Perelman School of Medicine at the University of Pennsylvania

Wellen Lab

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Selected Publications from the Wellen Lab

Soaita I, Megill E, Kantner D, Chatoff A, Cheong YJ, Clarke P, Arany Z, Snyder NW, Wellen KE, Trefely S. Dynamic protein deacetylation is a limited carbon source for acetyl-CoA-dependent metabolism.  J Biol Chem. 2023 May 2:104772. doi: 10.1016/j.jbc.2023.104772. PMID: 37142219 

Izzo LT, Trefely S, Demetriadou C, Drummond JM, Mizukami T, Kuprasertkul N, Farria AT, Nguyen PTT, Murali N, Reich L, Kantner DS, Shaffer J, Affronti H, Carrer A, Andrews A, Capell BC, Snyder NW, Wellen KE. Acetylcarnitine shuttling links mitochondrial metabolism to histone acetylation and lipogenesis. Sci Adv. 2023 May 3;9(18):eadf0115. doi: 10.1126/sciadv.adf0115. PMID: 37134161 

Campbell SL, Mesaros C, Affronti H, Tsang T, Noji M, Sun K, Izzo L, Trefely S, Kruijning S, Blair IA, Wellen KE. Glutamine deprivation triggers NAGK-dependent hexosamine salvage, eLife, 2021 Nov 30; 10:e62644.

Trefely S, Huber K, Liu J Noji M, Stransky S, Singh J, Doan MT, Lovell CD, von Krusenstiern E, Jiang H, Bostwick A, Pepper HL, Izzo L, Zhao Z, Xu JP, Bedi Jr KC, Rame JE, Bogner-Strauss J, Mesaros C, Sidoli S, Wellen KE*, Snyder NW*. Quantitative subcellular acyl-CoA analysis reveals distinct nuclear metabolism and isoleucine-dependent histone propionylation, Mol Cell, 2022 Jan 20;82(2):447-462

Zhao S, Jang C, Liu J, Uehara K, Gilbert M, Izzo L, Zeng X, Trefely S, Fernandez S, Carrer A, Miller KD, Schug ZT, Snyder NW, Gade TP, Titchenell PM, Rabinowitz JD, Wellen KE. Dietary fructose feeds hepatic lipogenesis via microbiota-derived acetate. Nature. 2020 Mar;579(7800):586-591. doi: 10.1038/s41586-020-2101-7.

Trefely S, Liu J, Huber K, Doan MT, Jiang H, Singh J, von Krusenstiern E, Bostwick A, Xu P, Bogner-Strauss JG, Wellen KE, Snyder NW.  Subcellular metabolic pathway kinetics are revealed by correcting for artifactual post harvest metabolism.  Mol Metab. 2019 Dec;30:61-71

Fernandez S, Viola JM, Torres A, Wallace M, Trefely S, Zhao S, Affronti HC, Gengatharan JM, Guertin DA, Snyder NW, Metallo CM, Wellen KE.  Adipocyte ACLY facilitates dietary carbohydrate handling to maintain metabolic homeostasis in females.  Cell Rep, 2019, May 28;27(9):2772-2784.

Carrer A, Trefely S, Zhao S, Campbell SL, Norgard RJ, Schultz KC, Sidoli S, Parris JLD, Affronti HC, Sivanand S, Egolf S, Sela Y, Trizzino M, Gardini A, Garcia BA, Snyder NW, Stanger BZ, Wellen KE.  Acetyl-CoA Metabolism Supports Multistep Pancreatic Tumorigenesis.  Cancer Discov. 2019 Mar;9(3):416-435.

Campbell SL and Wellen KE.  Metabolic Signaling to the Nucleus in Cancer. Mol Cell. 2018 Aug 2;71(3):398-408. 

Lee JV, Berry CT, Kim K, Sen P, Kim T, Carrer A, Trefely S, Zhao S, Fernandez S, Barney LE, Schwartz AD, Peyton SR, Snyder NW, Berger SL, Freedman BD, Wellen KE. Acetyl-CoA promotes glioblastoma cell adhesion and migration through Ca2+-NFAT signaling.  Genes Dev.  2018 Apr 19 [Epub ahead of print]

Sivanand S, Viney I, Wellen KE. Spatiotemporal Control of Acetyl-CoA Metabolism in Chromatin Regulation.  Trends Biochem Sci. 2017 Nov 23. pii: S0968-0004(17)30214-1. doi: 10.1016/j.tibs.2017.11.004. [Epub ahead of print] Review.

