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Alexander Muir

TitleAssistant Professor
InstitutionUniversity of Chicago
DepartmentBen May Department of Cancer Research
AddressChicago IL 60637
Phone+1 (773) 8346506
Email
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    Our group is interested in understanding the metabolic adaptations that allow cancer cells to grow and proliferate, causing tumor growth. To understand how cancer cell metabolism works to fuel tumor growth, we use metabolomics techniques to catalog what nutrients are in the microenvironment of tumors. This provides us with a "menu" of nutrients that cancer cells could potentially metabolize to fuel their growth. Once we know the "menu" for different tumor types, we then use a variety of experimental tools from metabolomics to CRISPR gene editing to determine which nutrients cancer cells actually consume from the "menu", and which metabolic pathways process these nutrients. From these experiments, we are delineating the biochemical underpinnings of cancer cell growth.
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    Collapse Biography 
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    Massachusetts Institute of Technology, Cambridge, MAPost-doctoral fellow01/2019Tumor Metabolism
    University of California, Berkeley, Berkeley, CAPhD05/2015Biochemistry, Biophysics and Structural Biology
    University of Chicago, Chicago, ILBA/BA06/2009Biology/Romance Languages and Literature

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    R01CA276461     (MUIR, ALEXANDER)Mar 15, 2024 - Feb 28, 2029
    NIH
    Targeting nutrient microenvironment imprinted therapy resistance in pancreatic cancer
    Role: Principal Investigator
    F32CA213810     (MUIR, ALEXANDER)Feb 1, 2017 - Jan 31, 2020
    NIH
    Understanding metabolic pathways that support redox homeostasis in cancer
    Role: Principal Investigator

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    Collapse selected publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
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    PMC Citations indicate the number of times the publication was cited by articles in PubMed Central, and the Altmetric score represents citations in news articles and social media. (Note that publications are often cited in additional ways that are not shown here.) Fields are based on how the National Library of Medicine (NLM) classifies the publication's journal and might not represent the specific topic of the publication. Translation tags are based on the publication type and the MeSH terms NLM assigns to the publication. Some publications (especially newer ones and publications not in PubMed) might not yet be assigned Field or Translation tags.) Click a Field or Translation tag to filter the publications.
    1. Buj R, Cole AR, Danielson J, Xu J, Hurd D, Kishore A, Kedziora KM, Chen J, Yang B, Barras D, Uboveja A, Amalric A, Apiz Saab JJ, Wickramasinghe J, Tangudu NK, Levasseur E, Wang H, Minasyan A, Dadey RE, Sharrow AC, Vendetti FP, Rivadeneira DB, Bakkenist CJ, Delgoffe GM, Hempel N, Snyder NW, Bao R, Soloff AC, Kirkwood JM, Dangaj Laniti D, Kossenkov AV, Muir A, Das J, Davar D, Mesaros C, Aird KM, Kunning S, Bruno TC, Kirk-Wood JM. CDKN2ALow cancer cells outcompete macrophages for microenvironmental zinc to drive immunotherapy resistance. bioRxiv. 2025 Mar 26. PMID: 39975044; PMCID: PMC11839072.
      Citations:    
    2. Hecht F, Zocchi M, Tuttle ET, Ward NP, Smith B, Kang YP, Cazarin J, Soares ZG, Ozgurses ME, Zhao H, Sheehan C, Alimohammadi F, Munger LD, Trivedi D, Asantewaa G, Blick-Nitko SK, Zoeller JJ, Chen Y, Vasiliou V, Turner BM, Muir A, Coloff JL, Munger J, DeNicola GM, Harris IS, Zocchi M, Munger J, Hecht F, Zocchi M, Tuttle ET, Ward NP, Smith B, Kang YP, Cazarin J, Soares ZG, Ozgurses ME, Zhao H, Sheehan C, Alimohammadi F, Munger LD, Trivedi D, Asantewaa G, Blick-Nitko SK, Zoeller JJ, Chen Y, Vasiliou V, Turner BM, Muir A, Coloff JL, Munger J, DeNicola GM, Harris IS. Catabolism of extracellular glutathione supplies amino acids to support tumor growth. bioRxiv. 2024 Oct 13. PMID: 39416022; PMCID: PMC11482906.
