JENNIFER M HEEMSTRA portrait
  • Deputy Director, Center for Cell and Genome Science
  • Associate Professor, Chemistry
801-581-4191

Research Statement

Overview

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

We have recently demonstrated the use of a split aptamer to transduce a small molecule signal (in this case cocaine) into the output of DNA ligation. If present in solution, cocaine directs assembly of the split aptamer, bringing DNA-appended reactive groups into close proximity and thus promoting a chemical ligation. The ligation chemistry utilized is strain-promoted azide-alkyne cycloaddition, as azides and cyclooctynes are orthogonal to common biological functional groups and the reaction does not require exogenous reagents. Research is underway to utilize this technology for the development of small-molecule detection assays.

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.

Research Keywords

  • Nucleic Acids
  • Nanoparticles
  • Molecular Imaging
  • Biosensors

Presentations

  • 252nd ACS National Meeting, “Tuning the chemical properties of XNA nucleotides and oligomers for therapeutics and diagnostics,” Philadelphia, PA, August 2016. Invited Talk/Keynote, Presented, 08/2016.
  • Pacifichem 2015, “Small-molecule detection and enantiopurity measurement using DNA-based sensors,” Honolulu, HI, December 2015. Invited Talk/Keynote, Presented, 12/2015.
  • Pacifichem 2015, “Fluorescent RNA labeling using self-alkylating ribozymes,” Honolulu, HI, December 2015. Invited Talk/Keynote, Presented, 12/2015.
  • Tan, Z.; Feagin, T. A. Heemstra, J. M. Temporal Control of Aptamer Biosensors Using an Equilibrium-Shifting Photocleavable Linker. nanoUtah Nanotechnology Conference, Salt Lake City, UT, October 2015. Poster, Presented, 10/2015.
  • Peterson, A. M.; Jahnke, F. M. Heemstra, J. M. Modulating the Substrate Selectivity of DNA Aptamers Using Surfactants. nanoUtah Nanotechnology Conference, Salt Lake City, UT, October 2015. Poster, Presented, 10/2015.
  • 21st Annual Cottrell Scholar Conference, “What do we want our students to become?” Tucson, AZ, July 2015. Invited Talk/Keynote, Presented, 07/2015.
  • Feagin, T. A.; Heemstra, J. M. High-throughput enantiopurity analysis using enantiomeric DNA-based sensors. 2015 ACS Northwest Regional Meeting, Pocatello, ID, June 2015. Contributed Talk, Presented, 06/2015.
  • Feagin, T. A.; Heemstra, J. M. High-throughput Enantiopurity Analysis using Enantiomeric DNA-Based Sensors. Nucleosides, Nucleotides & Oligonucleotides Gordon Research Seminar, Newport, RI, June 2015. Contributed Talk, Presented, 06/2015.
  • Rangel, A. E.; Sharma, A. K.; Plant, J. J.; Meek, K. N.; Anamisis, A. J.#; Hollien, J.; Heemstra, J. M. Developing and Exploring the Substrate Scope of a Self-Alkylating Ribozyme for Fluorescent mRNA Labeling. Nucleosides, Nucleotides & Oligonucleotides Gordon Research Seminar, Newport, RI, June 2015. Contributed Talk, Presented, 06/2015.
  • Nucleosides, Nucleotides & Oligonucleotides Gordon Research Conference, “Small-Molecule Detection and Enantiopurity Measurement Using DNA-Based Sensors,” Newport, RI, June 2015. Invited Talk/Keynote, Presented, 06/2015.
  • Anamisis, A. J.#; Sharma, A. K.; Plant, J. J.; Rangel, A. E.; Meek, K. N.; Hollien, J.; Heemstra, J. M. Covalent mRNA labeling using Fluorescently Self‐Alkylating Ribozymes. Nucleosides, Nucleotides & Oligonucleotides Gordon Research Conference, Newport, RI, June 2015. Poster, Presented, 06/2015.
  • Feagin, T. A.; Heemstra, J. M. High-throughput Enantiopurity Analysis using Enantiomeric DNA-Based Sensors. Nucleosides, Nucleotides & Oligonucleotides Gordon Research Conference, Newport, RI, June 2015. Poster, Presented, 06/2015.
  • Meek, K. N.; Rangel, A. E.; Heemstra, J. M. Parallel Generation of DNA and RNA aptamers for Maltose Binding Protein. Nucleosides, Nucleotides & Oligonucleotides Gordon Research Conference, Newport, RI, June 2015. Poster, Presented, 06/2015.
