Professor, Department of Pharmaceutical Sciences
School of Pharmacy & Pharmaceutical Sciences

Chemical Biology, Synthetic Biology, Polymerase Engineering, Oligonucleotide Therapeutics

Lab Website

Distinguished Mid-Career Faculty Award for Research (UCI Senate, 1 per year, 2022)
Selected speaker at the UCI Chief Executive Roundtable Meeting (2022)
Athalie R. Clarke Achievement Award (2021)
AAAS Fellow (2018)
Sigma Xi (2018)
W.M. Keck Foundation Awardee (2018)
ASU Faculty Award for Excellence in Defining Edge Research (2014)
Arizona Technology Enterprise Achievement Award (2013 – 2014)
National Institutes of Health EUREKA Award (2008-2012)
Howard Hughes Medical Institute Postdoctoral Fellowship (2001 – 2004)
University of California, Riverside, Graduate Fellowship (1994 – 2000)
National Collegiate Science Award (1994)

HHMI Postdoctoral Fellow, Harvard Medical School (2000-2004) with Jack Szostak

My lab seeks to harness artificial genetic polymers (XNAs) as a foundation for creating fundamentally new capabilities in synthetic biology and healthcare. This effort is organized around three mutually reinforcing research pillars. First, we utilize advanced microfluidic platforms to evolve enzymes that do not exist in nature, including polymerases capable of replicating chemically diverse classes of XNAs. Second, we reconstruct and interrogate the evolutionary pathways that gave rise to these activities, integrating biochemical, genetic, and structural approaches to uncover general principles of protein evolution that remain inaccessible to current predictive models. Third, we deploy these engineered enzymes as enabling tools for practical healthcare applications, including amplification-free diagnostics, nucleic acid enzymes for durable, allele-specific gene silencing, and functionalized therapeutic aptamers with enhanced pharmacological properties. Together, this work establishes a unified framework for transforming artificial genetic systems into robust molecular technologies with a direct and lasting impact on human health.

Medina EL, Maola VA, Hajjar M, Ko GK, Ho EJ, Horton AR, Chim N, and Chaput JC* 2026. Rapid evolution of an RNA polymerase with broad substrate repertoire. Nature Chemical Biology. https://doi.org/10.1038/s41589-025-02124-7.

Maola VA, Lee JJ, Holguin MJ, Quijano RN, Nguyen KK, Ho KL, Medina JV, Botello-Cornejo E, Barpuzary B, Chim N, and Chaput JC* 2025. Directed evolution of a TNA polymerase identifies independent paths to fidelity and catalysis. Nature Communications doi.org/10.1038/s41467-025-67652-1.

Yu H, Zhang S, and Chaput JC* 2012. Darwinian evolution of an alternative genetic system provides support for TNA as an RNA progenitor. Nat. Chem. 4, 183-187.

Pinheiro VB, Taylor AI, Cozens C, Abramov M, Renders M, Zhang S, Chaput JC, Wengel J, Peak-Chew SY, McLaughlin SH, Herdewijn P, and Holliger P* 2012. Synthetic genetic polymers capable of heredity and evolution. Science 336, 341-344.

Larsen AC, Dunn MR, Hatch A, Sau SP, Youngbull C, and Chaput JC* 2016. A general strategy for expanding polymerase function by droplet microfluidics. Nat. Commun. 7, 11235.

Chim N, Shi C, Sau SP, Nikoomanzar A, and Chaput JC* 2017. Structural basis for TNA synthesis by an engineered TNA polymerase. Nat. Commun. 8, 1810.

Wang Y, Ngor AK, Nikoomanzar A, and Chaput JC* 2018. Evolution of a general RNA-cleaving FANA enzyme. Nat. Commun. 9, 5067.

Wang Y, Nguyen K, Spitale RC, and Chaput JC* 2021. A biologically stable DNAzyme that efficiently silences gene expression in cells. Nat. Chem. 13, 319-326.

Chim N, Meza RA, Trinh AM, Yang K, and Chaput JC* 2021. Following replicative DNA synthesis by time-resolved X-ray crystallography. Nat. Commun. 12: 2641.

Maola VA, Yik EJ, Hajjar M, Lee JJ, Holguin MJ, Quijano RN, Nguyen KK, Ho KL, Medina JV, Chim N, and Chaput JC* 2024. Directed evolution of a highly efficient TNA polymerase achieved by homologous recombination. Nature Catalysis. 7, 1173-1185.

Nguyen K, Malik TN, and Chaput, JC* 2023. Chemical evolution of an autonomous DNAzyme with allele-specific gene silencing activity. Nature Commun. 14, 2413.

American Chemical Society (ACS)

American Association for the Advancement of Science (AAAS)

Professor
Arizona State University 2014—2015

Associate Professor
Arizona State University 2011—2014

Assistant Professor
Arizona State University 2005—2011

Cellular and Molecular Biosciences

Chemical Biology

Chemistry

Pharmacological Sciences

Link to this profile
https://faculty.uci.edu/profile/?facultyId=6145

Last updated
01/12/2026