2025-present  Assistant Professor, Dept. of Biochemistry, Yonsei University, Seoul, Korea 

2019-2025  Postdoctoral Fellow, Princeton University, NJ, USA 

2015-2019  Ph.D. Technion, Israel Institute of Technology, Haifa, Israel 

2013-2015  M.S. Seoul National University, Seoul, Korea

2006-2013 B.S.  Seoul National University, Seoul, Korea 

Our fundamental question:
 Why are eukaryotic organisms – from a single cell to an entire organism – organized into compartments, and how does this compartmentalization shape metabolism in health and disease?

The Won Lee Lab develops and applies fluxomics approaches to uncover how metabolism operates across scales – from subcellular compartments to whole organisms. We pioneered subcellular fluxomics by performing stable isotope tracing in intact cells followed by rapid organelle isolation, metabolomics, and computational modeling, enabling the quantification of compartment-specific fluxes. We later established methods for interorgan and organismal fluxomics, conducting tracer studies in freely moving live animals to map how metabolites flow across tissues and circulation. Having uniquely developed and mastered both of these approaches, our lab is among the very few capable of integrating metabolism seamlessly from the subcellular to the whole-organism level.

A central theme of our work is moving beyond simply cataloging what and how many metabolites are present (metabolomics) toward quantifying what is actively happening in each compartment (spatial fluxomics). By combining stable isotope tracing with spatially resolved analysis, we aim to measure reaction rates in their native subcellular, tissue, and organismal contexts. This framework allows us to ask not just where metabolites are, but how they are used, coordinated, and reprogrammed in health and disease.

Metabolism doesn’t happen uniformly inside a cell – it’s compartmentalized. We have shown that mitochondria, cytosol, and other organelles each run distinct reactions, and their cross-talk often determines whether a cell grows, adapts, or dies (1, 2). Yet our ability to measure metabolism at this level is limited: existing fractionation methods are slow, prone to contamination, and often blur together signals from different compartments. To fully understand how metabolic pathways are wired, we need methods that can deliver rapid, pure, and reproducible subcellular fractions, ideally within a minute, in both cultured cells and tissues. Our lab is developing new tools to meet this need, enabling the first flux-level view of metabolism in real cellular compartments in both in vitro and in vivo, and opening the door to discoveries that bulk analyses have long concealed.

Mitochondria are central hubs that decide whether nutrients are burned for energy, stored, or repurposed for signaling. Our recent work (3) showed that elevated lactate rapidly induces insulin resistance in skeletal muscle and the whole body, revealing that mitochondria don’t just make ATP – they act as gatekeepers of systemic physiology. Yet the molecular logic by which mitochondria sense and respond to their environment in vivo remains poorly understood. This project builds on our discovery to ask: how do mitochondrial metabolic states drive or protect against disease? By mapping mitochondrial function in real time within intact tissues, we aim to uncover how local shifts – like lactate accumulation – scale up to influence whole-body metabolism, with implications for diabetes, cancer, and immunity.

Every tissue lives in its own biochemical “neighborhood,” where local metabolite concentrations shape how cells sense nutrients, communicate, and respond to stress. Yet most of what we know about metabolism comes from blood measurements, homogenized tissue extracts, or cultured cells, which erase the fine-scale differences that define a tissue’s true microenvironment. Without absolute, quantitative data on these local metabolic landscapes, we cannot fully understand how tissues function – or fail – in health and disease. This project aims to establish new approaches for directly measuring metabolite concentrations in intact tissues under physiological conditions, providing the first quantitative maps of metabolic environments across organs. Such measurements will illuminate how tissues coordinate with one another and how disruptions in local environments drive systemic dysfunction, offering a new window into metabolic disease, cancer, and beyond.

Some animals thrive under conditions that would be devastating to humans – tolerating prolonged fasting, extreme cold, or dramatic tissue injury without succumbing to metabolic failure. These examples of “extreme physiology” reveal strategies that evolution has already solved for resilience, repair, and survival. Yet the molecular and metabolic logic behind these adaptations remains largely unexplored. By studying organisms and humans who naturally push the boundaries of physiology, this project seeks to uncover protective metabolic programs that can be translated into new therapeutic concepts. From tissue regeneration to metabolic disease resistance, insights from extreme biology promise to illuminate what is possible for human health.

