Alexander Muir

Assistant Professor
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. Biotin-dependent cell envelope remodelling is required for Mycobacterium abscessus survival in lung infection. Nat Microbiol. 2023 03; 8(3):481-497. View in: PubMed

  2. The requirement for mitochondrial respiration in cancer varies with disease stage. PLoS Biol. 2022 09; 20(9):e3001800. View in: PubMed

  3. 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. View in: PubMed

  4. Publisher Correction: Keap1 mutation renders lung adenocarcinomas dependent on Slc33a1. Nat Cancer. 2020 Sep; 1(9):935. View in: PubMed

  5. Keap1 mutation renders lung adenocarcinomas dependent on Slc33a1. Nat Cancer. 2020 06; 1(6):589-602. View in: PubMed

  6. Cell-programmed nutrient partitioning in the tumour microenvironment. Nature. 2021 05; 593(7858):282-288. View in: PubMed

  7. 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

  8. 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

  9. 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

  10. Quantification of microenvironmental metabolites in murine cancers reveals determinants of tumor nutrient availability. Elife. 2019 04 16; 8. View in: PubMed

  11. 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

  12. Microenvironmental regulation of cancer cell metabolism: implications for experimental design and translational studies. Dis Model Mech. 2018 08 07; 11(8). View in: PubMed

  13. 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

  14. Altered exocrine function can drive adipose wasting in early pancreatic cancer. Nature. 2018 06; 558(7711):600-604. View in: PubMed

  15. The nutrient environment affects therapy. Science. 2018 06 01; 360(6392):962-963. View in: PubMed

  16. Activation of the NRF2 antioxidant program generates an imbalance in central carbon metabolism in cancer. Elife. 2017 10 02; 6. View in: PubMed

  17. Environmental cystine drives glutamine anaplerosis and sensitizes cancer cells to glutaminase inhibition. Elife. 2017 08 15; 6. View in: PubMed

  18. 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

  19. 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

  20. 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

  21. Down-regulation of TORC2-Ypk1 signaling promotes MAPK-independent survival under hyperosmotic stress. Elife. 2015 Aug 14; 4. View in: PubMed

  22. TORC2-dependent protein kinase Ypk1 phosphorylates ceramide synthase to stimulate synthesis of complex sphingolipids. Elife. 2014 Oct 03; 3. View in: PubMed

  23. 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