Timothy Whitehead
Associate Professor

Mailbox: 596 UCB
Office: JSCBB E1B32

Education

University of Washington, Seattle, WA
Senior Fellow, Department of Biochemistry, Feb 2009-Aug 2011
Advisor: David Baker, PhD

University of California-Berkeley, Berkeley, CA
PhD in Chemical Engineering, May 2008
Thesis: Engineering proteins to build nanostructures
Thesis advisor: Douglas S. Clark, PhD

Vanderbilt University, Nashville, TN
BE in Chemical Engineering, magna cum laude, May 2001

Awards

  • College of Engineering Nominee, MSU Teacher/Scholar Award, 2017
  • Johansen Crosby Endowed Chair, CHEMS MSU, 2017
  • Young Scientist Keynote, PEGS Meeting, 2017
  • Fellow, Global Academy MSU, 2017
  • NSF CAREER, 2013
  • NIH T32 pre-doctoral Biotechnology Training Fellowship, 2007

Publications

  • Wrenbeck EE, Bedewitz MA, Klesmith JR, Noshin S, Barry CS, Whitehead TA* (2019) “An automated data-driven pipeline for improving heterologous enzyme expression” ACS Synthetic Biology (in revision)
  • Faber MS, Whitehead TA* (2019) “Data-driven engineering of protein therapeutics”, Current Opinion in Biotechnology in press
  • Medina-Cucurella A^, Zhu Y, Bowen SJ, Bergeron LM, Whitehead TA* (2018) “Pro region engineering of nerve growth factor by deep mutational scanning enables a yeast platform for conformational epitope mapping of anti-NGF monoclonal antibodies”, Biotechnology & Bioengineering, 115:1925-1937 DOI: 10.1002/bit.26706
  • Acquaye-Seedah E, Reczek E, Russell H, Sandman SO&, Collins JH&, Stein CA^, DiVenere A, Whitehead TA, Maynard JA (2018) “Plasmablast derived monoclonal antibody response to pertussis toxin after adult acellular pertussis booster immunization”, Infection & Immunity, 86:6 e00004-18 DOI: 10.1128/IAI.00004-18
  • Medina-Cucurella A^, Whitehead TA* (2018) “Characterizing Protein-Protein Interactions Using Deep Sequencing Coupled to Yeast Surface Display”, Methods in Molecular Biology in Protein Complex Assembly, 101-121
  • Whitehead TA*, (2017) “A peptide mimic of an antibody” Science, in press
  • Whitehead T*, Cutler S, Wheeldon I, (2017) “Plant Metabolic Engineering for Chemicals, Fuels, and Precursors”, Chemical Engineering Progress SBE Supplement (invited)
  • Wrenbeck EE^, Azouz LR&, Whitehead TA* (2017), “Single-mutation fitness landscapes for an enzyme on multiple substrates reveal specificity is globally encoded”, Nature Communications in press
  • Whitehead TA*, Bandi CK, Berger M, Park J, Chundawat S* (2017) “Negatively supercharging cellulases render them lignin-resistant”, ACS Sustainable Chemistry & Engineering in press doi:10.1021/acssuschemeng.7b0120.
    • Cover of ACS Sustainable Chemistry & Engineering
  • Wang X, Stapleton JA^, Klesmith JR^, Hewlett E, Whitehead TA, Maynard J (2017) “Fine epitope mapping of two antibodies neutralizing the Bordetella adenylate cyclase toxin”, Biochemistry 56:1324-1336 doi: 10.1021/acs.biochem.6b01163
  • Klesmith JR^, Bacik JP, Wrenbeck EE^, Michalczyk R, Whitehead TA* (2017) “Trade-offs between enzyme fitness and solubility illuminated by deep mutational scanning”, PNAS 114:2265-2270 doi: 10.1073/pnas.1614437114
  • Wrenbeck EE^, Faber M^, Whitehead TA* (2017) “Deep sequencing methods for protein engineering and design”, Current Opinion in Structural Biology 45:36-44
  • Haarmeyer C^, Smith MD&, Chundawat S, Sammond D, Whitehead TA*, (2017) “Insights into cellulase-lignin non-specific binding revealed by computational redesign of the surface of green fluorescent protein”, Biotechnology & Bioengineering 114:740-750doi:10.1002/bit.26201