Language model-guided anticipation and discovery of mammalian metabolites
 Qiang H, Wang F, Lu W, Xing X, Kim H, Mérette SAM, Ayres LB, Oler E, AbuSalim JE, Roichman A, Neinast M, Cordova RA, Lee WD, Herbst E, Gupta V, Neff SL, Hiebert-Giesbrecht M, Young A, Gautam V, Tian S, Wang B, Röst H, Baidwan J, Greiner R, Chen L, Johnston CW, Foster LJ, Shapiro AM, Wishart DS, Rabinowitz JD, Skinnider MA.
 Nature. 2026 Jan 14. doi: 10.1038/s41586-025-09969-x. Online ahead of print.
 PMID: 41535467

Precancer exercise capacity and metabolism during tumor development coordinate the skeletal muscle-tumor metabolic competition
 Leitner BP, Fosam AE, Lee WD, Zilinger K, Nakandakari SCBR, Zhang X, Gaspar RC, Zhu W, Perry CJ, Rabinowitz JD, Perry RJ.
 Proc Natl Acad Sci U S A. 2025 Dec 9;122(49):e2508707122. doi: 10.1073/pnas.2508707122. Epub 2025 Dec 1.
 PMID: 41325517

Nutrient Availability Dictates Cancer Metabolism-Based Therapeutic Responses to Non-oncology Drugs
 Pyun WY, Park JH, Roh JW, Jeon D, Kim J, Paik JE, Cho SC, Park SY, Lim H, Kim H, Jang YJ, Lee J, Byun JH, Son DW, Kim SY, Guan KL, Lee WD, Gee HY, Lee HW, No KT, Choi YS, Hashimoto T, Yoshino T, Jeong HS, Namkung W, Nam JH, Park HW.
 Cancer Res. 2025 Nov 25. doi: 10.1158/0008-5472.CAN-25-1123. Online ahead of print.
 PMID: 41289560

Hepatocyte mitochondrial NAD+ content is limiting for liver regeneration
 Mukherjee S, Velázquez Aponte RA, Perry CE, Lee WD, Janssen KA, Niere M, Adzika GK, Lu MJ, Chan HR, Zou X, Chen B, Bye N, Xiao T, Yook JS, Salik O, Frederick DW, Gaspar RB, Doan KV, Davis JG, Rabinowitz JD, Wallace DC, Snyder NW, Kajimura S, Cambronne XA, Ziegler M, Baur JA.
 Nat Metab. 2025 Nov 20. doi: 10.1038/s42255-025-01408-5. Online ahead of print.
 PMID: 41266821

A tumor-on-a-chip for in vitro study of CAR-T cell immunotherapy in solid tumors
 Liu H, Noguera-Ortega E, Dong X, Lee WD, Chang J, Aydin SA, Li Y, Shin Y, Shi X, Liousia M, Martinez MC, Brotman JJ, Kim S, Chen Z, Wang A, Ou Z, Paek J, Park JY, Liu A, Hu H, Xiao Z, Racca DM, Kim SJ, Worthen GS, Guo W, Puré E, Kang T, Rabinowitz JD, Wherry EJ, Moon EK, Albelda SM, Huh DD.
 Nat Biotechnol. 2025 Oct 17. doi: 10.1038/s41587-025-02845-z. Online ahead of print.
 PMID: 41107533

Spatial metabolic gradients in the liver and small intestine
 Samarah LZ, Zheng C, Xing X, Lee WD, Afriat A, Chitra U, MacArthur MR, Lu W, Jankowski CSR, Ma C, Hunter CJ, Neinast M, Weilandt DR, Raphael BJ, Rabinowitz JD.
 Nature. 2025 Oct 15. doi: 10.1038/s41586-025-09616-5. Online ahead of print.
 PMID: 41094143

Microbiome metabolism of dietary phytochemicals controls the anticancer activity of PI3K inhibitors
 Roichman A, Zuo Q, Hwang S, Lu W, Cordova RA, MacArthur MR, Boyer JA, Mitchell SJ, Powers J, Koval SA, Hunter CJ, Rijmers J, Ryseck RP, AbuSalim JE, Chatterjee S, Lee WD, Xu X, Xing X, Chen Z, Zeng X, Marwaha S, McBride MJ, Guo JY, Kang Y, Donia MS, Rabinowitz JD.
 Cell. 2025 May 29;188(11):3065-3080.e21. doi: 10.1016/j.cell.2025.04.041. Epub 2025 May 19.
 PMID: 40393457

Lactate homeostasis is maintained through regulation of glycolysis and lipolysis
 Lee WD^*, Weilandt DR^*, Liang L, MacArthur MR, Jaiswal N, Ong O, Mann CG, Chu Q, Hunter CJ, Ryseck RP, Lu W, Oschmann AM, Cowan AJ, TeSlaa TA, Bartman CR, Jang C, Baur JA, Titchenell PM, Rabinowitz JD.
 Cell Metab. 2025 Mar 4;37(3):758-771.e8. doi: 10.1016/j.cmet.2024.12.009. Epub 2025 Jan 30.
 PMID: 39889702

Quantification of nutrient fluxes during acute exercise in mice
 Axsom J, TeSlaa T, Lee WD, Chu Q, Cowan A, Bornstein MR, Neinast MD, Bartman CR, Blair MC, Li K, Thorsheim C, Rabinowitz JD, Arany Z.
 Cell Metab. 2024 Dec 3;36(12):2560-2579.e5. doi: 10.1016/j.cmet.2024.09.010. Epub 2024 Oct 15.
 PMID: 39413791