      Citations:    
    3. Cognet G, Muir A. Identifying metabolic limitations in the tumor microenvironment. Sci Adv. 2024 Oct 04; 10(40):eadq7305. PMID: 39356752; PMCID: PMC11446263.
      Citations:    Fields:    Translation:HumansAnimals
    4. Yu A, Yesilkanal AE, Thakur A, Wang F, Yang Y, Phillips W, Wu X, Muir A, He X, Spitz F, Yang L. HYENA detects oncogenes activated by distal enhancers in cancer. Nucleic Acids Res. 2024 Sep 09; 52(16):e77. PMID: 39051548; PMCID: PMC11381332.
      Citations:    Fields:    Translation:HumansCells
    5. Jonker PB, Muir A. Metabolic ripple effects - deciphering how lipid metabolism in cancer interfaces with the tumor microenvironment. Dis Model Mech. 2024 Sep 01; 17(9). PMID: 39284708; PMCID: PMC11423921.
      Citations:    Fields:    Translation:HumansAnimals
    6. Tharp KM, Kersten K, Maller O, Timblin GA, Stashko C, Canale FP, Menjivar RE, Hayward MK, Berestjuk I, Ten Hoeve J, Samad B, Ironside AJ, di Magliano MP, Muir A, Geiger R, Combes AJ, Weaver VM. Tumor-associated macrophages restrict CD8+ T cell function through collagen deposition and metabolic reprogramming of the breast cancer microenvironment. Nat Cancer. 2024 Jul; 5(7):1045-1062. PMID: 38831058.
      Citations: 10     Fields:    Translation:HumansAnimalsCells
    7. Abbott KL, Ali A, Reinfeld BI, Deik A, Subudhi S, Landis MD, Hongo RA, Young KL, Kunchok T, Nabel CS, Crowder KD, Kent JR, Madariaga MLL, Jain RK, Beckermann KE, Lewis CA, Clish CB, Muir A, Rathmell WK, Rathmell J, Vander Heiden MG. Metabolite profiling of human renal cell carcinoma reveals tissue-origin dominance in nutrient availability. Elife. 2024 May 24; 13. PMID: 38787918; PMCID: PMC11126308.
      Citations: 2     Fields:    Translation:Humans
    8. Wolf MM, Madden MZ, Arner EN, Bader JE, Ye X, Vlach L, Tigue ML, Landis MD, Jonker PB, Hatem Z, Steiner KK, Gaines DK, Reinfeld BI, Hathaway ES, Xin F, Tantawy MN, Haake SM, Jonasch E, Muir A, Weiss VL, Beckermann KE, Rathmell WK, Rathmell JC. VHL loss reprograms the immune landscape to promote an inflammatory myeloid microenvironment in renal tumorigenesis. J Clin Invest. 2024 Apr 15; 134(8). PMID: 38618956; PMCID: PMC11014672.
      Citations: 1     Fields:    
    9. Yu A, Yesilkanal AE, Thakur A, Wang F, Yang Y, Phillips W, Wu X, Muir A, He X, Spitz F, Yang L. HYENA detects oncogenes activated by distal enhancers in cancer. bioRxiv. 2024 Apr 12. PMID: 38076958; PMCID: PMC10705271.
      Citations:    
    10. Abbott KL, Ali A, Reinfeld BI, Deik A, Subudhi S, Landis MD, Hongo RA, Young KL, Kunchok T, Nabel CS, Crowder KD, Kent JR, Madariaga MLL, Jain RK, Beckermann KE, Lewis CA, Clish CB, Muir A, Rathmell WK, Rathmell JC, Vander Heiden MG. Metabolite profiling of human renal cell carcinoma reveals tissue-origin dominance in nutrient availability. bioRxiv. 2024 Apr 08. PMID: 38187626; PMCID: PMC10769456.
      Citations:    
    11. Hasselluhn MC, Decker-Farrell AR, Vlahos L, Thomas DH, Curiel-Garcia A, Maurer HC, Wasko UN, Tomassoni L, Sastra SA, Palermo CF, Dalton TC, Ma A, Li F, Tolosa EJ, Hibshoosh H, Fernandez-Zapico ME, Muir A, Califano A, Olive KP. Tumor Explants Elucidate a Cascade of Paracrine SHH, WNT, and VEGF Signals Driving Pancreatic Cancer Angiosuppression. Cancer Discov. 2024 Feb 08; 14(2):348-361. PMID: 37966260; PMCID: PMC10922937.
