Edward J. Brignole, Ph.D.

Massachusetts Institute of Technology • Building 68-695
77 Massachusetts Avenue • Cambridge, MA 02139
617-715-4891 (lab) • www.mit.edu/~brignole • brignole@mit.edu

Understanding the assembly and regulation of macromolecular machines through studies of their dynamic structures, primarily using 3D electron microscopy

Postdoctoral Fellow with Catherine Drennan Sep 2010 - present
Howard Hughes Medical Institute and Department of Chemistry,
Massachusetts Institute of Technology, Cambridge,MA
1) Using electron microscopy to investigate the oligomeric organization of ribonucleotide reductase
2) Determining the structure of oxalate oxidoreductase by X‑ray crystallography

Postdoctoral Fellow in the laboratory of Francisco Asturias Feb 2006 - Sep 2010
Department of Cell Biology, The Scripps Research Institute, La Jolla, CA
Investigated the conformational flexibility of metazoan fatty acid synthase and the assembly of transcription factor IIH using single-particle macromolecular electron microscopy

Postdoctoral Fellow in laboratory of Wade GibsonApr - Dec 2005
Department of Pharmacology and Molecular Sciences,
Johns Hopkins University School of Medicine,Baltimore, MD
Continuation of thesis work on role of herpesvirus protease precursor in capsid assembly

Ph.D.,Biochemistry, cellular and Molecular Biology Graduate Training Program 2005
Johns Hopkins University School of Medicine, Baltimore, MD
Thesis: "Expression and purification of the human cytomegalovirus protease precursor: initial characterizations of its physical and enzymatic properties: Thesis advisor: Wade Gibson

B.S., Biochemisty, Cum Laude, Departmental Honors 1997
Lebanon Valley College, Annville, PA
Thesis: "Chemometric analysis of 1) powdered buttermilk using Raman spectroscopy and 2) raw whole cocoa beans using Aroma Scan" (Collaborations with McCormick & Co, Inc. and Hershey Foods Corp.) Thesis advisor: Donald Dahlberg

Research Rotation with George Rose, John Hopkins U. School MedicineSpring 1998
Research Rotation with Gary S. Hayward, Johns Hopkins U. School Medicine Fall 1997
Research Intern, Lebanon Valley College & Hershey Foods Corp.1994 - 1997

NIH National Research Service Award for Postdoctoral Fellows (F32-DK080622)Sep 2007 - Sep 2010
"Mammalian fatty acid synthase: conformational changes associated with catalysis

Supervised undergraduate research:
Samuel Thompson (MIT), currently a senior Summer 2011 - present
Brian Castellano (HHMI EXROP), currently a senior at San Jose State U. Summer 2012
Ben Bell (MIT), currently a junior Spring 2012
Stephen McCartney (JHU) currently MD/PhD at Washington U. Fall 2000 - 2004

Instructor, Taking snapshots of protein complexes in action Spring 2011
Co-developed and taught a seminars course for advanced undergraduates on macromolecular electron microscopy and small-angle X-ray scattering Massachusetts Institute of Technology

Teaching assistant, Graduate cell biology Spring 2009 The Scripps Research Institute (Instructor: Larry Gerace)

Technical Services Committee, The Scripps Reasearch InstituteJuly 2007 - June 2010
Maintain electron microscopes and ancillary equipment

Safety Officer for Asturias Laboratory, The Scripps Research InstituteJuly 2007 - June 2010
Ensure lab compliance with environmental health and safety

Council of Scientific Editors, The Scripps Research InstituteNov 2008 - Aug 2010
Review colleagues' manuscripts and grant applications

Minnihan EC, Brignole* EJ, Ando* N, Olshansky* L, Chittuluru J, Asturias FJ, Drennan CL,Nocera DG, Stubbe J. Generation of a stable aminotyrosyl radical-induced α2β2 complex of E. coli class Ia RNR. PNAS. Accepted for publication.

Zimanyi CM, Ando N, Brignole EJ, Asturias FJ, Stubbe J, Drennan CL. Tangled up in knots - structures of inactivated forms of E. cloi ribonucleotide reductase. Structure 2012 Aug 8;20(8):1374-83

Aye Y, Brignole EJ, Long MJC, Chittuluru J, Drennan CL, Asturias FJ, Stubbe J. Clofarabine targets the large subunit of human ribonucleotide reductase in vivo by assembly into persistent hexamers. Chem Biol. 2012 Jul 27;19(7):799-805.

Brignole* EJ,Ando* N, Zimanyi CM, Drennan CL. The prototypic class Ia ribonucleotide reductase from Escherichia coli: still surprising after all these years. Biochem Soc Trans. 2012 Jun;40(3):523-30.

Gibbons BJ, Brignole EJ, Azubel M, Murakami K, Voss NR, Bushnell DA, Asturias FJ, Kornberg RD. Subunit architecture of general transcription factor TFIIH.PNAS 2012 Feb;109(6):1949-54.

