Angela N. Koehler
Broad Institute of MIT and Harvard
Chemical Biology Program
Office 3029
7 Cambridge Center
Cambridge, MA 02142
Office: 617-714-7364
Cell: 617-501-1834
Fax: 617-714-8943
Email: [email protected]
Website: www.broadinstitute.org/node/2445
Education
Ph.D. Chemistry, Harvard University, 2003
B.A. Biochemistry and Molecular Biology, Reed College, 1997
Professional Positions
Assistant Professor, Department of Biological Engineering, Massachusetts Institute of Technology
Intramural Faculty, David H. Koch Institute for Integrative Cancer Research at MIT
Associate Member, Broad Institute of MIT and Harvard
2014-present
Director, Transcriptional Chemical Biology, Center for Science of Therapeutics, Broad Institute
2013-present
Investigator, Chemical Biology Program, Broad Institute
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Project & Center Manager, Broad NCI Cancer Target Discovery and Development (CTD ) Center
2009-2013
2010-2012
Institute Fellow, Chemical Biology Program, Broad Institute
Director, Ligand Discovery, NCI Initiative for Chemical Genetics (ICG) at Harvard
2003-2009
2003-2009
Research Experience
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
Laboratory of Professor Barbara Imperiali
Project: Biochemical reconstitution of the oligosaccharyltransferase (OST) complex
1997-1998
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 34 trainees, including postdoctoral fellows, visiting students, undergraduates, etc.
Massachusetts Institute of Technology and Broad Institute
Instructor, Biochemical Sciences Research for Undergraduates (BS91r)
Harvard University
Associated Faculty, Experimental Research in the Life Sciences (LS100r)
Harvard University
2003-present
2004-2006, 2010-2011
2009
Associated Faculty, Experimental Molecular and Cellular Biology (MCB100)
Harvard University
2004-2006
Teaching Fellow, Chemical Biology (Chem 170)
Harvard University, Professor David R. Liu
1999, 2000
Teaching Fellow, The Organic Chemistry of Life (Chem 27)
Harvard University, Professor Stuart L. Schreiber
1999
Teaching Assistant, Techniques of Experimental Chemistry
California Institute of Technology, Dr. Jane Raymond
1997-1998
Teaching Assistant, General Chemistry and Biochemical Methods Laboratory Sections
Reed College, Professors Ronald W. McClard and Arthur Glasfeld
1995-1997
Professional Service
Standing Member, NIH Drug Discovery and Molecular Pharmacology (DMP) Study Section
Scientific Review Panel, Florida Translational Research Program, Sanford-Burnham Institute
Broad@10 Leadership and Connectivity Committee, Broad Institute
Lawrence H. Summers Fellowship Selection Committee
Ad Hoc Member, NIH Drug Discovery and Molecular Pharmacology (DMP) Study Section
Science of Therapeutics (SofT) Organizing Committee (Chair 2013- ), Broad Institute
Ad Hoc Member, NIH Synthetic and Biological Chemistry B (SBCB) Study Section
Principal Advisor, STEMid
Chemical Biology Program Leadership Committee, Broad Institute
Advisory Panel, NRC Canada, Genomics and Health Initiative, BioChips Project
Broad Institute Educational Outreach Program Admissions Panel and Research Mentor
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Intel National Science Talent Search Mentor (Megan Blewett, 7 -place out of 1,700)
High-Throughput Screening Review Board, Broad Institute
Chembank Steering Committee, NCI Initiative for Chemical Genetics
Technology Platform Committee, Broad Institute
2013-2019
2013-2015
2013-2014
2012
2012
2011-present
2011
2011-2013
2010-2013
2008-2011
2007-2012
2006-2007
2005-2012
2005-2006
2004-2006
Honors and Awards
Merkin Institute Fellow at the Broad Institute of MIT and Harvard
Genome Technology Young Investigator
Kavli Frontiers of Science Scholar, US National Academy of Sciences
Indo-US Frontiers of Science Exchange Award
Eli Lilly Predoctoral Fellowship in Organic Chemistry, Harvard University
MIT 50K Entrepreneur Competition, Finalist
Excellence in Scholarship Award, Reed College
William and Jane Einzig Memorial Scholarship, Reed College
ESCO Undergraduate Scholarship, Reed College
2013-2014
2012-2013
2011
2011
2001-2002
2001
1995-1997
1993-1997
1993-1997
Publications
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Marius S. Pop, Nicolas Stransky, Colin W. Garvie, Jean-Philippe Theurillat, Timothy A. Lewis, Elizabeth K.
Culyba, Fallon Lin, Doug S. Daniels, Raymond Pagliarini, Lucienne Ronco, Angela N. Koehler, Levi. A.
