Education

Yale University, New Haven
Ph.D. 2012: Biophysical Chemistry

Yale University, New Haven
M.S. 2007: Biophysical Chemistry

University of Michigan, Ann Arbor
B.S. 2005: Chemistry and Biochemistry with Highest Honors

Work Experience

U.S. Environmental Protection Agency, Research Triangle Park, NC
ORISE Postdoctoral Fellow, National Center for Computational Toxicology, Office of Research and Development (May 2014 - Present)

University of Illinois Department of Chemistry, Urbana, IL
Postdoctoral Research Associate (January 2014 - April 2014)
Postdoctoral Fellow — American Heart Association (January 2012 - December 2013)
Visiting Scholar (February 2011 - December 2011)

Yale University Department of Chemistry, New Haven, CT
Graduate Researcher (April 2006 - January 2011)

University of Michigan Department of Chemistry, Ann Arbor, MI
Undergraduate Researcher (May 2003 - August 2005)

Core Expertise

Computational Toxicology

  • Developed and published R package toxboot for uncertainty quantification in ToxCast high-throughput screening assays. Included integration with MySQL and MongoDB databases.
  • Applied uncertainty quantification to numerous models of toxicity including estrogen and androgen predicitive models, cytotoxicity, and zebrafish developmental assays.
  • Processed and analyzed new high-throughput in vitro assay to identify inhibitors of thyroid peroxidase including orthogonal assays to identify and quantify nonspecific inhibition.
  • Developing systems biology model of thyroid hormone system using the Tellurium python package and httk R package to quantify xenobiotic chemical concentrations and impact of inhibition on multiple molecular initiating events to predict thyroid hormone disruption.

Computational Tools

  • Developed and utilized R, python, C, C++, Perl, and Mathematica programs, scripts, and software packages to process and analyze experimental results and develop computational models.
  • Improved the documentation and usability of research outputs using collaboration tools including web interfaces (HTML, CSS, Javascript, Markdown, MediaWiki), version control (git, svn) and Atlassian products (Jira, Bitbucket, Confluence) in research settings.
  • Well versed in use of tools for data visualization and written communication including Adobe Creative Suite (Photoshop, Illustrator, InDesign), Microsoft Office (Word, Excel, Powerpoint, Outlook), LaTeX, and web tools.

Experimental Techniques

  • Analyzed biomolecules using methods such as SDS PAGE, protein activity assays, ultraviolet-visible spectroscopy (UV-Vis), mass spectroscopy, and NMR.
  • Expressed isotopically labeled recombinant proteins using biomolecular tools including site directed mutagenesis, sequencing, transformation, and protein induction.
  • Isolated and purified proteins using manual and automated chromatography systems, such as FPLC Ni-NTA, ion exchange, and size exclusion columns.
  • Conducted experiments to post-translationally modify proteins to augment enzymatic function.
  • Transcribed and purified isotopically labeled RNA for biophysical study.
  • Formulated and conducted NMR experiments to study the structure, dynamics, and biophysical properties of diverse biomolecules including proteins, RNA, lipids, and small molecule ligands and drugs.

Collaborative Research

  • Collaborated with scientists from EPA’s National Center for Computational Toxicology and National Health and Environmental Effects Research Laboratory to improve experimental design of high throughput screening assays and to enhance the methods used to analyze assay results.
  • Worked in a collaborative environment involving partnerships with computational, biochemical, and analytical labs across the University of Illinois to study the proteins and membrane interactions involved in human blood clotting.
  • Initiated and spearheaded the use of electronic record keeping system to facilitate knowledge transfer and collaboration for multiple research groups.