Cardiac NAD+ depletion in mice promotes hypertrophic cardiomyopathy and arrhythmias prior to impaired bioenergetics
 Doan KV, Luongo TS, Ts’olo TT, Lee WD, Frederick DW, Mukherjee S, Adzika GK, Perry CE, Gaspar RB, Walker N, Blair MC, Bye N, Davis JG, Holman CD, Chu Q, Wang L, Rabinowitz JD, Kelly DP, Cappola TP, Margulies KB, Baur JA.
 Nat Cardiovasc Res. 2024 Oct;3(10):1236-1248. doi: 10.1038/s44161-024-00542-9. Epub 2024 Sep 18.
 PMID: 39294272

NAD+ precursors prolong survival and improve cardiac phenotypes in a mouse model of Friedreich’s Ataxia
 Perry CE, Halawani SM, Mukherjee S, Ngaba LV, Lieu M, Lee WD, Davis JG, Adzika GK, Bebenek AN, Bazianos DD, Chen B, Mercado-Ayon E, Flatley LP, Suryawanshi AP, Ho I, Rabinowitz JD, Serai SD, Biko DM, Tamaroff J, DeDio A, Wade K, Lin KY, Livingston DJ, McCormack SE, Lynch DR, Baur JA.
 JCI Insight. 2024 Jul 18;9(16):e177152. doi: 10.1172/jci.insight.177152.
 PMID: 39171530

Selected Ion Monitoring for Orbitrap-Based Metabolomics
 Lu W, McBride MJ, Lee WD, Xing X, Xu X, Li X, Oschmann AM, Shen Y, Bartman C, Rabinowitz JD.
 Metabolites. 2024 Mar 25;14(4):184. doi: 10.3390/metabo14040184.
 PMID: 38668312

mTORC1 controls murine postprandial hepatic glycogen synthesis via Ppp1r3b
 Uehara K, Lee WD, Stefkovich M, Biswas D, Santoleri D, Garcia Whitlock A, Quinn W 3rd, Coopersmith T, Creasy KT, Rader DJ, Sakamoto K, Rabinowitz JD, Titchenell PM.
 J Clin Invest. 2024 Jan 30;134(7):e173782. doi: 10.1172/JCI173782.
 PMID: 38290087

Inferring mitochondrial and cytosolic metabolism by coupling isotope tracing and deconvolution
 Stern A, Fokra M, Sarvin B, Alrahem AA, Lee WD, Aizenshtein E, Sarvin N, Shlomi T.
 Nat Commun. 2023 Nov 18;14(1):7525. doi: 10.1038/s41467-023-42824-z.
 PMID: 37980339

Dichloroacetate as a novel pharmaceutical treatment for cancer-related fatigue in melanoma
 Zhang X, Lee WD, Leitner BP, Zhu W, Fosam A, Li Z, Gaspar RC, Halberstam AA, Robles B, Rabinowitz JD, Perry RJ.
 Am J Physiol Endocrinol Metab. 2023 Oct 1;325(4):E363-E375. doi: 10.1152/ajpendo.00105.2023. Epub 2023 Aug 30.
 PMID: 37646579

Tissue-specific reprogramming of glutamine metabolism maintains tolerance to sepsis
 Leitner BP, Lee WD, Zhu W, Zhang X, Gaspar RC, Li Z, Rabinowitz JD, Perry RJ.
 PLoS One. 2023 Jul 6;18(7):e0286525. doi: 10.1371/journal.pone.0286525. eCollection 2023.
 PMID: 37410734

Impact of acute stress on murine metabolomics and metabolic flux
 Lee WD, Liang L, AbuSalim J, Jankowski CSR, Samarah LZ, Neinast MD, Rabinowitz JD.
 Proc Natl Acad Sci U S A. 2023 May 23;120(21):e2301215120. doi: 10.1073/pnas.2301215120. Epub 2023 May 15.
 PMID: 37186827

Osteoblast-intrinsic defect in glucose metabolism impairs bone formation in type II diabetic male mice
 Song F, Lee WD, Marmo T, Ji X, Song C, Liao X, Seeley R, Yao L, Liu H, Long F.
 Elife. 2023 May 5;12:e85714. doi: 10.7554/eLife.85714.
 PMID: 37144869

Slow TCA flux and ATP production in primary solid tumours but not metastases
 Bartman CR, Weilandt DR, Shen Y, Lee WD, Han Y, TeSlaa T, Jankowski CSR, Samarah L, Park NR, da Silva-Diz V, Aleksandrova M, Gultekin Y, Marishta A, Wang L, Yang L, Roichman A, Bhatt V, Lan T, Hu Z, Xing X, Lu W, Davidson S, Wühr M, Vander Heiden MG, Herranz D, Guo JY, Kang Y, Rabinowitz JD.
 Nature. 2023 Feb;614(7947):349-357. doi: 10.1038/s41586-022-05661-6. Epub 2023 Feb 1.
 PMID: 36725930

Ph.D. Student : 강성현, 권승준, 최선지, 최인경 

Undergraduate Intern : 김민섭, 박성민, 박민혁, 김지석

Homepage :  https://spatialfluxomics.com/

Contact : wdlee@yonsei.ac.kr