Sivanand S, Rhoades S, Jiang Q, Lee JV, Benci J, Zhang J, Yuan S, Viney I, Zhao S, Carrer A, Bennett MJ, Minn AJ, Weljie AM, Greenberg RA, and Wellen KE.  Nuclear Acetyl-CoA Production by ACLY Promotes Homologous Recombination, Mol Cell, 2017 July 6 [Epub ahead of print].

Carrer A, Parris JLD, Trefely S, Henry RA, Montgomery DC, Torres A, Viola JM, Kuo YM, Blair IA, Meier JL, Andrews AJ, Snyder NW, Wellen KE.  Impact of high fat diet on tissue acyl-CoA and histone acetylation levels, J Biol Chem, 2017 Jan 11. [Epub ahead of print].

Zhao S, Torres AM, Henry RA, Trefely T, Wallace M, Lee JV, Carrer A, Sengupta A, Kuo YM, Frey AJ, Meurs N, Viola JM, Blair IA, Weljie A, Snyder NW, Andrews AJ, Wellen KE.  ATP-citrate lyase controls a glucose-to-acetate metabolic switch, Cell Rep, 2016, Oct. 18. PMID: 27760311

Kinnaird A, Zhao S, Wellen KE*, Michelakis ED*.  Metabolic control of epigenetics in cancer.  Nat Rev Cancer, 2016, Sept 16. PMID: 27634449.
Notes: *co-corresponding authors

Shah S, Carriveau WJ, Li J, Campbell SL, Kopinski P, Lim HW, Daurio N, Trefely S, Won KJ, Wallace DC, Koumenis C, Mancuso A, Wellen KE.  Targeting ACLY sensitizes castration-resistant prostate cancer cells to AR antagonism by impinging on an ACLY-AMPK-AR feedback mechanism, Oncotarget, 2016, May 27. PubMed PMID: 27248322.

Carrer A, Wellen KE. Metabolism and epigenetics: a link cancer cells exploit. Current opinion in biotechnology 34: 23-9, August 2015. PMID: 25461508; PMCID: PMC4721608

Lee JV, Carrer A, Shah S, Snyder NW, Wei S, Venneti S, Worth AJ, Yuan ZF, Lim HW, Liu S, Jackson E, Aiello NM, Haas NB, Rebbeck TR, Judkins A, Won KJ, Chodosh LA, Garcia BA, Stanger BZ, Feldman MD, Blair IA, Wellen KE. Akt-dependent metabolic reprogramming regulates tumor cell histone acetylation. Cell Metab. 2014 Aug 5;20(2):306-19. PubMed PMID: 24998913; PubMed Central PMCID: PMC4151270.

LondoƱo Gentile T, Lu C, Lodato PM, Tse S, Olejniczak SH, Witze ES, Thompson CB, Wellen KE. DNMT1 is regulated by ATP-citrate lyase and maintains methylation patterns during adipocyte differentiation. Mol Cell Biol. 2013 Oct;33(19):3864-78. PubMed PMID: 23897429; PubMed Central PMCID: PMC3811875.

Wellen KE, Lu C, Mancuso A, Lemons JM, Ryczko M, Dennis JW, Rabinowitz JD, Coller HA, Thompson CB. The hexosamine biosynthetic pathway couples growth factor-induced glutamine uptake to glucose metabolism. Genes & Development 24(24): 2784-99, December 2010. PMID: 21106670; PMCID: PMC3003197

*Wellen KE, *Hatzivassiliou G, Sachdeva UM, Bui TV, Cross JR, Thompson CB. ATP-citrate lyase links cellular metabolism to histone acetylation. Science 324(5930): 1076-80, May 2009. PMID: 19461003; PMCID: PMC2746744
Notes: *indicates co-first authors

Wellen KE, Fucho R, Gregor MF, Furuhashi M, Morgan C, Lindstad T, Vaillancourt E, Gorgun CZ, Saatcioglu F, Hotamisligil GS. Coordinated regulation of nutrient and inflammatory responses by STAMP2 is essential for metabolic homeostasis. Cell 129(3): 537-48, May 2007. PMID: 17482547; PMCID: PMC2408881

Full List of Wellen KE Publications