Fan J, Chen J. Lysine acetylation activates 6-phosphogluconate dehydrogenase to promote tumor growth. Mol Cell. 2014 Aug 21;55(4):552-65. doi: 10.1016/j.molcel.2014.06.020. Epub 2014 Jul 17. PubMed PMID: 25042803; PubMed Central PMCID: PMC4142084.
- Mullen AR, Hu Z, Shi X, Jiang L, Boroughs LK, Kovacs Z, Boriack R, Rakheja D, Sullivan LB, Linehan WM, Chandel NS, DeBerardinis RJ. Oxidation of alpha-ketoglutarate is required for reductive carboxylation in cancer cells with mitochondrial defects. Cell Rep. 2014 Jun 12;7(5):1679-1690. doi: 10.1016/j.celrep.2014.04.037. Epub 2014 May 22. PubMed PMID: 24857658; PubMed Central PMCID: PMC4057960.
- Zhang Q, Liu B, Cheng Y, Meng Q, Xia T, Jiang L, Chen S, Liu Y, Guo F. Leptin signaling is required for leucine deprivation-enhanced energy expenditure. J Biol Chem. 2014 Jan 17;289(3):1779-87. doi: 10.1074/jbc.M113.528943. Epub 2013 Dec 3. PubMed PMID: 24302741; PubMed Central PMCID: PMC3894354.
- Yang C, Jiang L, Zhang H, Shimoda LA, DeBerardinis RJ, Semenza GL. Analysis of hypoxia-induced metabolic reprogramming. Methods Enzymol. 2014;542:425-55. doi: 10.1016/B978-0-12-416618-9.00022-4. Review. PubMed PMID: 24862279.
- Yu H, Zou Y, Jiang L, Yin Q, He X, Chen L, Zhang Z, Gu W, Li Y. Induction of apoptosis in non-small cell lung cancer by downregulation of MDM2 using pH-responsive PMPC-b-PDPA/siRNA complex nanoparticles. Biomaterials. 2013 Apr;34(11):2738-47. doi: 10.1016/j.biomaterials.2012.12.042. Epub 2013 Jan 24. PubMed PMID: 23352573.
- Jiang L, Deberardinis RJ. Cancer metabolism: When more is less. Nature. 2012 Sep 27;489(7417):511-2. doi: 10.1038/489511a. PubMed PMID: 23018962.
- Mao T, Shao M, Qiu Y, Huang J, Zhang Y, Song B, Wang Q, Jiang L, Liu Y, Han JD, Cao P, Li J, Gao X, Rui L, Qi L, Li W, Liu Y. PKA phosphorylation couples hepatic inositol-requiring enzyme 1alpha to glucagon signaling in glucose metabolism. Proc Natl Acad Sci U S A. 2011 Sep 20;108(38):15852-7. doi: 10.1073/pnas.1107394108. Epub 2011 Sep 12. PubMed PMID: 21911379; PubMed Central PMCID: PMC3179066.
- Wang Q, Li S, Jiang L, Zhou Y, Li Z, Shao M, Li W, Liu Y. Deficiency in hepatic ATP-citrate lyase affects VLDL-triglyceride mobilization and liver fatty acid composition in mice. J Lipid Res. 2010 Sep;51(9):2516-26. doi: 10.1194/jlr.M003335. Epub 2010 May 20. PubMed PMID: 20488800; PubMed Central PMCID: PMC2918436.
- You J, Yu Y, Jiang L, Li W, Yu X, Gonzalez L, Yang G, Ke Z, Li W, Li C, Liu Y. Signaling through Tyr985 of leptin receptor as an age/diet-dependent switch in the regulation of energy balance. Mol Cell Biol. 2010 Apr;30(7):1650-9. doi: 10.1128/MCB.01307-09. Epub 2010 Jan 19. PubMed PMID: 20086094; PubMed Central PMCID: PMC2838075.
- Jiang L, Wang Q, Yu Y, Zhao F, Huang P, Zeng R, Qi RZ, Li W, Liu Y. Leptin contributes to the adaptive responses of mice to high-fat diet intake through suppressing the lipogenic pathway. PLoS One. 2009 Sep 3;4(9):e6884. doi: 10.1371/journal.pone.0006884. PubMed PMID: 19727392; PubMed Central PMCID: PMC2731220.
- Wang Q, Jiang L, Wang J, Li S, Yu Y, You J, Zeng R, Gao X, Rui L, Li W, Liu Y. Abrogation of hepatic ATP-citrate lyase protects against fatty liver and ameliorates hyperglycemia in leptin receptor-deficient mice. Hepatology. 2009 Apr;49(4):1166-75. doi: 10.1002/hep.22774. PubMed PMID: 19177596.
- Jiang L, You J, Yu X, Gonzalez L, Yu Y, Wang Q, Yang G, Li W, Li C, Liu Y. Tyrosine-dependent and -independent actions of leptin receptor in control of energy balance and glucose homeostasis. Proc Natl Acad Sci U S A. 2008 Nov 25;105(47):18619-24. doi: 10.1073/pnas.0804589105. Epub 2008 Nov 17. PubMed PMID: 19015522; PubMed Central PMCID: PMC2587560.
For updates, see our publication list at PubMed.
Key Publications
- A 2016 paper in the journal Nature examined metastasis and how cancer cells survive to reach distant organs after they detach from the extracellular matrix. Providing the first evidence from live cells for a mechanism that had long been hypothesized, Dr. Jiang and colleagues showed that a novel cytosol-to-mitochondria citrate transport system mitigates the mitochondrial oxidative stress in the detached cancer cell, as regulated with the IDH1 pathway.