Garraway. “A small molecule that binds and inhibits ETV1 transcription factor oncoprotein.” In revision, October
2013.
Yikai Wang, Jean-Yves Wach, Patrick Sheehan, Cheng Zhong, Chenyang Zhan, Richard Harris, Steven C.
Almo, Joshua Bishop, Stephen J. Haggarty, Alexander Ramek, Kayla Berry, Conor O’Herin, Angela N. Koehler,
Alvin W. Hung, Damian W. Young. “Fragment-based approach using diversity-oriented synthesis yields a GSK3β
inhibitor.” Submitted October 2013.
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.
Melissa M. Kemp, Michel Weïwer, Angela N. Koehler.* “Unbiased binding assays for discovering smallmolecule probes and drugs.” Bioorg. Med. Chem., 20, 1979-1989, 2012.
Dominick E. Casalena, Dina Wassaf, Angela N. Koehler.* “Ligand discovery using small-molecule microarrays.”
Chapter, Methods Mol. Biol., 803, 249-263, 2012.
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 hydroxypyrimidine scaffold.” Bioorg. Med. Chem. Lett., 21, 4164-4169, 2011.
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.
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Myung-Soo Kang, Eun Kyung Lee, Vishal Soni, Timothy A. Lewis, Angela N. Koehler, Viswanathan
Srinivasana, Elliott Kieff. ‘Roscovitine inhibits EBNA1 Serine 393 phosphorylation, nuclear localization,
transcription, and episome maintenance.” J. Virol. 85, 2859-2868, 2011.
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.
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.
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.
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.
Arturo J. Vegas, Angela N. Koehler.* “Detecting protein-small molecule interactions using fluorous smallmolecule microarrays.” Methods Mol. Biol., 669, 43-55, 2010.
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.
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.
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, LiHuei Tsai. “DISC1 regulates neural progenitor proliferation via modulation of GSK3β/β-catenin signaling.” Cell,
136, 1017-1031, 2009. Cover image.
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.
Angela N. Koehler.* “Microarrays in chemical biology.” Chapter, Wiley Encyclopedia of Chemical Biology,
Tadhg Begley, Editor, ISBN: 978-0-471-75477-0, 2009.
Arturo J. Vegas, Jason H. Fuller, Angela N. Koehler.* “Small-molecule microarrays as tools in ligand discovery.”
Chem. Soc. Rev., 37, 1385-1394, 2008.
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.
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.
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.
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.
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.
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.
26. 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.
27. 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.
28. 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
29. 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.
30. 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.
31. 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.
32. 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.
33. 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
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“Methods for modulating NF-κB.” A. N. Koehler. Harvard University. (61/110,728).
“Selective histone deacetylase inhibitors.” A. N. Koehler, J. E. Bradner, J. H. Fuller, N. West. Harvard University.
(61/105,589).
“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).
“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)
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.
“Small molecule printing.” D. Barnes-Seeman, J. E. Bradner, R. Mazitschek, S. L. Schreiber, A. N. Koehler.
Harvard University. (60/755,946). Exclusively licensed.
"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.
"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
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Gordon Conference Research Seminar: Bioorganic Chemistry, Proctor Academy, Andover, NH. 6/9/13
Yale Chemical Biology Symposium, New Haven, CT. 5/10/13
AACR National Meeting, New Paradigms in Molecular Pharmacology Session, Washington, DC. 4/6/13
National Cancer Institute, CCR Molecular Discovery Program Seminar Series, Frederick, MD. 4/4/13
Massachusetts Institute of Technology, Department of Biological Engineering Seminar, Cambridge, MA. 3/21/13
Institute for Neurodegenerative Diseases, University of California, San Francisco, CA. 2/28/13
RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA. 12/17/12
Harvard University, Chemical Biology Practitioner Series, Cambridge, MA. 10/23/12
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AACR Special Conference on Chemical Systems Biology: Assembling and Interrogating Computational Models
of the Cancer Cell by Chemical Perturbations, Boston, MA. 6/30/12.
Cold Spring Harbor Laboratory, Transcription and Cancer Banbury Meeting, Cold Spring Harbor, NY. 4/10/12
Baylor College of Medicine, Department of Pharmacology Seminar, Houston, TX. 2/27/12
Harvard Medical School Chemical Biology Boot Camp, Cambridge, MA. 1/19/12
Harvard University, Chemical Biology Practitioner Series, Cambridge, MA. 10/13/11
National Academy of Sciences, Indo-American Kavli Frontiers of Science Symposium, Irvine, CA. 4/21/11
GlaxoSmithKline, Adventures in Chemical Biology Seminar Series, Waltham, MA. 12/3/10
Georgetown University Medical Center, Lombardi Comprehensive Cancer Center, Tumor Biology Visiting
Professorship Seminar, Washington, DC. 10/22/10
Gordon Research Conference Seminar: High-Throughput Chemistry & Chemical Biology, Les Diablerets,
Switzerland. 6/22/10
St. Lawrence University, Merck/AAAS Seminar in Chemical Biology, Canton, NY. 04/22/10
University of Colorado at Boulder, Organic Chemistry Division Seminar, Boulder, CO. 11/16/09
Steacie Institute for Molecular Sciences, Institute Seminar, National Research Council of Canada, Ottawa, ON.