      Citations: 4     Fields:    Translation:HumansAnimalsCells
    12. Fan H, Xia S, Xiang J, Li Y, Ross MO, Lim SA, Yang F, Tu J, Xie L, Dougherty U, Zhang FQ, Zheng Z, Zhang R, Wu R, Dong L, Su R, Chen X, Althaus T, Riedell PA, Jonker PB, Muir A, Lesinski GB, Rafiq S, Dhodapkar MV, Stock W, Odenike O, Patel AA, Opferman J, Tsuji T, Matsuzaki J, Shah H, Faubert B, Elf SE, Layden B, Bissonnette BM, He YY, Kline J, Mao H, Odunsi K, Gao X, Chi H, He C, Chen J. Trans-vaccenic acid reprograms CD8+ T cells and anti-tumour immunity. Nature. 2023 Nov; 623(7989):1034-1043. PMID: 37993715; PMCID: PMC10686835.
      Citations: 17     Fields:    Translation:HumansAnimalsCells
    13. Decker-Farrell AR, Ma A, Li F, Muir A, Olive KP. Generation and ex vivo culture of murine and human pancreatic ductal adenocarcinoma tissue slice explants. STAR Protoc. 2023 Dec 15; 4(4):102711. PMID: 37950862; PMCID: PMC10682255.
      Citations: 2     Fields:    Translation:HumansAnimals
    14. Meliton AY, Cetin-Atalay R, Tian Y, Szafran JCH, Shin KWD, Cho T, Sun KA, Woods PS, Shamaa OR, Chen B, Muir A, Mutlu GM, Hamanaka RB. Mitochondrial One-Carbon Metabolism is Required for TGF-ß-Induced Glycine Synthesis and Collagen Protein Production. bioRxiv. 2023 Nov 07. PMID: 37986788; PMCID: PMC10659399.
      Citations:    
    15. Abbott KL, Ali A, Casalena D, Do BT, Ferreira R, Cheah JH, Soule CK, Deik A, Kunchok T, Schmidt DR, Renner S, Honeder SE, Wu M, Chan SH, Tseyang T, Stoltzfus AT, Michel SLJ, Greaves D, Hsu PP, Ng CW, Zhang CJ, Farsidjani A, Kent JR, Madariaga MLL, Gramatikov IMT, Matheson NJ, Lewis CA, Clish CB, Rees MG, Roth JA, Griner LM, Muir A, Auld DS, Vander Heiden MG. Screening in serum-derived medium reveals differential response to compounds targeting metabolism. Cell Chem Biol. 2023 09 21; 30(9):1156-1168.e7. PMID: 37689063; PMCID: PMC10581593.
      Citations: 8     Fields:    Translation:HumansCells
    16. Apiz Saab JJ, Muir A. Tumor interstitial fluid analysis enables the study of microenvironment-cell interactions in cancers. Curr Opin Biotechnol. 2023 10; 83:102970. PMID: 37494818; PMCID: PMC10528471.
      Citations: 3     Fields:    Translation:HumansCells
    17. Apiz Saab JJ, Dzierozynski LN, Jonker PB, AminiTabrizi R, Shah H, Menjivar RE, Scott AJ, Nwosu ZC, Zhu Z, Chen RN, Oh M, Sheehan C, Wahl DR, Pasca di Magliano M, Lyssiotis CA, Macleod KF, Weber CR, Muir A. Pancreatic tumors exhibit myeloid-driven amino acid stress and upregulate arginine biosynthesis. Elife. 2023 05 31; 12. PMID: 37254839; PMCID: PMC10260022.
      Citations: 13     Fields:    Translation:AnimalsCells
    18. Nwosu ZC, Ward MH, Sajjakulnukit P, Poudel P, Ragulan C, Kasperek S, Radyk M, Sutton D, Menjivar RE, Andren A, Apiz-Saab JJ, Tolstyka Z, Brown K, Lee HJ, Dzierozynski LN, He X, Ps H, Ugras J, Nyamundanda G, Zhang L, Halbrook CJ, Carpenter ES, Shi J, Shriver LP, Patti GJ, Muir A, Pasca di Magliano M, Sadanandam A, Lyssiotis CA. Uridine-derived ribose fuels glucose-restricted pancreatic cancer. Nature. 2023 Jun; 618(7963):151-158. PMID: 37198494; PMCID: PMC10232363.
