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William M. Shih

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William M. Shih
Born
🎓 Alma materHarvard University (AB)
Stanford University (PhD)
💼 Occupation
Known forDNA origami, Crisscross polymerization, DNA nanoswitch calipers
🏅 AwardsNIH Director's New Innovator Award
Foresight Institute Prize in Experimental Nanotechnology
Rozenberg Tulip Award

William M. Shih is an American biochemist and professor specializing in structural DNA nanotechnology. He is a Professor in the Department of Biological Chemistry and Molecular Pharmacology at Harvard Medical School and the Department of Cancer Biology at the Dana–Farber Cancer Institute. He also serves as a Founding Core Faculty member at the Wyss Institute for Biologically Inspired Engineering at Harvard University.[1]

Shih's research focuses on the development of DNA nanotechnology, with particular emphasis on the design of three-dimensional DNA origami structures.[2]

Education and early career

Shih attended Harvard University, where he earned his Bachelor of Arts in Biochemical Sciences. He completed his doctoral studies at Stanford University, receiving a Ph.D. in Biochemistry.

He performed his postdoctoral fellowship at The Scripps Research Institute under the supervision of Gerald Joyce. During this period, he notably demonstrated that a 1.7-kilobase-pair single strand of DNA could be folded into a nanoscale octahedron, a significant milestone in programmed molecular self-assembly.[3]

Research

Shih's research laboratory focuses on the design principles for self-assembling molecular machines using structural DNA nanotechnology. His work bridges the gap between synthetic nanostructures and biological systems to address problems of biological and medical interest.

DNA-based architectures

To overcome the scalability limits of traditional DNA origami, Shih's group developed crisscross polymerization. This strategy combines the absolute scaffold-dependence of DNA origami with the unbounded size potential of DNA tile assembly, enabling the construction of microscale structures with precise control over copy number.[4]

Single-molecule and structural analysis

In collaboration with Wesley Wong, Shih developed DNA nanoswitch calipers for massively parallel single-molecule identification and mechanical characterization. This technology aims to advance single-cell proteomics by enabling high-throughput determination of protein structures.[5]

Additionally, Shih pioneered the use of DNA nanotubes as an alignment medium to enable NMR structure determination of membrane proteins.[6]

Therapeutic vehicles

Shih explores the use of DNA-origami pegboards to present precise spatial arrangements of ligands, such as CpG oligonucleotides. In collaboration with groups at KIST and the Dana-Farber Cancer Institute, this research focuses on the immune polarization of dendritic cells to enhance cancer vaccines.[7]

Awards and honors

Selected publications

  • Douglas, S. M.; Dietz, H.; Liedl, T.; Högberg, B.; Graf, F.; Shih, W. M. (2009). "Self-assembly of DNA into nanoscale three-dimensional shapes". Nature. 459 (7245): 414–418. doi:10.1038/nature08016.
  • Dietz, H.; Douglas, S. M.; Shih, W. M. (2009). "Folding DNA into twisted and curved nanoscale shapes". Science. 325 (5941): 725–730. doi:10.1126/science.1174251.

References

  1. "William Shih". Harvard Medical School. Retrieved 2026-02-02.
  2. "William Shih, Ph.D." Wyss Institute at Harvard University. Retrieved 2026-02-02.
  3. Shih, W. M.; Quispe, J. D.; Joyce, G. F. (2004). "A 1.7-kilobase-pair DNA strand folds into a nanoscale octahedron". Nature. 427 (6975): 618–621. doi:10.1038/nature02307.
  4. Minev, D.; Guerra, R.; Shih, W. M. (2021). "Low-error self-assembly of DNA crystals with multi-micrometre dimensions". Nature. 592 (7854): 380–385. doi:10.1038/s41586-021-03414-0.
  5. Halvorsen, K.; Shih, W. M.; Wong, W. P. (2011). "Binary-code wrapping of a genetic cassette into a nanostructure". Nature Methods. 8 (11): 941–943. doi:10.1038/nmeth.1733.
  6. Douglas, S. M.; Chou, J. J.; Shih, W. M. (2007). "DNA-nanotube-induced alignment of membrane proteins for NMR structure determination". Science. 316 (5832): 1709–1712. doi:10.1126/science.1143757.
  7. Liu, S.; Jiang, Q.; Shih, W. M.; Ding, B. (2018). "A DNA nanodevice as a cancer therapeutic". Nature Materials. 17 (4): 312–319. doi:10.1038/s41563-018-0025-z.
  8. "Funded Research — SHIH, WILLIAM M". NIH Common Fund. National Institutes of Health.
  9. "William Shih: 2013 Blavatnik National Awards Finalist". Blavatnik Awards. Retrieved 2026-02-02.
  10. "William Shih wins Foresight Institute Prize". Foresight Institute. Retrieved 2026-02-02.
  11. "The Rozenberg Tulip Award in DNA Computing". ISNSCE. Retrieved 2026-02-02.

External links



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