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Nicholas Stephanopoulos

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School of Molecular Sciences
Associate Professor
Faculty, TEMPE Campus, Mailcode 7301
Biodesign Center for Molecular Design & Biomimetics
Associate Professor
Faculty, TEMPE Campus, Mailcode 7301
Biography: 

Nicholas Stephanopoulos is an assistant professor in the School of Molecular Sciences and the Biodesign Institute's Center for Molecular Design and Biomimetics at ASU. He received his undergraduate degree in chemistry from Harvard University in 2004, followed by a master's in chemical engineering from MIT before heading to the University of California, Berkeley for his graduate studies in chemistry. At Berkeley, he studied under Professor Matthew Francis modifying viral capsids for use in nanomaterials, and received his doctorate in 2010. He then moved to Northwestern University as an National Institutes of Health (NIH) postdoctoral fellow with Professor Samuel Stupp, working on self-assembling peptide and peptide-DNA hybrid materials for applications in regenerative medicine. In 2015, he came to ASU, where his interests include the synthesis of novel protein- and peptide-DNA nanomaterials and their application to biology, medicine, energy, and fundamental self-assembly. His work is at the interface of supramolecular chemistry, organic synthesis and bioconjugation, biology, engineering, and nanoscience. Since arriving at ASU, Nick has received several accolades, including the Air Force Young Investigator, NSF CAREER, and NIH New Innovator Awards.

CV
Binary Data Curriculum Vitae
Education: 
  • Ph.D., University of California, Berkeley 2010
  • M.S.C.E.P. Massachusetts Institute of Technology 2007
  • A.B. Chemistry (summa cum laude), Harvard University 2004
Research Website URL: 
https://www.stephanopouloslab.com/
Research Interests: 

Our laboratory is interested in constructing novel nanomaterials from biological molecules such as proteins, peptides, and DNA. In particular, we aim to merge the complex programmability of DNA nanotechnology with the structural and functional diversity of proteins through the synthesis of well-defined protein-DNA hybrids. This research program is by its nature highly interdisciplinary, and lies at the interface of chemistry, nanotechnology, biology, engineering, and medicine. Our work is centered around three main themes:

1) The controlled modification of proteins and peptides at multiple locations with DNA. We are developing methods for the selective conjugation and purification of protein-DNA hybrids in order to control the orientation of proteins on DNA nanostructure scaffolds. This effort merges organic bioconjugation chemistry with protein engineering and peptide synthesis.

2) Construction of complex nanomaterials from proteins and DNA. Although DNA nanotechnology excels at creating complex structures, these materials are limited to the physical and chemical properties of nucleic acids. Biology, on the other hand, uses proteins for a broad range of structural and functional goals. Using protein/peptide-DNA conjugates, we are constructing hybrid nanomaterials for application in targeted drug delivery, protein structural characterization, as well as nanoscale machines and devices.

3) Hierarchical engineering of micro-tissues with single-cell resolution. Natural tissues possess organization across multiple length scales, from nanometers to centimeters and beyond. The ability to control the arrangement of cells along with their complex extracellular matrix will allow for the synthesis of tissues mimicking the complexity of biological structures like the brain. We are developing protein-DNA hybrid biomaterials that will allow us to span these length scales and construct three-dimensional cell aggregates to answer medically and biologically relevant questions in fields like neuroscience, stem cell biology, and embryonic development.

Publications: 

Independent Career (* = corresponding author):