Brignole* EJ, Ando* N, Zimanyi CM, Funk MA, Yokoyama K, Asturias FJ, Stubbe J, Drennan CL. structural interconversions modulate activity of E. coli ribonucleotide reductase PNAS 2011 Dec; 108(52):21046-21051 (* Co-first authors, order changed for emphasis)

Fernandes SM, Brignole EJ, Taori K, Gibson W. Cytomegalovirus capsid protease: biological substrates are cleaved more efficiently by full-length enzyme (pUL80a) than by the catalytic domain (assemblin). J Virol. 2011 Apr;85(7):3526-34.

Brignole EJ, Asturias F. Single-particle electron microscopy of animal fatty acid synthase: describing macromolecular rearrangements that enable catalysis. Methods Enzymol. 2010; 483:179-202.

Voss NR, Cheng A, Lau P-W, Mulder A, Lander GC, Brignole EJ, Fellmann D, Irving C, Jacovetty EL, Leung A, Pulokas J, Quispe JD, Winkler H, Yoshioka C, Carragher B, Potter CS. A toolbox for ab initio 3 D reconstructions in single-particle electron microscopy. J Struct Biol. 2010 Mar; 169(3):389-398.

Brignole EJ, Smith S, Asturias FJ. Conformational flexibility of metazoan fatty acid synthase enables catalysis. Nat Struct Mol Biol. 2009 Feb; 16(2):190-7. Featured on cover.

Brignole EJ, Gibson W. Enzymatic activities of human cytomegalovirus maturational protease assemblin and its precursor (pPR, pUL80a) are comparable: maximal activity of pPR requires self-interaction through its scaffolding domain. J Virol. 2007 Apr; 81(8):4091-4103.

Loveland AN, Nguyen NL, Brignole EJ, Gibson W. Amino-conserved domain of human cytomegalovirus UL80a proteins is required for key interactions during early stages of capsid formation and virus production. J Virol. 2007 Jan; 81(2):620-8.

Loveland AN, Chan CK, Brignole EJ, Gibson W. Cleavage of human cytomegalovirus protease (pUL80a) at internal and cryptic sites is not essential but enhances infectivity. J Virol. 2005 Oct; 79(20):12961-8.

McCartney SA, Brignole EJ, Kolegraff KN, Loveland AN, Ussin LM, Gibson W. Chemical rescue of I-site cleavage in living cells and in vitro: evidence for active site difference between cytomegalovirus protease, assemblin, and its precursor (pUL80a). J Biol Chem. 2005 Sep; 280(39):33206-12.

Casaday RJ, Bailey JR, Kalb SR, Brignole EJ, Loveland AN, Cotter RJ, Gibson W. Assembly protein precursor (UL80.5 homolog) of Simian Cytomegalovirus is phosphorylated at a glycogen synthase kinase 3 site and its downstream "priming" site: phosphorylation affects interactions of protein with itself and with major capsid proteins. J Virol. 2004 Dec; 78(24):13501-11.

Chan CK, Brignole EJ, Gibson W. Cytomegalovirus assemblin (pUL80a): cleavage at internal site not essential for virus growth; proteinase absent from virions. J Virol. 2002 Sep; 76(17):8667-74.

Ahn JH, Brignole EJ 3rd, Hayward GS. Disruption of PML subnuclear domains by the acidic IE1 protein of human cytomegalovirus is mediated through interaction with PML and may modulate a RING finger-dependent cryptic transactivator function of PML. Mol Cell Biol. 1998 Aug; 18(8):4899-913.

Ed Brignole. ON target. News In Brief Article for Modern Drug Discovery. June 2002. American Chemical Society Publications

Ed Brignole. Viral RNA: takes your breath away? News In Brief Article for Modern Drug Discovery. Mar 2002. American Chemical Society Publications

Ed Brignole. Microfluidic microarrays. News In Brief Article for Modern Drug Discovery. Jan 2002. American Chemical Society Publications

Ed Brignole. Tailor-made anticancer vaccines. News In Brief Article for Modern Drug Discovery. Oct 2001. American Chemical Society Publications

Ed Brignole. Microscopically measuring Kd. News In Brief Article for Modern Drug Discovery. Sep 2001. American Chemical Society Publications

Ed Brignole. Resisting resistance. News In Brief Article for Modern Drug Discovery. Sep 2001. American Chemical Society Publications

Ed Brignole. Just a spoonful of sugar. News In Brief Article for Modern Drug Discovery. May 2001. American Chemical Society Publications

Ed Brignole and Julie McDowell. Amino acid racemization. Feature Article for Today's Chemist at Work. Feb 2001. American Chemical Society Publications

Ed Brignole. Laser capture microdissection. Toolbox Article for Modern Drug Discovery. Nov/Dec 2000. American Chemical Society Publications

Ed Brignole. Do you want vaccine with that? News In Brief Article for Modern Drug Discovery. Oct 2000. American Chemical Society Publications

Ed Brignole. Breakthrough treatment for bone cancer patients. News In Brief Article for Modern Drug Discovery. July/Aug 2000. American Chemical Society Publications

Electron microscopy snapshots of ribonucleotide reductase. Boston Area DNA Repair & Mutagenesis Seminar, Massachusetts Institute of Technology. Dec 13, 2011.

