Angela N. Koehler
Broad Institute of MIT and Harvard Office: 617-714-7364 Chemical Biology Program Fax: 617-714-8943 7 Cambridge Center Email: [email protected] Cambridge, MA 02142 Website: www.broadinstitute.org/node/2445
Education
Ph.D. Chemistry, Harvard University, 2003 B.A. Biochemistry and Molecular Biology, Reed College, 1997
Research Experience
Investigator, Chemical Biology Program, Broad Institute 2009-present Project & Center Manager, Broad NCI Cancer Target Discovery and Development (CTD2) Center 2010-2012
Institute Fellow, Chemical Biology Program, Broad Institute 2003-2009 Director, Ligand Discovery, NCI Initiative for Chemical Genetics (ICG) at Harvard 2003-2009
Graduate Student, Department of Chemistry and Chemical Biology, Harvard University 1998-2003 Laboratory of Professor Stuart L. Schreiber Thesis: Small molecule microarrays: A high-throughput tool for discovering protein-small molecule interactions
Researcher, Department of Chemistry, California Institute of Technology 1997-1998 Laboratory of Professor Barbara Imperiali Project: Biochemical reconstitution of the oligosaccharyltransferase (OST) complex
Undergraduate Researcher, Department of Chemistry, Reed College 1995-1997 Laboratory of Professor Arthur Glasfeld Co-mentored by Professor Richard G. Brennan at Oregon Health Sciences University Thesis: Biochemical and structural characterization of the tRNA-modifying enzyme QueA from Escherichia coli
Teaching Experience
Research Advisor to postdoctoral fellows, undergraduates, high school students, and staff scientists 2003-present Broad Institute of MIT and Harvard
Instructor, Biochemical Sciences Research (BS91r) 2004-2006, 2010-2011 Harvard University
Associated Instructor, Experimental Research in the Life Sciences (LS100r) 2009 Harvard University
Associated Instructor, Experimental Molecular and Cellular Biology (MCB100) 2004-2006 Harvard University
Teaching Fellow, Chemical Biology (Chem 170) 1999, 2000 Harvard University, Professor David R. Liu
Teaching Fellow, The Organic Chemistry of Life (Chem 27) 1999 Harvard University, Professor Stuart L. Schreiber
Teaching Assistant, Techniques of Experimental Chemistry 1997-1998 Harvard University, Dr. Jane Raymond
Teaching Assistant, Biochemical Methods Laboratory 1997 Reed College, Professor Arthur Glasfeld
Teaching Assistant, General Chemistry Laboratory 1995-1997 Reed College, Professor Ronald W. McClard
Professional Service
Ad Hoc Member of NIH Drug Discovery and Molecular Pharmacology (DMP) Study Section 2012 Ad Hoc Member of NIH Synthetic and Biological Chemistry B (SBCB) Study Section 2011 Advisory Panel, NRC Canada, Genomics and Health Initiative, BioChips Project 2008-2011 Editorial Board, Molecular Diversity (Springer) 2008-2011 Broad Institute Educational Outreach Program Admissions Advisor and Research Mentor 2007-present Intel National Science Talent Search Mentor (Megan Blewett, 7th-place out of 1,700) 2006-2007 HTS Review Board, Broad Institute 2005-present Chembank Steering Committee, NCI Initiative for Chemical Genetics 2005-2006 Technology Platform Committee, Broad Institute 2004-2006
Honors and Awards
Indo-US Frontiers of Science Exchange Award 2011 Kavli Frontiers of Science Scholar, US National Academy of Sciences 2011 Sigma Xi, MIT Chapter 2007-present Eli Lilly Predoctoral Fellowship in Organic Chemistry, Harvard University 2001-2002 MIT 50K Entrepreneur Competition, Finalist 2001 Excellence in Scholarship Award, Reed College 1995-1997 William and Jane Einzig Memorial Scholarship, Reed College 1993-1997 ESCO Undergraduate Scholarship, Reed College 1993-1997
Publications
Broad Institute