  • Kowalsky CA^, Whitehead TA*, (2016) “Determination of binding affinity upon mutation for type I dockerin-cohesin complexes from Clostridium thermocellum and Clostridium cellulolyticum using deep sequencing”, Proteins 84(12): 1914-1928 doi:10.1002/prot.25175
  • Wrenbeck EE^, Klesmith JR^, Adeniran A, Stapleton JA^, Tyo KJ, Whitehead TA*, (2016) “Plasmid-based single-pot saturation mutagenesis”, Nature Methods 13(11): 928-930 doi:10.1038/nmeth.4029
    • Documentation at Nature Protocols Exchange (doi:10.1038/protex.2016.061)
  • Klesmith JR^, Thorwall S&, Whitehead TA* (2016) “Interpreting deep mutational scanning data resulting from plate-based selections”, bioRxiv 087072
  • Stapleton JA^, Kim J, Hamilton JP, Wu M, Irber LC, Maddamsetti R, Briney B, Newton L, Burton DR, Brown CT, Chan C, Buell CR, Whitehead TA* (2016) “Haplotype-phased synthetic long reads from short-read sequencing”, PLoS ONE 11(1):e0147229
  • Khare S*, Whitehead TA* (2015), “Introduction to RosettaCON Special Collection”, PLoS ONE 10(12):e0144326
  • Klesmith JR^, Whitehead TA* (2015), “High-throughput evaluation of synthetic metabolic pathways”, Technology 4(01):9-14
  • Klesmith JR^, Bacik JP, Michalczyk R, Whitehead TA* (2015) “High-resolution sequence function mapping of a levoglucosan utilization pathway in E. coli”, ACS Synthetic Biology 4 (11), 1235-1243 DOI: 10.1021/acssynbio.5b00131
    • Selected for ‘Introducing our Authors’ feature highlight
  • Bacik JP, Klesmith JR^, Whitehead TA, Jarboe LR, Unkefer CJ, Mark BL, Michalczyk R (2015) “Structural insights into bioconversion of the biomass pyrolysis product levoglucosan”, Journal of Biological Chemistry 290 (44), 26638-26648
  • Kowalsky CA^, Faber M^, Nath A, Dann H&, Kelly VW&, Liu L, Shanker P, Wagner EK, Maynard J, Chan C, Whitehead TA* (2015) “Rapid fine conformational epitope mapping using comprehensive mutagenesis and deep sequencing”, Journal of Biological Chemistry 290 (44), 26457-26470 doi:10.1074/jbc.M115.676635
    • Top 5 accessed article for J. Biol. Chem., Oct. 2015
  • Stapleton JA^, Whitehead TA, Nanda V (2015) “Computational redesign of the lipid-facing surface of the outer membrane protein OmpA”, PNAS 112(31):9632-9637
  • Kowalsky CA^, Klesmith JR^, Stapleton JA^, Kelly VW&, Reichkitzer N&, Whitehead TA* (2015) “High-resolution sequence-function mapping of full proteins”, PLoS ONE, 10(3): e0118193. doi:10.1371/journal.pone.0118193
  • Tomek KJ&, Saldarriaga CRC&, Velasquez FPC, Liu T, Hodge DB, Whitehead TA*, (2015) “Removal and upgrading of lignocellulosic fermentation inhibitors by in situ biocatalysis and liquid-liquid extraction”, Biotechnology & Bioengineering, 112(3):627-632. http://onlinelibrary.wiley.com/doi/10.1002/bit.25473/abstract
    • Selected for B&B video highlight
  • Gao D, Haarmeyer C^, Balan V, Whitehead TA, Dale BE, Chundawat SPS (2014) “Lignin triggers irreversible cellulase loss during pretreated lignocellulosic biomass saccarification”, Biotechnology for Biofuels, 7:175
  • Bienick MS&, Young KW&, Klesmith JR^, Detwiler EE^, Tomek KJ&, Whitehead TA*, (2014) “The interrelationship between promoter strength, gene expression, and growth rate”, PLoS ONE, DOI: 10.1371/journal.pone.0109105 http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0109105
