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Alexander Muir

Assistant Professor
amuir@uchicago.edu
Websites
Research Summary
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.
Keywords
Metabolism, Cancer of the Pancreas, Cellular Proliferation, Mass Spectrometry, Metabolomics, Cancer Metabolism, Cancer of the Lung
Education
  • Massachusetts Institute of Technology, Cambridge, MA, Post-doctoral fellow Tumor Metabolism 01/2019
  • University of California, Berkeley, Berkeley, CA, PhD Biochemistry, Biophysics and Structural Biology 05/2015
  • University of Chicago, Chicago, IL, BA/BA Biology/Romance Languages and Literature 06/2009
Biosciences Graduate Program Association
Publications

  1. 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 May 16; 82(10):1890-1908. View in: PubMed

  2. Romero R, Sánchez-Rivera FJ, Westcott PMK, Mercer KL, Bhutkar A, Muir A, González Robles TJ, Rodríguez SL, Liao LZ, Ng SR, Li L, Colón CI, Naranjo S, Beytagh MC, Lewis CA, Hsu PP, Bronson RT, Vander Heiden MG, Jacks T. Publisher Correction: Keap1 mutation renders lung adenocarcinomas dependent on Slc33a1. Nat Cancer. 2020 Sep; 1(9):935. View in: PubMed

  3. Romero R, Sánchez-Rivera FJ, Westcott PMK, Mercer KL, Bhutkar A, Muir A, González Robles TJ, Lamboy Rodríguez S, Liao LZ, Ng SR, Li L, Colón CI, Naranjo S, Beytagh MC, Lewis CA, Hsu PP, Bronson RT, Vander Heiden MG, Jacks T. Keap1 mutation renders lung adenocarcinomas dependent on Slc33a1. Nat Cancer. 2020 06; 1(6):589-602. View in: PubMed

  4. 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. View in: PubMed

  5. 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. View in: PubMed

  6. 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. View in: PubMed

  7. Francescone R, Barbosa Vendramini-Costa D, 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. Netrin G1 Promotes Pancreatic Tumorigenesis through Cancer-Associated Fibroblast-Driven Nutritional Support and Immunosuppression. Cancer Discov. 2021 02; 11(2):446-479. View in: PubMed

  8. 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. View in: PubMed

  9. 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. View in: PubMed

  10. 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). View in: PubMed

  11. Roelants FM, Chauhan N, Muir A, Davis JC, Menon AK, Levine TP, Thorner J. 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. View in: PubMed

  12. 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. View in: PubMed

  13. Muir A, Vander Heiden MG. The nutrient environment affects therapy. Science. 2018 06 01; 360(6392):962-963. View in: PubMed

  14. 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. View in: PubMed

  15. 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. View in: PubMed

  16. Roelants FM, Leskoske KL, Pedersen RTA, Muir A, Liu JM, Finnigan GC, Thorner J. 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). View in: PubMed

  17. Guerreiro JF, Muir A, Ramachandran S, Thorner J, 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. View in: PubMed

  18. 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. View in: PubMed

  19. Muir A, Roelants FM, Timmons G, Leskoske KL, Thorner J. Down-regulation of TORC2-Ypk1 signaling promotes MAPK-independent survival under hyperosmotic stress. Elife. 2015 Aug 14; 4. View in: PubMed

  20. Muir A, Ramachandran S, Roelants FM, Timmons G, Thorner J. TORC2-dependent protein kinase Ypk1 phosphorylates ceramide synthase to stimulate synthesis of complex sphingolipids. Elife. 2014 Oct 03; 3. View in: PubMed

  21. Roelants FM, Breslow DK, Muir A, Weissman JS, Thorner J. 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. View in: PubMed
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