Brent

Stockwell

Brent Stockwell is pictured
Professor
1208 NWC Building, 550 West 120th Street, M.C. 4846
New York
NY
10027
Office Phone: 
(212) 854-2948
Lab Phone: 
(212) 854-2899
Fax: 
(212) 854-3293
Short Research Description: 

Diagramming disease networks with chemical and biological tools.

Full Research Description: 

We are using chemical and biological tools to study ferroptosis, a form of regulated cell death discovered in the Stockwell Lab. Ferroptosis is an iron-dependent form of oxidative, non-apoptotic cell death that is tightly linked to metabolism and disease.

We are exploring how ferroptosis in triggered during normal physiological processes and in disease states, and how it can be induced and inhibited for therapeutic benefit in various cancers and neurodegenerative diseases.

We use synthetic organic chemistry and computational chemistry tools to design chemical probes and drug candidates that reveal cellular and molecular mechanisms.  We also use metabolomics, lipidomics, mass spectrometry imaging, CRISPR and siRNA/shRNA screening, protein expression and biochemistry, structure elucidation and animal models of disease to explore these questions.

Representative Publications: 
  • Herman AG, Hayano M, Poyurovsky MV, Shimada K, Skouta R, Prives C, Stockwell BR. (2011 Jul) Discovery of Mdm2-MdmX E3 Ligase Inhibitors Using a Cell-Based Ubiquitination Assay. Cancer Discov
  • Bauer AJ, Gieschler S, Lemberg KM, McDermott AE, Stockwell BR. (2011 Apr) Functional Model of Metabolite Gating by Human Voltage-Dependent Anion Channel 2 Biochemistry
  • Hoffstrom BG, Kaplan A, Letso R, Schmid RS, Turmel GJ, Lo DC, Stockwell BR. (2010 Dec) Inhibitors of protein disulfide isomerase suppress apoptosis induced by misfolded proteins. Nat Chem Biol
  • Varma H, Yamamoto A, Sarantos MR, Hughes RE, Stockwell BR. (2010 Sep) Mutant Huntingtin Alters Cell Fate in Response to Microtubule Depolymerization via GEF-H1-RhoA-ERK Pathway. J Biol Chem
  • Welsch ME, Snyder SA, Stockwell BR. (2010 Jun) Privileged scaffolds for library design and drug discovery. Curr Opin Chem Biol 14(3): 347-361.
  • Dixon SJ, Stockwell BR. (2009 Dec) Identifying druggable disease-modifying gene products. Curr Opin Chem Biol 13(5-6): 549-555.
  • Gangadhar NM, Firestein SJ, Stockwell BR. (2008 Aug) A novel role for jun N-terminal Kinase signaling in olfactory sensory neuronal death. Mol Cell Neurosci 38(4): 518-525.
  • Yang WS, Stockwell BR. (2008 Jun) Inhibition of casein kinase 1-epsilon induces cancer-cell-selective, PERIOD2-dependent growth arrest. Genome Biology 9(6) Epub 2008 Jun: R92.
  • Bauer AJ, Stockwell BR. (2008 Mar) Neurobiological Applications of Small Molecule Screening Chemical Reviews 108(5): 1774–1786..
  • Yang WS, Stockwell BR. (2008 Mar) Synthetic Lethal Screening Identifies Compounds Activating Iron-Dependent, Nonapoptotic Cell Death in Oncogenic-RAS-Harboring Cancer Cells. Chemistry & Biology 15(3): 234-245.
  • Varma H, Lo DC, Stockwell BR. (2008 Mar) activating iron-dependent, nonapoptotic cell death in oncogenic-RAS-harboring Comb Chem High Throughput Screen 11(3): 238-248.
  • Yagoda N, von Rechenberg M, Zaganjor E, Bauer AJ, Yang WS, Fridman DJ, Wolpaw AJ, Smukste I, Peltier JM, Boniface JJ, Smith R, Lessnick SL, Sahasrabudhe S, Stockwell BR. (2007 Jun 14) RAS-RAF-MEK-dependent oxidative cell death involving voltage-dependent anion channels. Nature 447: (7146):865-9.