  • N. Stephanopoulos, P. Šulc, "DNA Nanodevices as Mechanical Probes of Protein Structure and Function"  Applied Sciences (2021).
  • S.J.W. Henry, N. Stephanopoulos, "Functionalizing DNA nanostructures for therapeutic applications" WIREs (2021).
  • C.R. Simmons, T. MacCulloch, F. Zhang, Y. Liu, N. Stephanopoulos, H. Yan, "A Self-Assembled Rhombohedral DNA Crystal Scaffold with Tunable Cavity Sizes and High-Resolution Structural Detail" Angewandte Chemie-International Edition (2020).
  • F.M. Fallon, N. Stephanopoulos, J.L. Nicholas, "Reversible control of biomaterial properties for dynamically tuning cell behavior"  Journal of Applied Polymer Science (2020).
  • N. Stephanopoulos, "Hybrid Nanostructures from the Self-Assembly of Proteins and DNA" Chem (2020).
  • A. Buchberger, CR Simmons, NE Fahmi, R Freeman, N. Stephanopoulos, "Hierarchical Assembly of Nucleic Acid/Coiled-Coil Peptide Nanostructures"  Journal of the American Chemical Society (2020).  
  • N. Stephanopoulos, "Peptide-Oligonucleotide Hybrid Molecules for Bioactive Nanomaterials" Bioconjugate Chemistry (2019).
  • N. Stephanopoulos*, “Integrating proteins with DNA nanotechnology” Chem (invited tutorial review, in preparation)
  • N. Stephanopoulos*, “Strategies for stabilizing DNA nanostructures to biological conditions” ChemBioChem (ASAP online: http://dx.doi.org/10.1002/cbic.201900075)
  • N. Stephanopoulos, "Strategies for Stabilizing DNA Nanostructures to Biological Conditions" Chembiochem 2019 (https://doi.org/10.1002/cbic.201900075)
  • Y. Xu, S. Jiang, C. Simmons, R.P. Narayanan, F. Zhang, A.-M. Aziz, H. Yan, N. Stephanopoulos*, “Tunable nanoscale cages from self-assembling DNA and protein building blocks” ACS Nano 2019 (ASAP online: https://pubs.acs.org/doi/full/10.1021/acsnano.8b09798)
  • A. Stelson, M. Liu, C. Little, C. Long, N. Orloff, N. Stephanopoulos*, J. Booth*, “Label-free detection of conformational changes in switchable DNA nanostructures with microwave microfluidics” Nat. Commun. 2019 (ASAP online: https://www.nature.com/articles/s41467-019-09017-z)
  • T. Mahatmanto, I. Azizah, A. Buchberger, N. Stephanopoulos, "Progress toward sourcing plants for new bioconjugation tools: a screening evaluation of a model peptide ligase using a synthetic precursor" 3 Biotech.  2019 https://doi.org/10.1007/s13205-019-1983-2
  • T. MacCulloch, A. Buchberger, N. Stephanopoulos*, “Emerging applications of peptide-oligonucleotide conjugates: bioactive scaffolds, self-assembling systems, and hybrid nanomaterials” Org. Biomol. Chem. 2019, 17, 1668-1682.
  • M. Liu, S. Jiang, O. Loza, N.E. Fahmi, P. Šulc, N. Stephanopoulos*, “Rapid photo-actuation of a DNA nanostructure using an internal photocaged trigger strand” Angew. Chem. Int. Ed. 2018, 57, 9341-9345.
  • N. Stephanopoulos*, R. Freeman*, “DNA-based materials as self-assembling scaffolds for interfacing with cells” (invited book chapter), “Self-Assembling Biomaterials: Molecular Design, Characterization and Application in Biology and Medicine, 1st Edition” 2018, pp. 157-175. (Elsevier)
  • L. Avolio, D. Sipes, N. Stephanopoulos, S. Sur*, “Recreating stem-cell niches using self-assembling biomaterials” (invited book chapter), “Self-Assembling Biomaterials: Molecular Design, Characterization and Application in Biology and Medicine, 1st Edition” 2018, pp. 421-454. (Elsevier)
  • R. Freeman, M. Han, Z. Alvarez, J.A. Lewis, J.R. Wester, N. Stephanopoulos, M.T. McClendon, C. Lynsky, J.M. Godbe, H. Sangji, E. Luijten, S.I. Stupp, "Reversible self-assembly of superstructured networks" 2018 362, 6416, 808-813 (Science)
  • C. Simmons, F. Zhang, T. MacCulloch, N.E. Fahmi, N. Stephanopoulos, Y. Liu, N. Seeman, H. Yan*, “Tuning the Cavity Size and Chirality of Self-Assembling 3D DNA Crystals” J. Am. Chem. Soc. 2017, 139, 11254-11260.
  • D. Varun, G.R. Srinivaan, Y.-H. Tsai, H.-J. Kim, J. Cutts, F. Petty, R. Merkley, N. Stephanopoulos, D. Dolezalova, M. Marsala, D.A. Brafman*, “A Robust Vintronectin-Derived Peptide for the Scalable Long-term Expansion and Neuronal Differentiation of Human Pluripotent Stem Cell (hPSC)-derived Neural Progenitor Cells (hNPCs)” Acta Biomater. 2017, 48, 120-130.