Electron microscopy snapshots of ribonucleotide reductase. Massachusetts Institute of Technology, Structural Biology Supergroup. Oct 13, 2011.

Electron microscopy snapshots of a nucleotide reducing machine. Massachusetts Institute of Technology, Biophysics Retreat, Sea Crest Resort. Oct 3, 2011.

The catalytic dance of fatty acid synthase: snapshots of a flexible multienzyme machine in action. Children's Hospital Oakland Research Institute, Symposium in recognition of Stuart Smith's retirement. Oct 15, 2010.

A flexible multi-enzyme machine: snapshots of fatty acid synthase in action. Massachusetts Institute of Technology, Biochemistry Division. Feb 10, 2010.

Molecular snapshots of a flexible multi-enzyme machine: fatty acid synthase in action. Case Western Reserve University, Department of Pharmacology. Apr 3, 2009.

Conformational flexibility of metazoan fatty acid synthase enables catalysis. The Scripps Research Institute, Department of Cell Biology Retreat, Paradise Point Resort, selected presenter. Oct 30, 2008.

The metazoan fatty acid synthase requires extensive structural flexibility for catalysis. (3rd place in Chemistry & Structural Biology) The Scripps Research Institute, Annual Symposium. Oct 2, 2008.

Single-particle electron microscopy reveals conformational changes of metazoan fatty acid synthase that enable catalysis. The Scripps Research Institute, Automated Molecular Imaging Forum. Sep 25, 2008.

Functional and structural studies of a self-digesting, self-interacting enzyme: the human cytomegalovirus protease precursor. Villanova University, Department of Biology. June 10, 2004.

Progress in purifying the HCMV precursor protease and evidence that it differs catalytically from assemblin. Philadelphia Herpesvirus Symposium, University of Pennsylvania. June 9, 2004.

Imidazole rescues histidine mutants of cytomegalovirus protease, assemblin (pUL80a), in living cells and in vitro. Abstract W22-7. 22nd Annual Meeting American Society for Virology, University of California, Davis. July 2003.

Internal cleavage of the proteinase is not essential for HCMV replication. Philadelphia Herpesvirus Symposium, University of Pennsylvania. June 5, 2002.

Edward J. Brignole, Nozomi Ando, Christina Stock, Michael Funk, Kenichi Yokoyama, Francisco J. Asturias, JoAnne Stubbe, Catherine Drennan. Structural transitions that accompany activity regulation of E. coli ribonucleotide reductase. Protein Society. Boston, MA. 2011.

Edward J. Brignole, Nozomi Ando, Christina Stock, Michael Funk, Kenichi Yokoyama, Francisco J. Asturias, JoAnne Stubbe, Catherine Drennan.Structural transitions that accompany activity regulation of E. coli ribonucleotide reductase. Gordon Research Conference on Three-Dimensional Electron Microscopy. Colby-Sawyer College. New London, NH. 2011.

Edward J. Brignole, Stuart Smith, Francisco J. Asturias. Conformational flexibility of metazoan fatty acid synthase enables catalysis. Gordon Research Conference on Three-Dimensional Electron Microscopy. Colby-Sawyer College. New London, NH. 2009.

Wade Gibson, Edward J. Brignole, Rebecca J. Casaday, and Steven A. McCartney. Self-interaction, phosphorylation, cleavage: scaffolding features with potential to modulate herpesvirus capsid formation. FASEB Research Conference on Virus Assembly. Vermont Academy, Saxtons River, VT. 2004.

Stephen A. McCartney, Edward J. Brignole, Keli N. Kolegraff, and Wade Gibson. Imidazole rescues histidine mutants of cytomegalovirus protease, assemblin (pUL80a), in living cells and in vitro. Poster 7.11. 28th International Herpesvirus Workshop. University of Wisconsin, Madison, WI. 2003.

Chee-Kai Chan, Edward J. Brignole, and Wade Gibson. Cytomegalovirus assemblin (pUL80a): cleavage at internal site not essential for virus growth; proteinase absent from virions. Abstract 1-10. FASEB Research Conference on Virus Assembly. Vermont Academy, Saxtons River, VT. 2002.

Donald B. Dahlberg, Edward J. Brignole, Trent S. Snider, Scott J. Wenger, Seth M. Lee, Julie A. Vargo. Chemometrics: trying to keep the promise in the real world. Abstract 175. Eastern Analytical Symposium. Garden State Convention Center, Somerset, NJ, 1997.

American Association for the Advancement of Science, member 2008 - present

The Protein Society, member 2011

Union of Concerned Scientists, member 2005 - present

Cycling, National Championship Team Time Trial (collegiate Div. II), John Hopkins U. 2002 & 2003

Soccer, Cross Country, Track & Field (8 Varsity Letters), Lebanon Valley College 1993 - 1997

President, Class of '97, Lebanon Valley College 1993 - 1997

Cellist, Symphony Orchestra, Lebanon Valley College 1993 - 1997