Nicholas Stephanopoulos

Assistant 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. 

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 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

  • 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
  • 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 Biomaterialia. 2017, 48, 120-130
  • 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” Journal of the American Chemical Society. 2017, 139, 11254-11260
  • Ro. Freeman*, N. Stephanopoulos*, Z. Alvarez, J.A. Lewis, S. Sur, C.M. Serrano, J. Boekhoven, S.S. Lee, S.I. Stupp, “Instructing cells with programmable peptide DNA hybrids” Nature Communications. 2017, 8, 15982
  • 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
  • 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” Annals of Biomedical Engineering. 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
  • 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. (* co-first authors)
  • 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

Courses

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
Fall 2016
Course NumberCourse Title
CHM 233General Organic Chemistry I
Fall 2015
Course NumberCourse Title
CHM 598Special Topics