John Charles Chaput

picture of John Charles Chaput

Professor, Pharmaceutical Sciences
Pharmaceutical Sciences

Ph.D., University of California, Riverside, 2000, Chemistry
M.S., University of California, Riverside, 1995, Chemistry
B.S., Creighton University, 1994, Chemistry

Email: jchaput@uci.edu

University of California, Irvine

Irvine, CA 92697
Research Interests
Chemical Biology, Synthetic Biology, Polymerase Engineering, Artificial Genetic Polymers
URL
Academic Distinctions
AAAS Fellow (2018)
Sigma Xi (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)
Appointments
HHMI Postdoctoral Fellow, Harvard Medical School (2000-2004) with Jack Szostak
Research Abstract
We are interested in evolving enzymes (polymerases, ligases, kinases, and nucleases) that can synthesize and modify artificial genetic polymers (XNAs) in the same way that natural enzymes synthesize and process DNA and RNA. Our goal is to use these enzymes to study the synthetic biology of artificial genetic polymers so that we can: 1) improve our understanding of how enzymes work, 2) investigate fundamental questions about life's genetic system, and 3) establish new diagnostic and therapeutic agents that improve human health and disease detection. This is a highly interdisciplinary environment where students learn state-of-the-art techniques in synthetic organic chemistry, microfluidics, X-ray crystallography, and directed evolution, and apply this knowledge to innovative projects that advance the emerging field of synthetic genetics.

Some of the questions we wish to answer include:
1. Why did nature choose DNA (and RNA) as the molecular basis of life's genetic system?
2. What are the determinants of polymerase specificity and how can this information be used to generate engineered polymerases that are highly efficient and specific for XNA substrates?
3. Can we engineer XNA polymerases that can amplify XNA using the polymerase chain reaction?
4. Can we evolve a new generation of affinity reagents (aptamers) that are better equipped for protein or small molecule binding in biological environments?
5. Can we advance the development of XNA enzymes--XNA molecules that fold themselves into shapes with catalytic activity--to a point where they can be used in practical applications, like gene silencing?
Publications
Selected Publications:
1. Wang, Y., Ngor, A., Nikoomanzar, A., and Chaput, J.C.* 2018. Evolution of a general RNA-cleaving FANA Enzyme. Nature Communications 9, 5067.

2. Pinheiro, V.B., Taylor, A.I., Cozens, C., Abramov, M., Renders, M., Zhang. S., Chaput, J.C., Wengel, J., Peak-Chew, S-Y., McLaughlin, S.H., Herdewijn, P., and Holliger, P.* 2012. Synthetic genetic polymers capable of heredity and evolution. Science 336, 341-344.

3. Yu, H., Zhang, S., and Chaput, J.C.* 2012. Darwinian evolution of an alternative genetic system provides support for TNA as an RNA progenitor. Nature Chemistry 4, 183-187.

4. Chim, N., Shi, C., Sau, S., Nikoomanzar, A., and Chaput, J.C.* 2017. Structural basis for TNA synthesis by an engineered TNA polymerase. Nat. Commun. 8, 1810.
Professional Societies
American Chemical Society (ACS)
American Association for the Advancement of Science (AAAS)
Other Experience
Professor
Arizona State University 2014—2015

Associate Professor
Arizona State University 2011—2014

Assistant Professor
Arizona State University 2005—2011

Graduate Programs
Pharmacological Sciences

Chemistry

Chemical Biology

Cellular and Molecular Biosciences

Last updated
12/28/2018