Jennifer Heemstra

Jen HeemstraBIOLOGICAL, ORGANIC, ANALYTICAL & MATERIALS CHEMISTRY

Associate Professor

Deputy Director, Center for Cell and Genome Science

B.S., University of California, Irvine, 2000
Ph.D., University of Illinois at Urbana-Champaign, 2005
Postdoctoral Fellow, Harvard University, 2007-2010

 

 

Phone:(801) 581-4191

Office: 1320B HEB-N

Email: heemstra@chem.utah.edu

Research Group

Biological Chemistry Program

Activities & Awards

  • W.W. Epstein Outstanding Educator Award, 2016
  • NSF CAREER Award, 2016
  • Cottrell Scholar Award, 2015
  • Myriad Award of Research Excellence, 2015
  • University of Utah College of Science Professorship, 2014
  • Army Research Office Young Investigator Award, 2011
  • Nelson J. Leonard ACS Division of Organic Chemistry Fellowship, 2004
  • Iota Sigma Pi Anne Louise Hoffman Award, 2004
  • Harry G. Drickamer Graduate Research Fellowship, 2003

Research Interests

Nature utilizes specific interactions between nucleic acids, proteins, and small molecules to direct all of the biological processes that make life possible. Inspired by these molecular recognition capabilities, the aim of our research program is twofold: (1) to engage in hypothesis driven research towards a deeper understanding of the forces that drive small molecule-nucleic acid and nucleic acid-nucleic acid interactions (2) to apply our understanding of these interactions towards the development of new technologies in biosensing, bioimaging, and antisense therapeutics.

DNA-Based Biosensors

Nucleic acid aptamers offer a promising alternative to antibodies for a wide range of biosensing applications. We have demonstrated the use of a split aptamer to transduce a small molecule signal into the output of a DNA ligation event. If present in solution, the target molecule directs assembly of the split aptamer, bringing DNA-appended reactive groups into close proximity and thus promoting a chemical ligation. We have demonstrated that this enables the sensitive and selective detection of drug molecules in an enzyme-linked format, which is the current gold standard in clinical diagnostics.  We have also addressed an overarching challenge in this field – the dearth of split aptamer recognition elements – by developing a reliable method for the engineering of aptamers into split aptamers.

Moving beyond detection to characterization, we seek to address the challenging task of measuring small molecule enantiopurity, as this is a key factor in the synthesis of pharmaceutical intermediates and other high-value chemicals. Enantiopurity can be measured by chiral chromatographic methods, but this process is limited to a few thousand samples per day.  Utilizing the principle of reciprocal chiral substrate selectivity, we have generated enantiomeric DNA biosensors capable of measuring small molecule enantiopurity with a direct fluorescence output, which provides significantly increased throughput. We envision application of this method to optimize stereoselectivity in reactions using either chemical or biological catalysts.

Fluorescent RNA Labeling

Thelocalization and dynamics of RNA play a key role in directing a wide variety ofcellular processes. Gaining a deeperunderstanding of mRNA localization patterns and the corresponding mechanisms ofmRNA transport would provide a wealth of information regarding diseaseprogression and potential therapeutic approaches. In collaboration with the Hollien Lab (Univ. of Utah Biology), we are developing a novel strategy for labeling and imaging of specific RNAs in living cells. Our method relies on the use of self-alkylating ribozymes, which can be fused to an RNA of interest and undergo covalent self-labeling with a fluorophore having an electrophilic reactive group. We envision using these ribozymes to track the localization of RNA in living cells and to identify the RNA-binding proteins that are responsible for RNA localization.

Modified Peptide Nucleic Acids

Peptide nucleic acid (PNA) is a nucleic acid analog in which the phosphodiester backbone is replaced with a peptide-like aminoethylglycine unit. PNA shows great potential for use in antisense and cellular imaging applications due to its higher affinity and selectivity for native nucleic acids as well as its increased resistance to degradation by nucleases and proteases. In order to expand the role of PNA in these applications, we are working to modify the backbone and investigate the subsequent effects on binding with DNA and RNA. Additionally, our research is aimed at improving cellular delivery of PNA through conjugation with nanoparticles. We anticipate that this research will produce PNA having improved pharmacokinetics as well as new capabilities as a therapeutic and imaging agent.

DNA-Based Micelles

Programmable materials capable of autonomous information processing can be generated by the fusion of a readable code to an output-producing functional material, and carries potential for use in applications including computing, biosensing, and nanotechnology. Our research aims to synthesize DNA-crosslinked micelles (DCMs) as a novel type of programmable materials capable of stimuli-responsive assembly and disassembly.