  • Meek, K. N.; Rangel, A. E.; Heemstra, J. M. Parallel Generation of DNA and RNA aptamers for Maltose Binding Protein. Nucleosides, Nucleotides & Oligonucleotides Gordon Research Seminar, Newport, RI, June 2015. Poster, Presented, 06/2015.
  • Rangel, A. E.; Sharma, A. K.; Plant, J. J.; Meek, K. N.; Anamisis, A. J.#; Hollien, J.; Heemstra, J. M. Developing and Exploring the Substrate Scope of a Self-Alkylating Ribozyme for Fluorescent mRNA Labeling. Nucleosides, Nucleotides & Oligonucleotides Gordon Research Conference, Newport, RI, June 2015. Poster, Presented, 06/2015.
  • Kent, A. D.#; Spiropulos, N. G.; Heemstra, J. M. General Approach for Engineering Small-Molecule-Binding DNA Split Aptamers. University of Utah Undergraduate Research Symposium, Salt Lake City, UT, April 2015. Contributed Talk, Presented, 04/2015.
  • Invited seminar at University of California, Berkeley. Invited Talk/Keynote, Presented, 04/2015.
  • Invited seminar at University of California, Davis. Invited Talk/Keynote, Presented, 04/2015.
  • Kimbrough, E. M.#; Peterson, A. M.; Tan, Z.; Heemstra, J. M. Determination of Critical Micelle Concentrations Using a New Solvatochromatic Dye. University of Utah Undergraduate Research Symposium, Salt Lake City, UT, April 2015. Poster, Presented, 04/2015.
  • Invited seminar at University of Illinois, Urbana-Champaign. Invited Talk/Keynote, Presented, 03/2015.
  • Invited seminar at University of Toledo. Invited Talk/Keynote, Presented, 03/2015.
  • Invited seminar at University of Detroit Mercy. Invited Talk/Keynote, Presented, 03/2015.
  • IUPAC 10th International Conference on Bio-Organic Chemistry, “Small-Molecule Detection and Enantiopurity Measurement using DNA-Based Sensors,” Pune, India, January 2015. Invited Talk/Keynote, Presented, 01/2015.
  • Kent, A. D.#; Spiropulos, N. G.; Heemstra, J. M. General Approach for Engineering Small-Molecule-Binding DNA Split Aptamers. Research Posters on the Hill, Salt Lake City, UT, January 2015. Poster, Presented, 01/2015.
  • Kent, A. D.#; Spiropulos, N. G.; Heemstra, J. M. General Approach for Engineering Small-Molecule-Binding DNA Split Aptamers. National Collegiate Research Conference, Cambridge, MA, January 2015. Poster, Presented, 01/2015.
  • 248th ACS National Meeting, “Are you always this enthusiastic?,” (Special symposium on career-life balance) San Francisco, CA, August 2014. Invited Talk/Keynote, Presented, 08/2014.
  • Invited Chemistry seminar at Carnegie Mellon University. Invited Talk/Keynote, Presented, 11/2013.
  • Invited Chemistry seminar at Pacific University. Invited Talk/Keynote, Presented, 10/2013.
  • Invited Chemistry seminar at Boise State University. Invited Talk/Keynote, Presented, 10/2013.
  • De Costa, N. T. S.; Heemstra, J. M. Tailoring peptide nucleic acids to electrostatically mimic DNA and RNA. 246th ACS National Meeting, Indianapolis, IN, September 2013. Contributed Talk, Presented, 09/2013.
  • 246th ACS National Meeting, “Small-molecule detection using DNA assembly-driven reactions,” Indianapolis, IN, September 2013. Invited Talk/Keynote, Presented, 09/2013.
  • University of Oregon Materials and Optical Symposium, “DNA-based biosensors using small-molecule-directed macromolecular assembly and disassembly,” Eugene, OR, September 2013. Invited Talk/Keynote, Presented, 09/2013.
  • Invited MRSEC seminar at University of Massachusetts, Amherst. Invited Talk/Keynote, Presented, 06/2013.
  • Santa Clara University, October 2011. Invited Talk/Keynote, Presented, 10/2011.
  • Pacific Lutheran University, October 2011. Invited Talk/Keynote, Presented, 10/2011.
  • Tufts University, July 2011. Invited Talk/Keynote, Presented, 07/2011.
  • Sharma, A. K; Heemstra, J. M. Small Molecule-Dependent Split Aptamer Ligation. Nucleosides, Nucleotides & Oligonucleotides Gordon Research Conference, Newport, RI, July 2011 . Poster, Presented, 07/2011.
  • Brigham Young University, Idaho, January 2011. Invited Talk/Keynote, Presented, 01/2011.
  • Bioscience Symposium, “AuNP-PNA conjugates: targeting miRNA for potential imaging and treatment of breast cancer,” University of Utah, September 2010. Invited Talk/Keynote, Presented, 09/2010.