Postdoctoral and Graduate Research (* = co-first author):

  • R. Freeman, M. Han, Z. Álvarez, J.A. Lewis, J.R. Wester, N. Stephanopoulos, M.T. McClendon, C. Lynsky, J.M. Godbe, H. Sangji, E. Luijten, S.I. Stupp, “Reversible self-assembly of superstructured networks” Science 2018, 362, 808-813.
  • J.J. Greene, M.T. McClendon, N. Stephanopoulos, Z. Alvarez, S.I. Stupp, C.-P. Richter, “Electrophysiological Assessment of a Peptide Amphiphile Nanofiber Nerve Graft for Facial Nerve Repair” J. Tissue Eng.  Regen. Med. 2018, 12, 1389–1401.
  • A.J. Matsuoka , Z.A. Sayed, Nicholas Stephanopoulos, E.J. Berns, A.R. Wadhwani, Z.D. Morrissey, D.M. Chadly, S. Kobayashi, A.N. Edelbrock, T. Mashimo, C.A. Miller, T.L. McGuire, S.I. Stupp, J.A. Kessler “Creating a stem cell niche in the inner ear using self-assembling peptide amphiphiles” PLoS ONE 2017, 12, e0190150
  • Ronit Freeman*, Nicholas Stephanopoulos*, Zaida Álvarez, Jacob A. Lewis, Shantanu Sur, Chris M. Serrano, Job Boekhoven, Sungsoo S. Lee, Samuel I. Stupp, “Instructing cells with programmable DNA-peptide hybrids” Nat. Commun. 2017, 8, 15982
  • C. Rubert-Perez, N. Stephanopoulos, S.S. Lee, S. C. Newcomb, Sur, S.I. Stupp, “The Powerful Functions of Peptide-Based Bioactive Matrices for Regenerative Medicine” (invited review) Ann. Biomed. Eng. 2015, 43, 501-514.
  • N. Stephanopoulos, R. Freeman, H.N. Scheler, S. Sur, S. Jeong, F. Tantakitti, J.A. Kessler, S.I. Stupp, “Bioactive DNA-Peptide Nanotubes Enhance the Differentiation of Neural Stem Cells Into Neurons” Nano Lett. 2015, 15, 603-609.
  • A. Li, A. Hokugo, A. Yalom, E.J. Berns, N. Stephanopoulos, M.T. McClendon, L.A. Segovia, I. Spigelman, S.I. Stupp, R. Jarrahy., “A bioengineered peripheral nerve construct using aligned peptide amphiphile nanofibers” Biomaterials 2014, 35, 8780-8790.
  • J. Sack, N. Stephanopoulos, D.C. Austin, M.B. Francis, J.S. Trimmer, “Antibody-guided photoablation of voltage-gated potassium channels” J. Gen. Physiol. 2013, 142, 315-324.
  • N. Stephanopoulos, J.H. Ortony, S.I. Stupp, “Self-Assembly for the Synthesis of Functional Biomaterials” (invited review) Acta Materialia (special Diamond Jubilee Issue), 2013, 61, 912-930.
  • N. Stephanopoulos, M.B. Francis, “Making New Materials from Viral Capsids” (invited book chapter) “Polymer Science: A Comprehensive Reference, 1st Edition” 2012, Vol. 9, pp. 247-266. (Elsevier)
  • N. Stephanopoulos, M.B. Francis, “Choosing an Effective Protein Bioconjugation Strategy.” (invited review) Nat. Chem. Biol. 2011, 7, 876-884.
  • P.G. Holder, D.T. Finley, N. Stephanopoulos, R. Walton, D.S. Clark, M.B. Francis, “Dramatic Thermal Stability of Virus-Polymer Conjugates in Hydrophobic Solvents” Langmuir 2010, 26, 17383–17388.