      Citations: 34     Fields:    Translation:HumansAnimalsCells
    19. Abbott KL, Ali A, Casalena D, Do BT, Ferreira R, Cheah JH, Soule CK, Deik A, Kunchok T, Schmidt DR, Renner S, Honeder SE, Wu M, Chan SH, Tseyang T, Greaves D, Hsu PP, Ng CW, Zhang CJ, Farsidjani A, Gramatikov IMT, Matheson NJ, Lewis CA, Clish CB, Rees MG, Roth JA, Griner LM, Muir A, Auld DS, Heiden MGV. Screening in serum-derived medium reveals differential response to compounds targeting metabolism. bioRxiv. 2023 Feb 27. PMID: 36909640; PMCID: PMC10002634.
      Citations:    
    20. Sullivan MR, McGowen K, Liu Q, Akusobi C, Young DC, Mayfield JA, Raman S, Wolf ID, Moody DB, Aldrich CC, Muir A, Rubin EJ. Biotin-dependent cell envelope remodelling is required for Mycobacterium abscessus survival in lung infection. Nat Microbiol. 2023 03; 8(3):481-497. PMID: 36658396; PMCID: PMC9992005.
      Citations: 6     Fields:    Translation:HumansCells
    21. Sheehan C, Muir A. The requirement for mitochondrial respiration in cancer varies with disease stage. PLoS Biol. 2022 09; 20(9):e3001800. PMID: 36149877; PMCID: PMC9506606.
      Citations: 4     Fields:    Translation:HumansCells
    22. Sela Y, Li J, Maheswaran S, Norgard R, Yuan S, Hubbi M, Doepner M, Xu JP, Ho ES, Mesaros C, Sheehan C, Croley G, Muir A, Blair IA, Shalem O, Dang CV, Stanger BZ. Bcl-xL Enforces a Slow-Cycling State Necessary for Survival in the Nutrient-Deprived Microenvironment of Pancreatic Cancer. Cancer Res. 2022 05 16; 82(10):1890-1908. PMID: 35315913; PMCID: PMC9117449.
      Citations: 4     Fields:    Translation:HumansCells
    23. Reinfeld BI, Madden MZ, Wolf MM, Chytil A, Bader JE, Patterson AR, Sugiura A, Cohen AS, Ali A, Do BT, Muir A, Lewis CA, Hongo RA, Young KL, Brown RE, Todd VM, Huffstater T, Abraham A, O'Neil RT, Wilson MH, Xin F, Tantawy MN, Merryman WD, Johnson RW, Williams CS, Mason EF, Mason FM, Beckermann KE, Vander Heiden MG, Manning HC, Rathmell JC, Rathmell WK. Cell-programmed nutrient partitioning in the tumour microenvironment. Nature. 2021 05; 593(7858):282-288. PMID: 33828302; PMCID: PMC8122068.
      Citations: 349     Fields:    
    24. Badeaux MD, Rolig AS, Agnello G, Enzler D, Kasiewicz MJ, Priddy L, Wiggins JF, Muir A, Sullivan MR, Van Cleef J, Daige C, Vander Heiden MG, Rajamanickam V, Wooldridge JE, Redmond WL, Rowlinson SW. Arginase Therapy Combines Effectively with Immune Checkpoint Blockade or Agonist Anti-OX40 Immunotherapy to Control Tumor Growth. Cancer Immunol Res. 2021 04; 9(4):415-429. PMID: 33500272.
      Citations: 10     Fields:    Translation:HumansAnimalsCells
    25. Francescone R, Franco-Barraza J, Wagner J, Muir A, Lau AN, Gabitova L, Pazina T, Gupta S, Luong T, Rollins D, Malik R, Thapa RJ, Restifo D, Zhou Y, Cai KQ, Hensley HH, Tan Y, Kruger WD, Devarajan K, Balachandran S, Klein-Szanto AJ, Wang H, El-Deiry WS, Vander Heiden MG, Peri S, Campbell KS, Astsaturov I, Cukierman E, Barbosa Vendramini-Costa D. Netrin G1 Promotes Pancreatic Tumorigenesis through Cancer-Associated Fibroblast-Driven Nutritional Support and Immunosuppression. Cancer Discov. 2021 02; 11(2):446-479. PMID: 33127842; PMCID: PMC7858242.