Publications

  1. Nuzzio KM, Watt ED, Boettcher JM, Gajsiewicz JM, Morrissey JH, Rienstra CM. High-Resolution NMR Studies of Human Tissue Factor. PLOS ONE. 2016 Sep 22;11(9):e0163206. doi: 10.1371/journal.pone.0163206
  2. Paul Friedman K*, Watt ED*, Hornung MW, Hedge JM, Judson RS, Crofton KM, et al. Tiered High-Throughput Screening Approach to Identify Thyroperoxidase Inhibitors Within the ToxCast Phase I and II Chemical Libraries. Toxicological Sciences. 2016 May;151(1):160-80. doi: 10.1093/toxsci/kfw034
  3. Courtney JM, Ye Q, Nesbitt AE, Tang M, Tuttle MD, Watt ED, et al. Experimental Protein Structure Verification by Scoring with a Single, Unassigned NMR Spectrum. Structure. 2015 Oct 6;23(10):1958-66. doi: 10.1016/j.str.2015.07.019
  4. Watt ED, Rienstra CM. Recent Advances in Solid-State Nuclear Magnetic Resonance Techniques to Quantify Biomolecular Dynamics. Analytical Chemistry. 2014 Jan 7;86(1):58-64. doi: 10.1021/ac403956k
  5. Watt ED, Rivalta I, Whittier SK, Batista VS, Loria JP. Reengineering Rate-Limiting, Millisecond Enzyme Motions by Introduction of an Unnatural Amino Acid. Biophysical Journal. 2011 Jul;101(2):411-20. doi: 10.1016/j.bpj.2011.05.039
  6. Doucet N, Watt ED, Loria JP. The Flexibility of a Distant Loop Modulates Active Site Motion and Product Release in Ribonuclease A. Biochemistry. 2009 Aug 4;48(30):7160-8. doi: 10.1021/bi900830g
  7. Loria JP, Berlow RB, Watt ED. Characterization of Enzyme Motions by Solution NMR Relaxation Dispersion. Accounts of Chemical Research. 2008 Feb;41(2):214-21. doi: 10.1021/ar700132n
  8. Dethoff EA, Hansen AL, Musselman C, Watt ED, Andricioaei I, Al-Hashimi HM. Characterizing Complex Dynamics in the Transactivation Response Element Apical Loop and Motional Correlations with the Bulge by NMR, Molecular Dynamics, and Mutagenesis. Biophysical Journal. 2008 Oct;95(8):3906-15. doi: 10.1529/biophysj.108.140285
  9. Croke RL, Sallum CO, Watson E, Watt ED, Alexandrescu AT. Hydrogen exchange of monomeric alpha-synuclein shows unfolded structure persists at physiological temperature and is independent of molecular crowding in Escherichia coli. Protein Science. 2008 Aug;17(8):1434-45. doi: 10.1110/ps.033803.107
  10. Watt ED, Shimada H, Kovrigin EL, Loria JP. The mechanism of rate-limiting motions in enzyme function. Proceedings of the National Academy of Sciences. 2007 Jul 17;104(29):11981-6. doi: 10.1073/pnas.0702551104
  11. Zhang Q, Sun X, Watt ED, Al-Hashimi HM. Resolving the motional modes that code for RNA adaptation. Science. 2006 Feb 3;311(5761):653-6. doi: 10.1126/science.1119488

*Both authors contributed equally to this work.

Software

  1. Watt ED. Bootstrap Methods for ToxCast High Throughput Screening Data: toxboot 0.1.1. Zenodo (2016) 10.5281/zenodo.60778

Presentations

  • 2016: American Society for Cellular and Computational Toxicology (ASCCT) 5th Annual Meeting
    Poster: Uncertainty Quantification in High Throughput Screening Models of Endocrine Disruption

  • 2016: Drug Safety Gordon Research Conference
    Poster: Uncertainty Quantification in High Throughput Screening: Applications to Models of Endocrine Disruption, Cytotoxicity, and Zebrafish Development

  • 2016: Drug Safety Gordon Research Seminar
    Talk: Uncertainty Quantification in High Throughput Screening: Applications to Models of Endocrine Disruption, Cytotoxicity, and Zebrafish Development

  • 2016: EPA Computational Toxicology Communities of Practice
    Talk: Analysis of High-throughput screening data from Amplex UltraRed (AUR) Thyroperoxidase (TPO) assays
    Co-presented with Dr. Katie Paul Friedman

  • 2015: EPA Community of Practice for Statistics
    Talk: Game of Uncertainties: A Song of Thyroid Peroxidase and Estrogen Receptor

  • 2015: 54th Society of Toxicology Conference
    Poster: Computational Modeling of Thyroid Hormone Regulated Neurodevelopment for Chemical Prioritization

  • 2013: Gordon Research Conference: Computational Aspects — Biomolecular NMR
    Poster: Tissue factor structure and dynamics studies with solution and solid state NMR

  • 2007: 48th Experimental Nuclear Magnetic Resonance Conference
    Poster: Characterization of Enzyme Dynamics in H48A RNase A

  • 2006: 23rd Eastern Regional Photosynthesis Conference
    Poster: MCCE Modeling of the Proton Exit Channel of the Oxygen Evolving Complex of Photosystem II

  • 2005: 46th Experimental Nuclear Magnetic Resonance Conference
    Poster: Structural Dynamics of Wild Type TAR Using Residual Dipolar Couplings: The Impact of the Loop

Awards

  • 2014-Present: ORISE Postdoctoral Fellowship
  • 2012-2013: American Heart Association Postdoctoral Fellowship
  • 2006: NIH Biophysics Training Grant
  • 2005: NIH Biophysics Training Grant
  • 2004: James B. Angell Scholar
  • 2003: Pittsburgh Plate and Glass Summer Undergraduate Research Fellowship
  • 2002: First Year Chemistry Achievement Awards

Teaching Experience

Yale University Department of Chemistry, New Haven, CT

  • 2010: Physical Chemistry with Applications in the Biological Sciences I
  • 2010: Comprehensive General Chemistry II
  • 2009: Quantitative Foundations of General Chemistry
  • 2008: Physical Chemistry with Applications in the Biological Sciences I
  • 2008: Laboratory for Physical Chemistry II
  • 2007: Laboratory for Physical Chemistry I

University of Michigan Department of Chemistry, Ann Arbor, MI

  • 2004: Introductory Organic Chemistry Lab II TA
  • 2003: Introductory Organic Chemistry Lab I TA
  • 2003: Laboratory Instrument Room Assistant
    Instructed honors organic chemistry lab students on sample preparation and proper use of UV, IR, and NMR spectroscopy equipment