1. Izhack Cherny, Maria Korolev, Angela N. Koehler, Michael H. Hecht. “Proteins from an unevolved library of de novo designed sequences bind a range of small molecules.” ACS Synth. Biol., 1, 130-138, 2012. 2. Melissa M. Kemp, Michel Weïwer, Angela N. Koehler.* “Unbiased binding assays for discovering small- molecule probes and drugs.” Bioorg. Med. Chem., 20, 1979-1989, 2012. 3. Dominick E. Casalena, Dina Wassaf, Angela N. Koehler.* “Ligand discovery using small-molecule microarrays.” Chapter, Methods Mol. Biol., 803, 249-263, 2012. 4. Melissa M. Kemp, Qiu Wang, Jason H. Fuller, Nathan West, Nicole Martinez, Elizabeth M. Morse, Michel Weïwer, Stuart L. Schreiber, James E. Bradner, Angela N. Koehler,* “A novel HDAC inhibitor with a hydroxy- pyrimidine scaffold.” Bioorg. Med. Chem. Lett., 21, 4164-4169, 2011. 5. Paul A. Clemons, J. Anthony Wilson, Vlado Dancik, Sandrine Muller, Hyman A. Carrinski, Bridget K. Wagner, Angela N. Koehler, Stuart L. Schreiber. “Quantifying structural property distributions and patterns of performance among sets of small molecules comprising small-molecule screening collections.” Proc. Natl. Acad. Sci. USA, 108, 6817-6822, 2011. 6. Myung-Soo Kang, Eun Kyung Lee, Vishal Soni, Timothy A. Lewis, Angela N. Koehler, Viswanathan Srinivasana, Elliott Kieff. ‘Roscovitine inhibits ENBA1 Serine 393 phosphorylation, nuclear localization, transcription, and episome maintenance.” J. Virol. 85, 2859-2868, 2011. 7. Jermont M. Chen, Anne H. Armstrong, Angela N. Koehler, Michael H. Hecht. “Small-molecule microarrays enable the discovery of compounds that bind the Alzheimer’s Aβ peptide and reduce its cytotoxicity.” J. Am. Chem. Soc., 132, 17015-17022, 2010. This article was featured in the Research Highlights section of Nature Chemistry, November 26 2010. 8. Paul A. Clemons, Nicole E. Bodycombe, Hyman A. Carrinski, J. Anthony Wilson, Alykhan F. Shamji. Bridget K. Wagner, Angela N. Koehler, Stuart L. Schreiber. “Small molecules of different synthetic and natural origins have distinct distributions of structural complexity that correlate with protein-binding profiles.” Proc. Natl. Acad. Sci. USA, 107, 18787-18792, 2010. 9. The Cancer Target Discovery and Development Network: Stuart L. Schreiber, Alykhan F. Shamji, Paul A. Clemons, Cindy Hon, Angela N. Koehler, Benito Munoz, Michelle Palmer, Andrew M. Stern, Bridget K. Wagner, Scott Powers, Scott W. Lowe, Xuecui Guo, Alex Krasnitz, Eric T. Sawey, Raffaella Sordella, Lincoln Stein, Lloyd C. Trotman, Andrea Califano, Riccardo Dalla-Favera, Adolfo Ferrando, Antonio Iavarone, Laura Pasqualucci, José Silva, Brent R. Stockwell, William C. Hahn, Lynda Chin, Ronald A. DePinho, Jesse S. Boehm, Shuba Gopal, Alan Huang, David E. Root, Barbara A. Weir, Daniela S. Gerhard, Jean Claude Zenklusen, Michael G. Roth, Michael A. White, John D. Minna, John B. MacMillan, Bruce A. Posner. “Towards patient-based cancer therapeutics.” Nat. Biotechnol. 28, 904-906, 2010. 10. Angela N. Koehler.* “A complex task? Direct modulation of transcription factors with small molecules.” Curr. Opin. Chem. Biol. 14, Curr. Opin. Chem. Biol., 14, 331-340, 2010. 11. Arturo J. Vegas, Angela N. Koehler.* “Detecting protein-small molecule interactions using fluorous small- molecule microarrays.” Methods Mol. Biol., 669, 43-55, 2010. 12. Carlos Tassa, Jay L. Duffner, Timothy A. Lewis, Ralph Weissleder, Stuart L. Schreiber, Angela N. Koehler, Stanley Y. Shaw. “Binding affinity and kinetic analysis of targeted small molecule-modified nanoparticles.” Bioconjugate Chemistry, 21, 14-19, 2010. 13. Benjamin Z. Stanton, Lee F. Peng, Nicole Maloof, Kazuo Nakai, Xiang Wang, Jay L. Duffner, Kennedy M. Taveras, Joel M. Hyman, Sam W. Lee, Angela N. Koehler, James K. Chen, Julia L. Fox, Anna Mandinova, Stuart L. Schreiber. “A small molecule that binds Hedgehog and blocks signaling in human cells.” Nature Chemical Biology, 5, 154-156, 2009. This article was featured in the Science & Technology Concentrates section of Chemical and Engineering News, 87, 4, 31, 2009. 