      Citations: 70     Fields:    Translation:Humans
    26. Romero R, Westcott PMK, Mercer KL, Bhutkar A, Muir A, Liao LZ, Ng SR, Li L, Naranjo S, Beytagh MC, Lewis CA, Hsu PP, Bronson RT, Vander Heiden MG, Jacks T, Sánchez-Rivera FJ, González Robles TJ, Rodríguez SL, Colón CI. Publisher Correction: Keap1 mutation renders lung adenocarcinomas dependent on Slc33a1. Nat Cancer. 2020 Sep; 1(9):935. PMID: 35121957.
      Citations:    Fields:    
    27. Romero R, Westcott PMK, Mercer KL, Bhutkar A, Muir A, Liao LZ, Ng SR, Li L, Naranjo S, Beytagh MC, Lewis CA, Hsu PP, Bronson RT, Vander Heiden MG, Jacks T, Sánchez-Rivera FJ, González Robles TJ, Lamboy Rodríguez S, Colón CI. Keap1 mutation renders lung adenocarcinomas dependent on Slc33a1. Nat Cancer. 2020 06; 1(6):589-602. PMID: 34414377; PMCID: PMC8373048.
      Citations: 27     Fields:    Translation:HumansAnimals
    28. Sullivan MR, Lewis CA, Muir A. Isolation and Quantification of Metabolite Levels in Murine Tumor Interstitial Fluid by LC/MS. Bio Protoc. 2019 Nov 20; 9(22):e3427. PMID: 33654924; PMCID: PMC7853983.
      Citations: 3     
    29. Sullivan MR, Danai LV, Lewis CA, Chan SH, Gui DY, Kunchok T, Dennstedt EA, Vander Heiden MG, Muir A. Quantification of microenvironmental metabolites in murine cancers reveals determinants of tumor nutrient availability. Elife. 2019 04 16; 8. PMID: 30990168; PMCID: PMC6510537.
      Citations: 244     Fields:    Translation:AnimalsCells
    30. Sullivan MR, Mattaini KR, Dennstedt EA, Nguyen AA, Sivanand S, Reilly MF, Meeth K, Muir A, Darnell AM, Bosenberg MW, Lewis CA, Vander Heiden MG. Increased Serine Synthesis Provides an Advantage for Tumors Arising in Tissues Where Serine Levels Are Limiting. Cell Metab. 2019 06 04; 29(6):1410-1421.e4. PMID: 30905671; PMCID: PMC6551255.
      Citations: 122     Fields:    Translation:HumansAnimalsCells
    31. Muir A, Danai LV, Vander Heiden MG. Microenvironmental regulation of cancer cell metabolism: implications for experimental design and translational studies. Dis Model Mech. 2018 08 07; 11(8). PMID: 30104199; PMCID: PMC6124553.
      Citations: 60     Fields:    Translation:HumansAnimals
    32. Chauhan N, Muir A, Davis JC, Menon AK, Levine TP, Thorner J, Roelants FM. TOR complex 2-regulated protein kinase Ypk1 controls sterol distribution by inhibiting StARkin domain-containing proteins located at plasma membrane-endoplasmic reticulum contact sites. Mol Biol Cell. 2018 08 15; 29(17):2128-2136. PMID: 29927351; PMCID: PMC6232965.
      Citations: 16     Fields:    Translation:AnimalsCells
    33. Danai LV, Babic A, Rosenthal MH, Dennstedt EA, Muir A, Lien EC, Mayers JR, Tai K, Lau AN, Jones-Sali P, Prado CM, Petersen GM, Takahashi N, Sugimoto M, Yeh JJ, Lopez N, Bardeesy N, Fernandez-Del Castillo C, Liss AS, Koong AC, Bui J, Yuan C, Welch MW, Brais LK, Kulke MH, Dennis C, Clish CB, Wolpin BM, Vander Heiden MG. Altered exocrine function can drive adipose wasting in early pancreatic cancer. Nature. 2018 06; 558(7711):600-604. PMID: 29925948; PMCID: PMC6112987.