Selected Publications

  • Perera, R. T.; Fleming, A. M.; Peterson, A. M.; Heemstra, J. M.; Burrows, C. J.; White, H. S. Size-dependent unzipping of duplexes of A-form DNA-RNA, A-form DNA-PNA, and B-form DNA-DNA in the alpha-hemolysin nanopore. Biophys. J. 2015110, 306-314
  • Heemstra, J. M. Learning from the Unexpected in Life and DNA Self-Assembly. Beil. J. Org. Chem.201511, 2713-2720.
  • Peterson, A. M.; Jahnke, F. M.; Heemstra, J. M. Modulating the Substrate Selectivity of DNA Aptamers Using Surfactants. Langmuir201531, 11769-11773.
  • Peterson, A. M.; Tan, Z.; Kimbrough, E. M.; Heemstra, J. M. 3,3’-Dioctadecyloxacarbocyanine Perchlorate (DiO) as a Fluorogenic Probe for Measurement of Critical Micelle Concentration. Anal. Methods 2015, 7, 6877-6882
  • Anderton, G. I.; Bangerter, A. S.; Davis, T. C.; Feng, Z.; Furtak, A. J.; Larsen, J. O.; Scroggin, T. L.;  Heemstra, J. M. Accelerating Strain-Promoted Azide-Alkyne Cycloaddition using Micellar Catalysis. Bioconjugate Chem. 2015, 26, 1687-1691

  • Feagin, T. A.; Olsen, D. P. V.; Headman, Z. C.; Heemstra, J. M. High-Throughput Enantiopurity Analysis using Enantiomeric DNA-Based Sensors. J. Am. Chem. Soc. 2015137, 4198-4206.

  • Peterson, A. M.; Heemstra, J. M. Controlling Self-Assembly of DNA-Polymer Conjugates for Applications in Imaging and Drug Delivery.WIREs Nanomed. Nanobiotechnol., 20157, 282-297.

  • Sharma, A. K.; Plant, J. J.; Rangel, A. E.; Khoe, K. N.; Anamisis, A. J.; Hollien, J.; Heemstra, J. M. Fluorescent RNA Labeling Using Self-Alkylating Ribozymes. ACS Chem. Biol. 20149, 1680-1684.

  • De Costa, N. T. S.; Heemstra, J. M. Differential DNA and RNA Sequence Discrimination by PNA Having Charged Side Chains. Bioorg. Med. Chem. Lett.201424, 2360-2363.

  • Kent, A. D.; Spiropulos, N. G.; Heemstra, J. M. General Approach for Engineering Small-Molecule-Binding DNA Split Aptamers. Anal. Chem.2013, 85, 9916-9923.

  • De Costa, N. T. S.; Heemstra, J. M. Evaluating the Effect of Ionic Strength on Duplex Stability for PNA Having Negatively or Positively Charged Side Chains. PLoS ONE2013, 8, e58670.

  • Spiropulos, N. G.; Heemstra, J. M. Templating Effect in DNA Proximity Ligation Enables use of Non-Bioorthogonal Chemistry in Biological Fluids. Artificial DNA: PNA & XNA2012, 3, 123-128.

  • Feagin, T. A.; Shah, N. I.; Heemstra, J. M. Convenient and Scalable Synthesis of Fmoc-Protected Peptide Nucleic Acid Backbone. J. Nucleic Acids.2012, 2012, 354549.

  • Sharma, A. K.; Kent, A. D.; Heemstra, J. M. Enzyme-Linked Small-Molecule Detection using Split Aptamer Ligation. Anal. Chem.2012, 84, 6104-6109.

  • Sharma, A. K.; Heemstra, J. M. Small Molecule-Dependent Split Aptamer Ligation. J. Am. Chem. Soc. 2011, 133, 12426-12429.

  • Heemstra, J. M.; Liu, D. R. Templated Synthesis of Peptide Nucleic Acids via Sequence-Selective Base-Filling Reactions. J. Am. Chem. Soc. 2009, 131, 11347-11349.

  • Kowtoniuk, W. E.; Shen, Y.; Heemstra, J. M.; Agarwal, I.; Liu, D. R. A chemical screen for biological small molecule–RNA conjugates reveals CoA-linked RNA. Proc. Nat. Acad. Sci. U.S.A. 2009, 106, 7768-7773.

  • Heemstra, J. M.; Kerrigan, S. A.; Doerge, D. R.; Helferich, W. G.; Boulanger, W. A. Total Synthesis of (S)-Equol. Org. Lett. 2006, 8, 5441-5443.

  • Heemstra, J. M.; Moore, J. S. Enhanced Methylation Rate within a Foldable Molecular Receptor. J. Org. Chem. 2004, 69, 9234-9237.

  • Heemstra, J. M.; Moore, J. S. Helix stabilization through pyridinium-pi interactions. Chem. Commun. 2004, 1480-1481.

  • Heemstra, J. M.; Moore, J. S. A novel indicator series for measuring pKa values in acetonitrile. Tetrahedron2004, 60, 7287-7292.

  • Goto, H.; Heemstra, J. M.; Hill, D. J.; Moore, J. S. Single-Site Modifications and Their Effect on the Folding Stability of m-Phenylene Ethynylene Oligomers. Org. Lett. 2004, 6, 889-892.

  • Heemstra, J. M.; Moore, J. S. Pyridine-Containing m-Phenylene Ethynylene Oligomers Having Tunable Basicities. Org. Lett. 2004, 6, 659-662.

  • Heemstra, J. M.; Moore, J. S. Folding-Promoted Methylation of a Helical DMAP Analog. J. Am. Chem. Soc. 2004, 126, 1648-1649.

  • Cary (Heemstra), J. M.; Moore, J. S. Hydrogen Bond Stabilized Helix Formation of a m-Phenylene Ethynylene Oligomer. Org. Lett. 2002, 4, 4663-4666.

  • Nowick, J. S.; Cary (Heemstra), J. M.; Tsai, J. H. A Triply Templated Artificial beta-Sheet. J. Am. Chem. Soc. 2001, 123, 5176-5180.

Last Updated: 12/1/16