14. Yingwei Mao, Xuecai Ge, Christopher L. Frank, Jon Madison, Angela N. Koehler, Mary K. Doud, Carlos Tassa, Erin M. Berry, Tracey L. Petryshen, Takahiro Soda, Travis Biechele, Randall T. Moon, Stephen J. Haggarty, Li- Huei Tsai. “DISC1 regulates neural progenitor proliferation via modulation of GSK3β/β-catenin signaling.” Cell, 136, 1017-1031, 2009. Cover image. 15. Shao-En Ong, Monica Schenone, Adam A. Margolin, Xiaoyu Li, Kathy Do, Mary K. Doud, Denkanikota R. Mani, Letian Kuai, Xiang Wang, John L. Wood, Nicola J. Tolliday, Angela N. Koehler, Lisa A. Marcaurelle, Todd R. Golub, Robert J. Gould, Stuart L. Schreiber, Steve A. Carr. “Identifying the proteins to which small-molecule probes and drugs bind in cells.” Proc. Natl. Acad. Sci. USA, 106, 4617-4622, 2009. 16. Angela N. Koehler.* “Microarrays in chemical biology.” Chapter, Wiley Encyclopedia of Chemical Biology, Tadhg Begley, Editor, ISBN: 978-0-471-75477-0, 2009. 17. Arturo J. Vegas, Jason H. Fuller, Angela N. Koehler.* “Small-molecule microarrays as tools in ligand discovery.” Chem. Soc. Rev., 37, 1385-1394, 2008. 18. Thomas J. F. Nieland, Jared T. Shaw, Firoz A. Jaipuri, Jay. L. Duffner, Angela N. Koehler, Sotirios Banakos, Vassilis I. Zannis, Tom Kirchhausen, Monty Krieger. “Identification of the molecular target for small molecule inhibitors of HDL receptor SR-BI activity.” Biochemistry, 47, 460-472, 2008. 19. Katja Schmitz, Stephen J. Haggarty, Olivia M. McPherson, Jon Clardy, Angela N. Koehler.* “Detecting binding interactions using microarrays of natural product extracts.” J. Am. Chem. Soc., 129, 11346-11347, 2007. 20. Arturo J. Vegas, James E. Bradner, Weiping Tang, Olivia M. McPherson, Edward F. Greenberg, Angela N. Koehler, Stuart L. Schreiber. “Fluorous-based small-molecule microarrays for the discovery of histone deacetylase inhibitors.” Angew. Chem. Int. Ed. 46, 7960-7964, 2007. This article was featured in the Science & Technology Concentrates section of Chemical and Engineering News, 85, 40, 30, 2007. 21. Thomas J. F. Nieland, Jared T. Shaw, Firoz A. Jaipuri, Zoltan Maliga, Jay L. Duffner, Angela N. Koehler, Monty Krieger. “Influence of clinical and experimental HDL-cholesterol elevating drugs on the activity of the HDL receptor SR-BI.” J. Lipid Res., 48, 1832-1845, 2007. 22. Hua Miao, John A. Tallarico, Hiroyuki Hayakawa, Karl Münger, Jay L. Duffner, Angela N. Koehler, Stuart L. Schreiber, Timothy A. Lewis. “Ring-opening and ring-closing reactions of a shikimic acid-derived substrate leading to diverse small molecules.” J. Comb. Chem. 9, 245-253, 2007. 23. Jay L. Duffner, Paul A. Clemons, Angela N. Koehler.* “A pipeline for ligand discovery using small-molecule microarrays.” Curr. Opin. Chem. Biol. 11, 74-82, 2007. 24. James E. Bradner, Olivia M. McPherson, Angela N. Koehler.* “A method for the covalent capture and screening of diverse small molecules in a microarray format.” Nature Protocols, 1, 2344-2352, 2006. 25. Nicola Tolliday, Paul A. Clemons, Paul Ferraiolo, Angela N. Koehler, Timothy A. Lewis, Xiaohua Li, Stuart L. Schreiber, Daniela S. Gerhard, Scott Eliasof. “Small molecules, big players: The National Cancer Institute’s Initiative for Chemical Genetics.” Cancer Res. 66, 1-8, 2006. Cover image. 26. James E. Bradner, Olivia M. McPherson, Ralph Mazitschek, David Barnes-Seeman, John P. Shen, Jasmeet Dhaliwal, Jay L. Duffner, Kristen E. Stevenson, Seung Bum Park, Donna S. Neuberg, Paul Nghiem, Stuart L. Schreiber, Angela N. Koehler.* “A robust small-molecule microarray platform for screening cell lysates.” Chem. Biol. 13, 493-504, 2006. This article was featured in the Research Highlights section of Nature Biotechnology, 24, 799, 2006.
