Harrison J. Esterly, PhD

Research

My doctoral research advanced two-dimensional infrared spectroscopy (2D-IR) for biological systems, applying the technique to resolve the toxic oligomeric structure of human islet amyloid polypeptide (hIAPP), a key driver of type 2 diabetes. By stabilizing this transient state and combining 2D-IR, NMR, and molecular dynamics, we obtained the first high-resolution structure of the toxic hIAPP oligomer, revealing molecular surfaces amenable to therapeutic targeting.

In parallel, I characterized the thermal effects of our 100 kHz 2D-IR spectrometer, developing methods to measure and control steady-state sample temperature and identifying an inter-pulse third-order artifact, arising from a hot ground-state, that limits signal-to-noise in dilute solutions. I showed that this artifact can be eliminated under specific polarization conditions, enabling more accurate biophysical measurements.

Previously, I served as the lead researcher in a multinational collaboration between BASF and UNC-Chapel Hill, where I studied the protective properties of tardigrade proteins for industrial applications. As an undergraduate, I investigated the role of oxidative stress in stem-cell differentiation and explored protein-based excipients for biologics, demonstrating their potential to enable dry storage of therapeutics.

More broadly, I am interested in scientific problems where measurement, molecular complexity, and translational potential intersect. That includes protein aggregation, biomolecular condensates, cellular heterogeneity, and emerging tools that connect molecular mechanism to therapeutic or industrial applications.

Publications

  • Symmetry Lost, Function Found: A Spectroscopic Perspective on Excited-State Symmetry Breaking
    McDonnell, R. P.; Faitz, Z. M.; Esterly, H. J.; Cerullo, G.; Gilbert, A. B.; Bianconi, T. ChemPhotoChem 2026, 10, e202500415.
  • A Structural Model of Toxic Amyloid Oligomers Involved in Type-2 Diabetes
    Shivani, T. S.*; Ravula, T.*; LeMasters, B.*; Esterly, H. J.*; Maroli, N.; Rich, K. L.; Fields, C. R.; Stapleton, D. S.; Dicke, S. S.; Warmuth, O.; Keller, M. P.; Attie, A. D.; Kananenka, A. A.; Henzler-Wildman, K.; Rienstra, C. M.; Zanni, M. T. Proc. Natl. Acad. Sci. U.S.A. 2025, 123(5), e2528103123.
    *Authors contributed equally.
  • Mitigation of Thermal Artifacts in 100 kHz Ultrafast 2D IR Spectroscopy
    Esterly, H. J.; Shivani, T. S.; Farrell, K. M.; Zanni, M. T. J. Chem. Phys. 2024, 161(21), 214202.
  • Protection by Desiccation-Tolerance Proteins Probed at the Residue Level
    Crilly, C. J.; Brom, J. A.; Warmuth, O.; Esterly, H. J.; Pielak, G. J. Protein Sci. 2022, 31(2), 396-406.
  • Toxicity and Immunogenicity of a Tardigrade Cytosolic Abundant Heat Soluble Protein in Mice
    Esterly, H. J.; Crilly, C. J.; Piszkiewicz, S.; Shovlin, D. J.; Pielak, G. J.; Christian, B. E. Front. Pharmacol. 2020, 11, 565969.