      Citations: 69     Fields:    Translation:Animals
    34. Muir A, Vander Heiden MG. The nutrient environment affects therapy. Science. 2018 06 01; 360(6392):962-963. PMID: 29853672; PMCID: PMC6368963.
      Citations: 64     Fields:    Translation:Humans
    35. Sayin VI, LeBoeuf SE, Singh SX, Davidson SM, Biancur D, Guzelhan BS, Alvarez SW, Wu WL, Karakousi TR, Zavitsanou AM, Ubriaco J, Muir A, Karagiannis D, Morris PJ, Thomas CJ, Possemato R, Vander Heiden MG, Papagiannakopoulos T. Activation of the NRF2 antioxidant program generates an imbalance in central carbon metabolism in cancer. Elife. 2017 10 02; 6. PMID: 28967864; PMCID: PMC5624783.
      Citations: 121     Fields:    Translation:HumansAnimalsCells
    36. Muir A, Danai LV, Gui DY, Waingarten CY, Lewis CA, Vander Heiden MG. Environmental cystine drives glutamine anaplerosis and sensitizes cancer cells to glutaminase inhibition. Elife. 2017 08 15; 6. PMID: 28826492; PMCID: PMC5589418.
      Citations: 173     Fields:    Translation:HumansAnimalsCells
    37. Leskoske KL, Pedersen RTA, Muir A, Liu JM, Finnigan GC, Thorner J, Roelants FM. TOR Complex 2-Regulated Protein Kinase Fpk1 Stimulates Endocytosis via Inhibition of Ark1/Prk1-Related Protein Kinase Akl1 in Saccharomyces cerevisiae. Mol Cell Biol. 2017 04 01; 37(7). PMID: 28069741; PMCID: PMC5359421.
      Citations: 21     Fields:    Translation:AnimalsCells
    38. Muir A, Ramachandran S, Thorner J, Guerreiro JF, Sá-Correia I. Sphingolipid biosynthesis upregulation by TOR complex 2-Ypk1 signaling during yeast adaptive response to acetic acid stress. Biochem J. 2016 Dec 01; 473(23):4311-4325. PMID: 27671892; PMCID: PMC5124397.
      Citations: 29     Fields:    Translation:AnimalsCells
    39. Mayers JR, Torrence ME, Danai LV, Papagiannakopoulos T, Davidson SM, Bauer MR, Lau AN, Ji BW, Dixit PD, Hosios AM, Muir A, Chin CR, Freinkman E, Jacks T, Wolpin BM, Vitkup D, Vander Heiden MG. Tissue of origin dictates branched-chain amino acid metabolism in mutant Kras-driven cancers. Science. 2016 09 09; 353(6304):1161-5. PMID: 27609895; PMCID: PMC5245791.
      Citations: 305     Fields:    Translation:HumansAnimals
    40. Muir A, Timmons G, Leskoske KL, Thorner J, Roelants FM. Down-regulation of TORC2-Ypk1 signaling promotes MAPK-independent survival under hyperosmotic stress. Elife. 2015 Aug 14; 4. PMID: 26274562; PMCID: PMC4552222.
      Citations: 30     Fields:    Translation:AnimalsCells
    41. Muir A, Ramachandran S, Timmons G, Thorner J, Roelants FM. TORC2-dependent protein kinase Ypk1 phosphorylates ceramide synthase to stimulate synthesis of complex sphingolipids. Elife. 2014 Oct 03; 3. PMID: 25279700; PMCID: PMC4217029.
      Citations: 92     Fields:    Translation:AnimalsCells
    42. Breslow DK, Muir A, Weissman JS, Thorner J, Roelants FM. Protein kinase Ypk1 phosphorylates regulatory proteins Orm1 and Orm2 to control sphingolipid homeostasis in Saccharomyces cerevisiae. Proc Natl Acad Sci U S A. 2011 Nov 29; 108(48):19222-7. PMID: 22080611; PMCID: PMC3228448.
      Citations: 159     Fields:    Translation:AnimalsCells
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