Graduate and Undergraduate Studies
27. Angela N. Koehler, Alykhan F. Shamji, Stuart L. Schreiber. “Discovery of an inhibitor of a transcription factor using small molecule microarrays and diversity-oriented synthesis.” J. Am. Chem. Soc. 125, 8420-8421, 2003. 28. David Barnes-Seeman, Seung Bum Park, Angela N. Koehler, Stuart L. Schreiber. “Expanding the functional group compatibility of small-molecule microarrays: discovery of novel calmodulin ligands.” Angew. Chem. Int. Ed. 42, 2376-2379, 2003. Cover image. 29. Paul A. Clemons, Angela N. Koehler, Bridget K. Wagner, Timothy G. Sprigings, David R. Spring, Randall W. King, Stuart L. Schreiber, Michael A. Foley. “A one bead, one stock solution approach to chemical genetics: Part 2.” Chem. Biol. 8, 1183-1195, 2001. 30. Gavin MacBeath, Angela N. Koehler, Stuart L. Schreiber. “Printing small molecules onto microarrays and detecting protein-ligand interactions en masse.” J. Am. Chem. Soc. 121, 7697-7698, 1999. 31. Arthur Glasfeld, Angela N. Koehler, Maria A. Schumacher, Richard G. Brennan. “The role of lysine 55 in determining the specificity of the purine repressor for its operators through minor groove interactions.” J. Mol. Biol. 291, 347-361, 1999.
Patent Applications
1. “Methods for modulating NF-κB.” A. N. Koehler. Harvard University. (61/110,728). 2. “Selective histone deacetylase inhibitors.” A. N. Koehler, J. E. Bradner, J. H. Fuller, N. West. Harvard University. (61/105,589). 3. “Inhibition of Aurora A kinase with spirooxindoles for treatment of cancer, inflammatory, and autoimmune diseases.” K. Münger, A. N. Koehler, H. Hayakawa, C. S. Neumann, M. M. C. Lo, T. A. Lewis, S. L. Schreiber. P.M. Howley. Harvard University. (60/938,362). 4. “Shikimic acid-derived compounds for inhibition and detection of Aurora A-associated tumors.” K. Münger, H. Hayakawa, P. M. Howley, A. N. Koehler, T. A. Lewis, H. Miao, S. L. Schreiber, J. A. Tallarico. Harvard University. (60/841,035) 5. Therapeutic methods using WRN binding molecules.” B. A. Gilchrest, Mark S. Eller, A. N. Koehler, O. M. McPherson, C. S. Neumann, T. A. Lewis. Boston University. (60/823,876). Exclusively licensed. 6. “Small molecule printing.” D. Barnes-Seeman, J. E. Bradner, R. Mazitschek, S. L. Schreiber, A. N. Koehler. Harvard University. (60/755,946). Exclusively licensed. 7. "1,3-Dioxane small molecules that bind with high affinity to human papillomavirus type 16 E2 protein." P. Meneses, A. N. Koehler, J. C. Wong, S. L. Schreiber, P. M. Howley. Harvard Medical School. US 2005/0123902. 8. "Printing small molecule microarrays and detecting protein-ligand interactions en masse." S. L. Schreiber, G. MacBeath, A. N. Koehler, P. J. Hergenrother, K. M. Depew. Harvard University. US Patent 6,824,987. Nonexclusively licensed to three companies.
