Alexander Muir

Assistant Professor
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. 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 Apr 16; 8. View in: PubMed

  2. 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 Jun 04; 29(6):1410-1421.e4. View in: PubMed

  3. 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

  4. 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

  5. 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

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

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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