  • Voisine C, Varma H, Walker N, Bates EA, Stockwell BR, Hart AC. (2007 Jun 6) Identification of Potential Therapeutic Drugs for Huntington's Disease using Caenorhabditis elegans. PLoS ONE 2: e504.
  • Lehar J, Zimmermann GR, Krueger AS, Molnar RA, Ledell JT, Heilbut AM, Short GF 3rd, Giusti LC, Nolan GP, Magid OA, Lee MS, Borisy AA, Stockwell BR, Keith CT. (2007) Chemical combination effects predict connectivity in biological systems. Mol Syst Biol. 3: 0..
  • Varma H, Voisine C, DeMarco CT, Cattaneo E, Lo DC, Hart AC, Stockwell BR. (2007 Feb) Abstract Selective inhibitors of death in mutant huntingtin cells. Nat Chem Biol. 3(2): 99-100.
  • Moffat J, Grueneberg DA, Yang X, Kim SY, Kloepfer AM, Hinkle G, Piqani B, Eisenhaure TM, Luo B, Grenier JK, Carpenter AE, Foo SY, Stewart SA, Stockwell BR, Hacohen N, Hahn WC, Lander ES, Sabatini DM, Root DE. (2006 Mar 24) A lentiviral RNAi library for human and mouse genes applied to an arrayed viral high-content screen. Cell 124(6): 1283-98.
  • Moffat J, Grueneberg DA, Yang X, Kim SY, Kloepfer AM, Hinkle G, Piqani B, Eisenhaure TM, Luo B, Grenier JK, Carpenter AE, Foo SY, Stewart SA, Stockwell BR, Hacohen N, Hahn WC, Lander ES, Sabatini DM, Root DE. (2006 Mar 24) A lentiviral RNAi library for human and mouse genes applied to an arrayed viral high-content screen. Cell 124(6): 1283-98.
  • Smukste I, Bhalala O, Persico M, Stockwell BR. (2006 Feb) Using small molecules to overcome drug resistance induced by a viral oncogene. Cancer Cell. 9(2): 133-46.
  • Lunn MR, Stockwell BR. (2005 Oct) Chemical genetics and orphan genetic diseases. Chem Biol. 12(10): 1063-73.
  • Smukste I, Stockwell BR. (2005) Advances in chemical genetics. Annu Rev Genomics Hum Genet. 3: 261-86.
  • Stockwell BR. (004 Dec 16) Exploring biology with small organic molecules. Nature 432(7019): 846-54.
  • Kelley BP, Lunn MR, Root DE, Flaherty SP, Martino AM, Stockwell BR. (2004 Nov) A flexible data analysis tool for chemical genetic screens. Chem Biol. 11(11): 1495-503.
  • Bailey SN, Sabatini DM, Stockwell BR. (2004 Nov 16) Microarrays of small molecules embedded in biodegradable polymers for use in mammalian cell-based screens. Proc Natl Acad Sci U S A 101(46): 16144-9.
  • Kelley BP, Yuan B, Lewitter F, Sharan R, Stockwell BR, Ideker T. (2004 Jul 1) PathBLAST: a tool for alignment of protein interaction networks. Nucleic Acids Res. 32(Web Server issue): W83-8.
  • Stegmaier K, Ross KN, Colavito SA, O'Malley S, Stockwell BR, Golub TR. (2004 Mar) Gene expression-based high-throughput screening(GE-HTS) and application to leukemia differentiation. Nat Genet. 36(3): 257-6.
  • Root DE, Flaherty SP, Kelley BP, Stockwell BR. (2003 Sep) Biological mechanism profiling using an annotated compound library. Chem Biol. 10(9): 881-92.
  • Dolma S, Lessnick SL, Hahn WC, Stockwell BR. (2003 Mar) Identification of genotype-selective antitumor agents using synthetic lethal chemical screening in engineered human tumor cells. Cancer Cell 3(3): 285-96.
  • Stockwell BR. (2000 Nov) Chemical genetics: ligand-based discovery of gene function. Nat Rev Genet. 1(2): 116-25.

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Columbia University
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Columbia University
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biology@columbia.edu
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