Shafaat, Hannah S.

Short Biography

Dr. Hannah Shafaat earned her B.S. in Chemistry from the California Institute of Technology (Caltech) in 2006, where she developed spectroscopic endospore viability assays with Dr. Adrian Ponce at the Jet Propulsion Laboratory and Professor Harry Gray. She earned her Ph.D. from the University of California, San Diego (UCSD) in 2011, under the direction of Professor Judy Kim, studying the structure and dynamics of amino acid radical intermediates in biological electron transfer reactions using spectroscopy. Following her graduate work, Hannah crossed the ocean to study hydrogenase and oxidase enzymes and learn advanced EPR techniques as a Humboldt Foundation Postdoctoral Fellow under Director Wolfgang Lubitz at the Max Planck Institute for Chemical Energy Conversion, in Mülheim an der Ruhr, Germany. Hannah began her independent research career at The Ohio State University in 2013, advancing from Assistant to Associate to Full Professor, and joined the UCLA faculty as a Professor in 2023.

Research Interests

Metal ions are found in approximately half of all proteins and are critical for the primary metabolism and all advanced functionality in higher organisms. Our research program seeks to understand how metalloenzymes work, for they catalyze small molecule activation reactions with rates, efficiencies, and selectivities that far surpass those of synthetic compounds. Some of the reactions that we are interested in include generation and oxidation of hydrogen (H2) gas, carbon dioxide (CO2) fixation, carbon-carbon bond formation to produce liquid fuels, and activation of dioxygen (O2) for functionalization of carbon-hydrogen bonds, within diverse classes of metalloproteins. We combine protein biochemistry and engineering with a diverse toolbox of bioinorganic techniques, including steady-state and time-resolved optical, vibrational, and magnetic spectroscopies, electrochemistry, computational methods, reactivity studies, and crystallography to gain mechanistic insight into these processes. With the wide array of techniques used across these projects, students in the group obtain skills that span multiple chemical and biological disciplines. Ultimately, we seek to establish fundamental structure-function correlations that enable the highly efficient reactivity seen in Nature, with impact and applications spanning from energy and environment to human health to origins of life and beyond.

Honors & Awards

  • Excellence in Undergraduate Research Mentoring Award (OSU), 2022
  • Kavli Fellow (Korean-American Kavli Frontiers of Science Symposium), 2019
  • Ed Stiefel Young Investigator Award (Metals in Biology GRC), 2019
  • National Institutes of Health R35 MIRA Award for New and Early Stage Investigators, 2018
  • Alfred P. Sloan Research Fellow in Chemistry, 2018
  • OSU University Laboratory Safety Committee Excellence in Safety Award, 2018
  • Department of Energy Office of Science Early Career Award, 2017
  • National Science Foundation CAREER Award, 2015

Representative Publications

Below is a list of selected publications:

  • Shafaat, H. S.; Manesis, A. C.; Yerbulekova, A. How to Build a Metalloenzyme: Lessons from a Protein-Based Model of Acetyl Coenzyme A Synthase. Chem. Res. 2023, 56, 984–993 DOI: 10.1021/acs.accounts.2c00824.
  • Grinter, R.; Kropp, A.; Venugopal, H.; Senger, M.; Badley, J.; Cabotaje, P. R.; Jia, R.; Duan, Z.; Huang, P.; Stripp, S. T.; et al. Structural basis for bacterial energy extraction from atmospheric hydrogen. Nature 2023, 615, 541–547 DOI: 1038/s41586-023-05781-7.
  • Treviño, R. E.; Shafaat, H. S. Protein-based models offer mechanistic insight into complex nickel metalloenzymes. Current Opinion in Chemical Biology 2022, 67, 102110 DOI: 1016/j.cbpa.2021.102110.
  • Manesis, A. C.; Yerbulekova, A.; Shearer, J.; Shafaat, H. S. Thioester synthesis by a designed nickel enzyme models prebiotic energy conversion. Natl. Acad. Sci. U. S. A. 2022, 119, e2123022119 DOI: 10.1073/pnas.2123022119.
  • Kisgeropoulos, E. C.; Gan, Y. J.; Greer, S. M.; Hazel, J. M.; Shafaat, H. S. Pulsed Multifrequency Electron Paramagnetic Resonance Spectroscopy Reveals Key Branch Points for One- vs Two-Electron Reactivity in Mn/Fe Proteins. Am. Chem. Soc. 2022, 144, 11991–12006 DOI: 10.1021/jacs.1c13738.
  • Shafaat, H. S.; Yang, J. Y. Uniting Biological and Chemical Strategies for Selective CO2 Reduction. Catalysis 2021, 4, 928–933 DOI: 10.1038/s41929-021-00683-1.
  • Naughton, K. J.; Treviño, R. E.; Moore, P. J.; Wertz, A. E.; Dickson, J. A.; Shafaat, H. S. In Vivo Assembly of a Genetically Encoded Artificial Metalloenzyme for Hydrogen Production. ACS Synth. Biol. 2021, 10, 2116–2120 DOI: 1021/acssynbio.1c00177.
  • Lewis, L. C.; Shafaat, H. S. Reversible Electron Transfer and Substrate Binding Support [NiFe3S4] Ferredoxin as a Protein-Based Model for [NiFe] Carbon Monoxide Dehydrogenase. Chem. 2021, 60, 13869–13875 DOI: 10.1021/acs.inorgchem.1c01323.
  • Kisgeropoulos, E. C.; Manesis, A. C.; Shafaat, H. S. Ligand Field Inversion as a Mechanism to Gate Bioorganometallic Reactivity: Investigating a Biochemical Model of Acetyl CoA Synthase Using Spectroscopy and Computation. Am. Chem. Soc. 2021, 143, 849–867 DOI: 10.1021/jacs.0c10135.
  • Gardner, E. J.; Marguet, S. C.; Cobb, C. R.; Pham, D. M.; Beringer, J. A. M.; Bertke, J. A.; Shafaat, H. S.; Warren, T. H. Uncovering Redox Non-innocent Hydrogen-Bonding in Cu(I)-Diazene Complexes. Am. Chem. Soc. 2021, 143, 15960–15974 DOI: 10.1021/jacs.1c04108.
  • Treviño, R. E.; Slater, J. W.; Shafaat, H. S. Robust Carbon-Based Electrodes for Hydrogen Evolution through Site-Selective Covalent Attachment of an Artificial Metalloenzyme. ACS Appl. Energy Mater. 2020, 3, 11099–11112 DOI: 1021/acsaem.0c02069.
  • Kisgeropoulos, E. C.; Griese, J. J.; Smith, Z. R.; Branca, R. M. M.; Schneider, C. R.; Högbom, M.; Shafaat, H. S. Key Structural Motifs Balance Metal Binding and Oxidative Reactivity in a Heterobimetallic Mn/Fe Protein. Am. Chem. Soc. 2020, 142, 5338–5354 DOI: 10.1021/jacs.0c00333.
  • Slater, J. W.; Marguet, S. C.; Gray, M. E.; Monaco, H. A.; Sotomayor, M.; Shafaat, H. S. Power of the Secondary Sphere: Modulating Hydrogenase Activity in Nickel-Substituted Rubredoxin. ACS Catal. 2019, 9, 8928–8942 DOI: 1021/acscatal.9b01720.
  • Schneider, C. R.; Lewis, L. C.; Shafaat, H. S. The good, the neutral, and the positive: buffer identity impacts CO 2 reduction activity by nickel( ii ) cyclam. Dalton Transactions 2019, 48, 15810–15821 DOI: 1039/C9DT03114F.
  • Manesis, A. C.; Musselman, B. W.; Keegan, B. C.; Shearer, J.; Lehnert, N.; Shafaat, H. S. A Biochemical Nickel(I) State Supports Nucleophilic Alkyl Addition: A Roadmap for Methyl Reactivity in Acetyl Coenzyme A Synthase. Chem. 2019, 58, 8969–8982 DOI: 10.1021/acs.inorgchem.8b03546.
  • Slater, J. W.; Marguet, S. C.; Monaco, H. A.; Shafaat, H. S. Going beyond Structure: Nickel-Substituted Rubredoxin as a Mechanistic Model for the [NiFe] Hydrogenases. Am. Chem. Soc. 2018, 140, 10250–10262 DOI: 10.1021/jacs.8b05194.
  • Schneider, C. R.; Manesis, A. C.; Stevenson, M. J.; Shafaat, H. S. A photoactive semisynthetic metalloenzyme exhibits complete selectivity for CO2 reduction in water. Commun. 2018, 54, 4681–4684 DOI: 10.1039/C8CC01297K.
  • Maugeri, P. T.; Griese, J. J.; Branca, R. M.; Miller, E. K.; Smith, Z. R.; Eirich, J.; Högbom, M.; Shafaat, H. S. Driving Protein Conformational Changes with Light: Photoinduced Structural Rearrangement in a Heterobimetallic Oxidase. Am. Chem. Soc. 2018, 140, 1471–1480 DOI: 10.1021/jacs.7b11966.