Research Groups

  • Erika Feten, Undergraduate Student. 12/2016 - present.
  • Satheesh Ellipilli, Postdoc. 10/2016 - present.
  • Miguel Pereira, Postdoc. 09/2016 - present.
  • Misael Romero, Graduate Student. 08/2016 - present.
  • Hershel Lackey, Graduate Student. 08/2016 - present.
  • Brad Green, Postdoc. 07/2016 - present.
  • Riley Giesler, Graduate Student. 06/2016 - present.
  • Amberlyn Peterson, Postdoc. 04/2016 - present.
  • Karl Grimm, Undergraduate Student. 01/2016 - 05/2016.
  • John Lynn, Undergraduate Student. 01/2016 - 05/2016.
  • Yan Jiang, Undergraduate Student. 01/2016 - 05/2016.
  • Amanda Shepherd, Undergraduate Student. 01/2016 - 05/2016.
  • Katie Jones, Undergraduate Student. 09/2015 - present.
  • Tewoderos Ayele, Graduate Student. 06/2015 - present.
  • Colin Swenson, Graduate Student. 05/2015 - present.
  • Yu Zhang, Undergraduate Student. 05/2015 - 07/2015.
  • Erin Price, Undergraduate Student. 01/2015 - present.
  • Sabrina Aderibigbe, Undergraduate Student. 01/2015 - 05/2015.
  • Derek Davis, Undergraduate Student. 01/2015 - 05/2015.
  • Maureen Larkin, Undergraduate Student. 01/2015 - 05/2015.
  • Grand Anderton, Undergraduate Student. 01/2015 - 05/2015.
  • Petr Simon, Postdoc. 11/2014 - 11/2015.
  • Zhe Chen, Postdoc. 08/2014 - 08/2016.
  • Zhesen Tan, Graduate Student. 10/2013 - present.
  • Evelyn Kimbrough, Undergraduate Student. 09/2013 - present.
  • April Anamisis, Undergraduate Student. 09/2013 - 08/2016.
  • Zachary Headman, Undergraduate Student. 04/2013 - 12/2014.
  • Alexandra Rangel, Graduate Student. 02/2013 - present.

