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Brent R. Stockwell, Ph.D.
Associate Professor of Biological Sciences and Chemistry
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Research
Summary
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
http://www.columbia.edu/cu/biology/faculty-data/brent-stockwell/faculty.html
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Selected Publications:
1. Kelley BP, Lunn MR, Root DE, Flaherty SP, Martino AM, Stockwell BR. (2004) A flexible data analysis tool for chemical genetic screens. Chem Biol.
11(11):1495-1503
2. Stockwell BR. (2004) Exploring biology with small organic molecules. Nature
432(7019):846-854
3. Smukste I, Stockwell BR. (2005) Advances in chemical genetics. Annu Rev Genomics Hum Genet.
3:261-286
4. Lunn MR, Stockwell BR. (2005) Chemical genetics and orphan genetic diseases. Chem Biol.
12(10):1063-1073
5. Smukste I, Bhalala O, Persico M, Stockwell BR. (2006) Using small molecules to overcome drug resistance induced by a viral oncogene. Cancer Cell
9(2):133-146
6. 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) A lentiviral RNAi library for human and mouse genes applied to an arrayed viral high-content screen. Cell
124(6):1283-1298
7. Varma H, Voisine C, DeMarco CT, Cattaneo E, Lo DC, Hart AC, Stockwell BR. (2007) Abstract Selective inhibitors of death in mutant huntingtin cells. Nat Chem Biol.
3(2):99-100
8. 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.
3:80
9. Voisine C, Varma H, Walker N, Bates EA, Stockwell BR, Hart AC. (2007) Identification of Potential Therapeutic Drugs for Huntington's Disease using Caenorhabditis elegans. PLoS ONE
2:e504
10. 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) RAS-RAF-MEK-dependent oxidative cell death involving voltage-dependent anion channels. Nature
447:(7146):865-869
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