  • Whitehead TA*, Baker D, Fleishman SJ* (2013) “Computational design of novel protein binders and experimental affinity maturation”, Methods Enzymology, 523:1-19. doi: 10.1016/B978-0-12-394292-0.00001-1.
  • Whitehead TA+, Chevalier A+, Song Y et al. (2012) “Optimization of affinity, specificity, and function of designed Influenza inhibitors using deep sequencing”, Nature Biotechnology 30(6):543-8. doi: 10.1038/nbt.2214. Cover of Nature Biotechnology; Featured in numerous popular press articles and radio interviews, including NPR.
  • Fleishman SJ, Whitehead TA, Strauch EM et al. (2011) “Community-wide assessment of protein-interface modeling suggests improvements to design methodology”, J Mol Biol 414(2):289
  • Fleishman SJ, Corn JE, Strauch EM, Whitehead TA, Karanicolas J, Baker D (2011) “Hotspot-centric de novo design of protein binders”, J Mol Biol 413(5):1047
  • Fleishman SJ+, Whitehead TA+, Ekiert D+, Dreyfus C, Corn JE, Strauch EM, Wilson IA, Baker D (2011) “Computational design of proteins targeting the conserved stem region of Influenza hemagglutinin”, Science 332(6031):816-21
    • Featured in numerous popular press articles and radio interviews, including NPR.
  • Fleishman SJ, Corn JE, Strauch EM, Whitehead TA, Andre I, Thompson J, Havranek JJ, Das R, Bradley P, Baker D (2010), “Rosetta in CAPRI rounds 13-19” Proteins 78(15):3212
  • Whitehead TA, Bergeron LM, Clark DS (2009), “Tying up the loose ends: circular permutation decreases the proteolytic susceptibility of recombinant proteins” Protein Eng Des Sel 22 (10):607-13
  • Slocik JM, Kim SN, Whitehead TA, Clark DS, Naik RR (2009), “Biotemplated metal nanowires using hyperthermophilic protein filaments”, Small 5 (18):2038-42
  • Bruns N, Pustelny K, Bergeron LM, Whitehead TA, Clark DS (2009), “Mechanical nanosensor based on FRET within a thermosome: damage-reporting polymeric materials”, Angew Chem Int Ed Engl 48 (31):5666-9
  • Whitehead TA, Je E, Clark DS (2009), “Rational shape engineering of the filamentous protein gamma prefoldin through incremental gene truncation”, Biopolymers 91 (6):496-503
  • Bergeron LM, Gomez L, Whitehead TA, Clark DS (2009), “Self-renaturing enzymes: design of an enzyme-chaperone chimera as a new approach to enzyme stabilization”, Biotechnol Bioeng 102 (5):1316-22.
    • Spotlight article in Biotechnol Bioeng
  • Whitehead TA, Meadows AL, Clark DS (2008), “Controlling the self-assembly of a filamentous hyperthermophilic chaperone by an engineered capping protein”, Small 4 (7):956-60
  • Whitehead TA, Boonyaratanakornkit BB, Hoellrigl V, Clark DS (2007), “A filamentous molecular chaperone of the prefoldin family from the deep-sea hyperthermophile Methanocaldococcus jannaschii”, Protein Science 16 (4): 626-634
  • Boonyaratanakornkit BB, Simpson AJ, Whitehead TA, Fraser CM, El-Sayed NMA, Clark DS (2005), “Transcriptional profiling of the hyperthermophilic methanarchaeon Methanococcus jannaschii in response to lethal heat and non-lethal cold shock”, Environmental Microbiology 7 (6): 789-797
  • Laksanalamai P, Whitehead TA, Robb FT (2004), “Minimal protein-folding systems in hyperthermophilic archaea”, Nature Reviews Microbiology 2 (4): 315-324

*Corresponding Author, ^Graduate Student/Postdoc Trainee, &Undergraduate Trainee, +Authors contributed equally

Research Interests

Protein engineering, protein design, biomolecular recognition, renewable energy production, antibody and antibody mimics, antigen design, synthetic biology, biochemical engineering.