About

Michael E. Harris is a Professor in the Department of Chemistry at the University of Florida. His research focuses on addressing fundamentally important questions in RNA biology and enzyme mechanism, specifically investigating how Nature utilizes the physical properties of RNA to achieve catalysis, predicting the specificity of enzymes and proteins that bind to RNA, and leveraging this understanding to contribute to the development of novel therapeutics. To pursue these goals, his lab employs a range of tools including high throughput enzymology, rapid reaction kinetics, and spectroscopy, and engages in synergistic collaborations that integrate structural biology, computation, and medicinal chemistry. The long-term vision of his research is to enhance understanding of RNA catalysis, develop broadly useful models of RNA specificity, and realize novel opportunities in drug discovery. Professor Harris received his B.S. in Chemistry from Florida State University in 1986, followed by a PhD in Biochemistry from the University of Alabama at Birmingham in 1992 under the mentorship of Stephen Hajdu. He then completed postdoctoral training at Indiana University in the lab of Norman Pace from 1992 to 1996. Prior to his current position, he served as an Associate Professor in the Department of Biochemistry at Case Western Reserve University School of Medicine from 2002 to 2014.

Research topics

• Biochemistry
• Chemistry
• Biology
• Biophysics
• Stereochemistry
• Materials science
• Genetics
• Physics
• Nanotechnology

Selected publications

• Assay-Based High Throughput Screening of Diverse Libraries Identifies Selective Inhibitors of <i>Staphylococcus aureus</i> Ribonuclease P

  ACS Chemical Biology · 2026-04-29

  articleSenior author

  . Thus, expanding assay-based screening into broader chemical space can reveal novel scaffolds as potential starting points for the development of selective inhibitors targeting an essential bacterial RNA processing enzyme.

  PublisherDOI

• Closing the loop – the chemistry of depolymerisation, polymer recycling and environmental degradation: general discussion

  Faraday Discussions · 2025-12-08

  article

  Jake L. Nicholson opened the discussion of the paper by Derek J. Irvine: When you use 2PP for additive manufacturing, is it more optimal to work with opaque or transparent materials to minimize charring of the material? Derek J. Irvine responded: It is typically better for accuracy of printing to use transparent

  PublisherDOI

• Novel feedstocks: general discussion

  Faraday Discussions · 2025-12-12

  article

  Kyoko Nozaki opened the discussion of the introductory Spiers Memorial Lecture by Marc A. Hillmyer: Did you measure BOD (biological oxygen demand) for the new polymers? I heard that carbon atoms of the polymers must be fully degraded to CO2 to avoid any residuals. Marc A. Hillmyer answered: We have not done those

  PublisherDOI

• Selective Synthesis of Unsaturated Imines via [py2TiI2(NPh)]2-Catalyzed Alkyne Carboamination

  ChemRxiv · 2025-05-16

  preprintOpen access1st authorCorresponding

  Strongly Lewis acidic titanium iodo complexes catalyze selective inter- and intramolecular carboamination of alkynes to give unsaturated imines. Computations and mechanistic experiments indicate that unsaturated imines are not the direct product of alkyne carboamination as previously reported, but result from the ring-opening rearrangement of cyclopropylimines instead. Reactions of cyclopropylimines with titanium complexes confirm the generation of acyclic imines from an iminocyclopropane rearrangement, however it is noted that this rearrangement is specific to titanium-iodide species.

  PublisherOA PDFDOI

• Catalysis: general discussion

  Faraday Discussions · 2025-12-10

  article

  Arianna Brandolese opened a discussion of the paper by Debashis Chakraborty: Have you tested the chiral catalysts in kinetic-resolution polymerizations? Debashis Chakraborty replied: No. Arianna Brandolese asked: Have you tested more hindered epoxides, such as limonene oxide? Debashis Chakraborty responded: No, w

  PublisherDOI

• A minimal RNA substrate with dual fluorescent probes enables rapid kinetics and provides insight into bacterial RNase P active site interactions

  RSC Chemical Biology · 2024-01-01

  articleOpen accessSenior authorCorresponding

  is due to inability to engage U69. These studies establish a set of experimental tools to analyze RNase P kinetics and mechanism and can be expanded to gain new insights into the assembly of the active RNase P-ptRNA complex.