  • N. Stephanopoulos, G.J. Tong, S.C. Hsiao, M.B. Francis, “Dual-Surface Modified Virus Capsids for Targeted Delivery of Photodynamic Agents to Cancer Cells” ACS Nano, 2010, 4, 6014-6020.
  • N. Stephanopoulos*, M. Liu*, G.J. Tong, Z. Li, Y. Liu, H. Yan, M.B. Francis, “Immobilization and One-Dimensional Arrangement of Virus Capsids with Nanoscale Precision Using DNA Origami” Nano Lett. 2010, 10, 2714-2720.
  • R.A. Miller, N. Stephanopoulos, J.M. McFarland, A.S. Rosko, P.L. Geissler, M.B. Francis, “The Impact of Assembly State on the Defect Tolerance of TMV-based Light Harvesting Arrays” J. Am. Chem. Soc. 2010, 132, 6068-6074.
  • N. Stephanopoulos, Z.M. Carrico, M.B. Francis, “Nanoscale Integration of Sensitizing Chromophores and Porphyrins Using Bacteriophage MS2” Angew. Chem. Int. Ed. 2009, 121, 9662-9666.
  • N. Stephanopoulos, E.O.P. Solis, G. Stephanopoulos, “Nanoscale process systems engineering: Toward molecular factories, synthetic cells, and adaptive devices” (invited perspective) AIChE J. 2005, 51, 1858-1869.
  • A. Stelson, M. Liu, C. Little, C. Long, N. Orloff, N. Stephanopoulos, J. Booth, "Label-free detection of conformational changes in switchable DNA nanostructures with microwave microfluidics" Nature Communications 2019.
  • T. MacCullock, A. Buchberger, N Stephanopoulos, "Emerging applications of peptide-oligonucleotide conjugates: bioactive scaffolds, self-assembling systems, and hybrid nanomaterials" Organic & Biomolecular Chemistry (2019).
  • M. Liu, S. Jiang, O. Loza, N. E. Fahmi, P. Šulc, N. Stephanopoulos, "Rapid photo-actuation of a DNA nanostructure using an internal photocaged trigger strand" Angewandte Chemie 2018, 57, 9341-9345.
Spring 2021
Course NumberCourse Title
CHM 494Special Topics
MBB 495Undergraduate Research
CHM 598Special Topics
Fall 2020
Course NumberCourse Title
CHM 233General Organic Chemistry I
Spring 2020
Course NumberCourse Title
MBB 495Undergraduate Research
CHM 598Special Topics
Summer 2019
Course NumberCourse Title
MBB 495Undergraduate Research
Spring 2019
Course NumberCourse Title
MBB 495Undergraduate Research
CHM 598Special Topics
Fall 2018
Course NumberCourse Title
CHM 233General Organic Chemistry I
Summer 2018
Course NumberCourse Title
MBB 495Undergraduate Research
Spring 2018
Course NumberCourse Title
MBB 495Undergraduate Research
CHM 598Special Topics
Fall 2017
Course NumberCourse Title
CHM 233General Organic Chemistry I
Summer 2017
Course NumberCourse Title
MBB 495Undergraduate Research
Spring 2017
Course NumberCourse Title
MBB 495Undergraduate Research
CHM 598Special Topics
Expertise Areas: 
Biochemistry
Fundamental Molecular Science
Materials Science
Nanoscience
Organic Chemistry