Publications

  • Hanson WM, Chen Z, Jackson LK, Attaf M, Sewell AK, Heemstra JM & Phillips JD (2016). Reversible Oligonucleotide Chain Blocking Enables Bead Capture and Amplification of T-Cell Receptor α and β Chain mRNAs. Journal of the American Chemical Society. Vol. 138, 11073-6. Published, 09/01/2016.
  • Meek KN, Rangel AE & Heemstra JM (2016). Enhancing aptamer function and stability via in vitro selection using modified nucleic acids. Methods (San Diego, Calif.). Vol. 106, 29-36. Published, 08/01/2016.
  • Chen Z, Meek KN, Rangel AE & Heemstra JM (2016). Synthesis and polymerase incorporation of β,γ-modified α-l-threofuranosyl thymine triphosphate mimics. Bioorganic & Medicinal Chemistry Letters. Vol. 26, 3958-62. Published, 08/01/2016.
  • Davis DL, Price EK, Aderibigbe SO, Larkin MX, Barlow ED, Chen R, Ford LC, Gray ZT, Gren SH, Jin Y, Keddington KS, Kent AD, Kim D, Lewis A, Marrouche RS, O'Dair MK, Powell DR, Scadden MH, Session CB, Tao J, Trieu J, Whiteford KN, Yuan Z, Yun G, Zhu J & Heemstra JM (2016). Effect of Buffer Conditions and Organic Cosolvents on the Rate of Strain-Promoted Azide-Alkyne Cycloaddition. The Journal of Organic Chemistry. Vol. 81, 6816-9. Published, 08/01/2016.
  • Tan Z, Feagin TA & Heemstra JM (2016). Temporal Control of Aptamer Biosensors Using Covalent Self-Caging To Shift Equilibrium. Journal of the American Chemical Society. Vol. 138, 6328-31. Published, 05/01/2016.
  • Perera RT, Fleming AM, Peterson AM, Heemstra JM, Burrows CJ & White HS (2016). Unzipping of A-Form DNA-RNA, A-Form DNA-PNA, and B-Form DNA-DNA in the α-Hemolysin Nanopore. Biophysical Journal. Vol. 110, 306-14. Published, 01/01/2016.
  • Heemstra, J. M. Learning from the Unexpected in Life and DNA Self-Assembly. Beil. J. Org. Chem. 2015 11, 2713-2720. Published, 12/2015.
  • Peterson AM, Jahnke FM & Heemstra JM (2015). Modulating the Substrate Selectivity of DNA Aptamers Using Surfactants. Langmuir. Vol. 31, 11769-73. Published, 11/01/2015.
  • Anderton GI, Bangerter AS, Davis TC, Feng Z, Furtak AJ, Larsen JO, Scroggin TL & Heemstra JM (2015). Accelerating Strain-Promoted Azide-Alkyne Cycloaddition Using Micellar Catalysis. Bioconjugate Chemistry. Vol. 26, 1687-91. Published, 08/01/2015.
  • 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. Published, 07/2015.
  • Peterson AM & Heemstra JM (2015). Controlling self-assembly of DNA-polymer conjugates for applications in imaging and drug delivery. Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology. Vol. 7, 282-97. Published, 04/01/2015.
  • Feagin TA, Olsen DP, Headman ZC & Heemstra JM (2015). High-throughput enantiopurity analysis using enantiomeric DNA-based sensors. Journal of the American Chemical Society. Vol. 137, 4198-206. Published, 04/01/2015.
  • 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. 2014 9, 1680-1684. Published, 06/2014.
    http://pubs.acs.org/doi/abs/10.1021/cb5002119
  • De Costa, N. T. S.; Heemstra, J. M. Differential DNA and RNA Sequence Discrimination by PNA Having Charged Side Chains. Bioorg. Med. Chem. Lett. 2014 24, 2360-2363. Published, 05/2014.
    http://www.sciencedirect.com/science/article/pii/S...
  • 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. Published, 09/2013.
  • 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 ONE 2013 8, e58670. Published, 02/2013.
  • Spiropulos, N. G.; Heemstra, J. M. Templating Effect in DNA Proximity Ligation Enables use of Non-Bioorthogonal Chemistry in Biological Fluids. Artificial DNA: PNA & XNA 2012 3, 123-128. Published, 02/2013.
  • Sharma, A. K.; Heemstra, J. M. Small Molecule-Dependent Split Aptamer Ligation. J. Am. Chem. Soc. 2011, 133, 12426-12429. Published, 07/16/2011.
    http://pubs.acs.org/doi/abs/10.1021/ja205518e