  PublisherOA PDFDOI

• Rapid Ribonuclease P Kinetics Measured by Stopped-Flow Fluorescence and Fluorescence Anisotropy

  Methods in molecular biology · 2024-01-01 · 3 citations

  articleSenior author
  PublisherDOI

• Alternative substrate kinetics of SARS-CoV-2 Nsp15 endonuclease reveals a specificity landscape dominated by RNA structure

  Nucleic Acids Research · 2024-10-30 · 4 citations

  articleOpen accessSenior author

  Coronavirus endoribonuclease Nsp15 contributes to the evasion of host innate immunity by suppressing levels of viral dsRNA. Nsp15 cleaves both ssRNA and dsRNA in vitro with a strong preference for unpaired or bulged U residues, and its activity is stimulated by divalent ions. Here, we systematically quantified effects of RNA sequence and structure context that define its specificity. The results show that sequence preference for U↓A/G, observed previously, contributes only ca. 2-fold to kcat/Km. In contrast, dsRNA structure flanking a bulged U residue increases kcat/Km by an order of magnitude compared to ssRNA while base pairing in dsRNA essentially blocks cleavage. Despite enormous differences in multiple turnover kinetics, the effect of RNA structure on the cleavage step is minimal. Surprisingly, although divalent ion activation of Nsp15 is widely considered to be important for its biological function, the effect on kcat/Km is only ∼2-fold and independent of RNA structure. These results reveal a specificity landscape dominated by RNA structure and provide a quantitative framework for identifying interactions that underlie specificity, determining mechanisms of inhibition and resistance and defining targets important for coronavirus biology.

  PublisherDOI

• Rapid Kinetics of Pistol Ribozyme: Insights into Limits to RNA Catalysis

  Biochemistry · 2023-06-09 · 5 citations

  articleOpen accessSenior authorCorresponding

  Pistol ribozyme (Psr) is a distinct class of small endonucleolytic ribozymes, which are important experimental systems for defining fundamental principles of RNA catalysis and designing valuable tools in biotechnology. High-resolution structures of Psr, extensive structure–function studies, and computation support a mechanism involving one or more catalytic guanosine nucleobases acting as a general base and divalent metal ion-bound water acting as an acid to catalyze RNA 2′-O-transphosphorylation. Yet, for a wide range of pH and metal ion concentrations, the rate of Psr catalysis is too fast to measure manually and the reaction steps that limit catalysis are not well understood. Here, we use stopped-flow fluorescence spectroscopy to evaluate Psr temperature dependence, solvent H/D isotope effects, and divalent metal ion affinity and specificity unconstrained by limitations due to fast kinetics. The results show that Psr catalysis is characterized by small apparent activation enthalpy and entropy changes and minimal transition state H/D fractionation, suggesting that one or more pre-equilibrium steps rather than chemistry is rate limiting. Quantitative analyses of divalent ion dependence confirm that metal aquo ion pKa correlates with higher rates of catalysis independent of differences in ion binding affinity. However, ambiguity regarding the rate-limiting step and similar correlation with related attributes such as ionic radius and hydration free energy complicate a definitive mechanistic interpretation. These new data provide a framework for further interrogation of Psr transition state stabilization and show how thermal instability, metal ion insolubility at optimal pH, and pre-equilibrium steps such as ion binding and folding limit the catalytic power of Psr suggesting potential strategies for further optimization.

  PublisherOA PDFDOI

• A general and efficient approach to synthesize the phosphoramidites of 5′- ¹⁸ <i>O</i> labeled purine nucleosides

  Nucleosides Nucleotides & Nucleic Acids · 2023-05-26 · 1 citations

  articleOpen access

  5′-18O labeled RNA oligos are important probes to investigate the mechanism of 2′-O-transphosphorylation reactions. Here we describe a general and efficient synthetic approach to the phosphoramidite derivatives of 5′-18O labeled nucleosides starting from the corresponding commercially available 5′-O-DMT protected nucleosides. Using this method, we prepared 5′-18O-guanosine phosphoramidite in 8 steps (13.2% overall yield), 5′-18O-adenosine phosphoramidite in 9 steps (10.1% overall yield) and 5′-18O-2′-deoxyguanosine phosphoramidite in 6 steps (12.8% overall yield). These 5′-18O labeled phosphoramidites can be incorporated into RNA oligos by solid phase synthesis for determination of heavy atom isotope effects in RNA 2′-O-transphosphorylation reactions.

  PublisherOA PDFDOI

Recent grants

• NIH Grant F32GM015979

  NIH · $81k

• NIH Grant S10RR014923

  NIH · $147k · 2001

• Specificity in Substrate Recognition and Catalysis by RNA Processing Enzymes

  NIH · $1.6M · 2018–2025

• Enzymatic Activation of Water

  NSF · $506k · 2007–2011

• Analysis of RNA-metal ion interactions by solution Raman spectroscopy

  NSF · $450k · 2011–2014

Frequent coauthors

• Darrin M. York

  Quantitative BioSciences

  99 shared

• Joseph A. Piccirilli

  University of Chicago

  88 shared

• Vernon Anderson

  Children's Hospital of Philadelphia

  67 shared

• K. Y. Wong

  Prince of Wales Hospital

  56 shared

• Eric L. Christian

  Case Western Reserve University

  54 shared

• Hong Gu

  Peking University

  43 shared

• Shuming Zhang

  33 shared

• Adam G. Cassano

  Drew University

  30 shared

Education

• postdoctoral, Biology

  Indiana University Bloomington

• PhD, Biochemistry

  University of Alabama at Birmingham

• BS, Chemistry

  Florida State University