Seminars
1. AACR Special Conference on Chemical Systems Biology: Assembling and Interrogating Computational Models of the Cancer Cell by Chemical Perturbations, Boston, MA. 6/30/12. 2. Cold Spring Harbor Laboratory, Transcription and Cancer Banbury Meeting, Cold Spring Harbor, NY. 4/10/12 3. Baylor College of Medicine, Department of Pharmacology Seminar, Houston, TX. 2/27/12 4. Harvard Medical School, Chemical Biology Boot Camp Series, Cambridge, MA. 1/19/12 5. Harvard University, Chemical Biology Practitioner Series, Cambridge, MA. 10/13/11 6. National Academy of Sciences, Indo-American Kavli Frontiers of Science Symposium, Irvine, CA. 4/21/11 7. GlaxoSmithKline, Adventures in Chemical Biology Seminar Series, Waltham, MA. 12/3/10 8. Georgetown University Medical Center, Lombardi Comprehensive Cancer Center, Tumor Biology Visiting Professorship Seminar, Washington, DC. 10/22/10 9. Gordon Research Conference Seminar: High-Throughput Chemistry & Chemical Biology, Les Diablerets, Switzerland. 6/22/10 10. St. Lawrence University, Merck/AAAS Seminar in Chemical Biology, Canton, NY. 04/22/10 11. University of Colorado at Boulder, Organic Chemistry Division Seminar, Boulder, CO. 11/16/09 12. Steacie Institute for Molecular Sciences, Institute Seminar, National Research Council of Canada, Ottawa, ON. 10/15/09 13. Midsummer Nights’ Science at the Broad Institute Series, Cambridge, MA. 7/22/09 14. The Museum of Science, Inspiring Minds: Meet Women in Science Program, Boston, MA. 4/30/09 15. Huntsman Cancer Institute, University of Utah, Stem Cell Symposium on Nuclear Control of Cell Growth and Differentiation, Salt Lake City, UT. 2/23/09 16. Stanford University, Joint Physical Chemistry and Pathology Seminar, Stanford, CA. 2/17/09 17. Princeton University, Department of Chemistry Seminar, Princeton, NJ. 12/2/08 18. MIT, Chemistry-Biology Interface Training Program, Cambridge, MA. 11/24/08 19. Harvard Business School, 9th Annual HBS Health Industry Alumni Seminar. Boston, MA. 11/8/08 20. Schering-Plough, Lead Discovery Group Seminar, Kenilworth, NJ. 4/1/08 21. The Museum of Science, The 13th Annual Symposium on Biotechnology Education, Boston, MA. 3/31/08 22. Massachusetts General Hospital, Center for Cancer Research Seminar, Charlestown, MA. 10/22/07 23. National Research Council of Canada, Genomics and Health Initiative Seminar, Halifax, NS. 5/24/07 24. Harvard University, The 4th Annual National Symposium on the Advancement of Women in Science, Panel Discussion on Drug Discovery, Cambridge, MA. 4/14/07 25. The Salk Institute, Salk/Nature/Ipsen Foundation Symposium on Biological Complexity: Diseases of Transcription, Short Talk, La Jolla, CA. 1/13/07 26. University of Wisconsin at Madison, Genome Center Seminar, Madison, WI. 10/19/06 27. University of Michigan, Life Sciences Institute, Chemical Genomics Colloquium, Ann Arbor, MI. 9/15/06 28. Memorial Sloan-Kettering Cancer Center, Molecular Pharmacology Seminar, New York, NY. 2/20/06 29. University of California, Los Angeles, Department of Chemistry and Biochemistry Seminar, Los Angeles, CA. 1/30/06 30. University of California, Berkeley, Organic Chemistry Seminar, Berkeley, CA. 1/27/06 31. Yale University, Organic Chemistry Seminar, New Haven, CT. 1/9/06 32. Massachusetts General Hospital, Cutaneous Biology Seminar, Charlestown, MA. 3/31/03 33. National Cancer Institute, ICMIC/SAIRP Cancer Imaging Meeting, Herndon, VA. 7/24/02 34. Bauer Center for Genomics, Harvard University, Research Seminar, Cambridge, MA. 4/17/02