10/15/09
Midsummer Nights’ Science at the Broad Institute Series, Cambridge, MA. 7/22/09
The Museum of Science, Inspiring Minds: Meet Women in Science Program, Boston, MA. 4/30/09
Huntsman Cancer Institute, University of Utah, Stem Cell Symposium on Nuclear Control of Cell Growth and
Differentiation, Salt Lake City, UT. 2/23/09
Stanford University, Joint Seminar for the Departments of Chemistry and Pathology, Stanford, CA. 2/17/09
Princeton University, Department of Chemistry Seminar, Princeton, NJ. 12/2/08
Massachusetts Institute of Technology, Chemistry-Biology Interface Training Program, Cambridge, MA. 11/24/08
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Harvard Business School, 9 Annual HBS Health Industry Alumni Seminar. Boston, MA. 11/8/08
Schering-Plough, Lead Discovery Group Seminar, Kenilworth, NJ. 4/1/08
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The Museum of Science, The 13 Annual Symposium on Biotechnology Education, Boston, MA. 3/31/08
Massachusetts General Hospital, Center for Cancer Research Seminar, Charlestown, MA. 10/22/07
National Research Council of Canada, Genomics and Health Initiative Seminar, Halifax, NS. 5/24/07
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Harvard University, The 4 Annual National Symposium on the Advancement of Women in Science, Panel
Discussion on Drug Discovery, Cambridge, MA. 4/14/07
The Salk Institute, Salk/Nature/Ipsen Foundation Symposium on Biological Complexity: Diseases of
Transcription, Short Talk, La Jolla, CA. 1/13/07
University of Wisconsin at Madison, Genome Center Seminar, Madison, WI. 10/19/06
University of Michigan, Life Sciences Institute, Chemical Genomics Colloquium, Ann Arbor, MI. 9/15/06
Memorial Sloan-Kettering Cancer Center, Molecular Pharmacology Seminar, New York, NY. 2/20/06
University of California, Los Angeles, Department of Chemistry and Biochemistry Seminar, Los Angeles, CA.
1/30/06
University of California, Berkeley, Organic Chemistry Seminar, Berkeley, CA. 1/27/06
Yale University, Organic Chemistry Seminar, New Haven, CT. 1/9/06
Massachusetts General Hospital, Cutaneous Biology Seminar, Charlestown, MA. 3/31/03
National Cancer Institute, ICMIC/SAIRP Cancer Imaging Meeting, Herndon, VA. 7/24/02
Bauer Center for Genomics, Harvard University, Genomics Research Seminar, Cambridge, MA. 4/17/02
Active Federal Funding
1R01 CA160860-01 (Koehler, A.N.)
07/01/12-04/30/16
NIH, NCI
Developing Direct Small-Molecule Probes of Myc-Dependent Transcription
The transcription factor c-Myc is involved in regulating expression of 15% of all genes including several that control cell
cycle, growth, proliferation, and differentiation. Deregulation of c-Myc occurs through several mechanisms and is one
of the most common oncogenic events in human malignancies. c-Myc, like many oncogenic transcription factors, is a
promising yet untested target for cancer therapy due to the lack of potent small molecules that directly modulate Myc
function in cells. The overall aim of this project is to develop direct small-molecule probes of c-Myc that will be used to
study Myc-dependent transcription in normal and neoplastic cells with the goal of clarifying the potential of c-Myc as a
therapeutic target.
Role: PI
2R01 HD032067-14 (Matzuk, M.M.)
NIH, NICHD
Bone Morphogenic Protein Signaling Pathways in Uterine Biology
08/17/94-06/30/15
The transforming growth factor 2 (TGF2) superfamily is the largest family of secreted proteins in mammals, and TGF2
signaling pathways have been implicated in a diversity of developmental and pathophysiological processes including
preeclampsia. The objectives of this project are to mechanistically define the unique and redundant roles of the bone
morphogenetic protein (BMP) type 1 and type 2 receptors during implantation and post-implantation and to identify
new drugs for inhibiting or mimicking the functions of BMPs, activins, and myostatin for treatments of clinically
important reproductive and non-reproductive diseases.
Role: Project Director, PI of subaward from Baylor College of Medicine