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| FACULTY BIOGRAPHY |
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| Brent Stockwell |
| Associate Professor |
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| Lab website
Defining novel cell death pathways involved in cancer
and neurodegeneration
We are discovering novel cell death pathways involved
in cancer and neurodegenerative diseases using chemical and biological tools.
Our approach is to design high-throughput screens in mammalian cells that allow
us to test tens of thousands of small organic molecules and small interfering
RNAs for their ability to affect cellular phenotypes associated with oncogenic
signaling or neurodegeneration. These screens reveal reagents that are used to
identify specific proteins and genes that act as the critical regulators of
cellular disease pathologies. We define the molecular function of these critical
regulators using protein biochemistry, molecular cell biology and chemical
synthesis. Ultimately, we define and validate these pathways in mammalian cells
and in mouse models.
Potential research projects include:
- Elucidating a novel VDAC-mediated cell death
pathway that is selectively lethal to tumor cells
- Discovering novel cell death pathways activated
by mutant huntingtin protein in Huntington Disease
- Expanding the range of druggable target proteins
by creating inhibitors of proteins that are currently considered
undruggable
- Synthesizing privileged small molecule libraries
for screens and for translational research
- Synthesizing and using affinity reagents for
discovering novel target proteins
MedLine Listing of Dr. Stockwell's Publications |
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Representative Recent Publications
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- 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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