About

Stephen C. Harrison is a Professor of Biological Chemistry and Molecular Pharmacology at Harvard University who has played a central role in guiding the Biochemical Sciences Tutorial Program for decades. He served as Head Tutor of the program from 1972 to 1996, contributing significantly to its development and enduring legacy. Harrison emphasizes that the tutorial program was designed not merely for students to absorb biological facts but to learn how to think critically about scientific problems and understand how discoveries emerge from evidence. Under his guidance, the program fostered intellectual relationships between students and practicing scientists, encouraging students to read and discuss primary research papers, analyze experiments, and interpret scientific evidence. Harrison highlights that tutors also serve as primary academic advisors, mentoring students throughout their undergraduate concentration and helping them pursue laboratory research and senior honors thesis projects. He notes that one advantage of the tutorial system was its ability to recruit faculty working in emerging scientific fields, thereby exposing undergraduates to new areas of science before they became standard parts of the curriculum. Through his leadership, the Biochemical Sciences Tutorial Program has remained a defining feature of Harvard's life sciences education, shaping generations of students by cultivating curiosity, critical thinking, and scientific conversation.

Research topics

• Biology
• Biochemistry
• Biophysics
• Chemistry
• Cell biology
• Crystallography
• Immunology
• Nanotechnology
• Evolutionary biology
• Virology
• Materials science

Selected publications

• Fluorescence-barcoded cell lines stably expressing membrane-anchored influenza neuraminidases

  Vaccine · 2025-04-21

  articleOpen access

  The discovery of broadly protective antibodies to the influenza virus neuraminidase (NA) has raised interest in NA as a vaccine target. However, recombinant, solubilized tetrameric NA ectodomains are often challenging to express and isolate, hindering the study of anti-NA humoral responses. To address this obstacle, we established a panel of 22 non-adherent cell lines stably expressing native, historical N1, N2, N3, N9, and NB NAs anchored on the cell surface. The cell lines are barcoded with fluorescent proteins, enabling high-throughput, 16-plex analyses of antibody binding with commonly available flow cytometers. The cell lines were at least as efficient as a Luminex multiplex binding assay at identifying NA antibodies from a library of unselected clonal IgGs derived from human memory B cells. The cell lines were also useful for measuring the magnitude and breadth of the serum antibody response elicited by experimental infection of rhesus macaques with influenza virus. The membrane-anchored NAs are catalytically active and are compatible with established sialidase activity assays. NA-expressing K530 cell lines therefore represent a useful tool for studying NA immunity and evaluating influenza vaccine efficacy.

  PublisherDOI

• Structures of folding intermediates on BAM show diverse substrates fold by a uniform mechanism

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-10-17 · 1 citations

  preprintOpen access

  The outer membranes of mitochondria, chloroplasts, and Gram-negative bacteria contain β-barrel membrane proteins that are assembled by conserved multi-subunit machines. In bacteria, the β-barrel assembly machine (BAM) folds over a hundred compositionally different substrates into barrels that vary greatly in size. Some larger barrels require globular proteins to plug the barrel lumen. How a single machine can assemble such different barrels is unknown. Here we report three structures representing progressively folded stages of a 16-stranded barrel engaged with BAM, as well as the structure of a late-stage folding intermediate of a 26-stranded substrate folding around its soluble lipoprotein plug on BAM. We find that BAM catalyzes folding of these substrates by a uniform mechanism in which BAM undergoes major distortions to accommodate the nascent barrel.

  PublisherOA PDFDOI

• Fluorescence-barcoded cell lines stably expressing membrane-anchored influenza neuraminidases

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-01-02

  preprintOpen access

  The discovery of broadly protective antibodies to the influenza virus neuraminidase (NA) has raised interest in NA as a vaccine target. However, recombinant, solubilized tetrameric NA ectodomains are often challenging to express and isolate, hindering the study of anti-NA humoral responses. To address this obstacle, we established a panel of 22 non-adherent cell lines stably expressing native, historical N1, N2, N3, N9, and NB NAs anchored on the cell surface. The cell lines are barcoded with fluorescent proteins, enabling high-throughput, 16-plex analyses of antibody binding with commonly available flow cytometers. The cell lines were at least as efficient as a Luminex multiplex binding assay at identifying NA antibodies from a library of unselected clonal IgGs derived from human memory B cells. The cell lines were also useful for measuring the magnitude and breadth of the serum antibody response elicited by experimental infection of rhesus macaques with influenza virus. The membrane-anchored NAs are catalytically active and are compatible with established sialidase activity assays. NA-expressing K530 cell lines therefore represent a useful tool for studying NA immunity and evaluating influenza vaccine efficacy.

  PublisherOA PDFDOI

• A coordinated kinase and phosphatase network regulates Stu2 recruitment to yeast kinetochores

  The Journal of Cell Biology · 2025-05-23 · 1 citations

  articleOpen access

  Cells coordinate diverse events at anaphase onset, including separase activation, cohesin cleavage, chromosome separation, and spindle reorganization. Regulation of the XMAP215 family member and microtubule polymerase, Stu2, at the metaphase-anaphase transition determines a redistribution from kinetochores to spindle microtubules. We show that cells modulate Stu2 kinetochore-microtubule localization by Polo-like kinase1/Cdc5-mediated phosphorylation of T866, near the Stu2 C-terminus, thereby promoting dissociation from the kinetochore Ndc80 complex. Cdk/Cdc28 likely primes Cdc5:Stu2 interaction. Cdc28 activity is also required for Stu2 nuclear import. PP2ACdc55 actively opposes Cdc5 activity on Stu2T866 during metaphase. This counter-regulation allows for switch-like redistribution of Stu2pT866 at anaphase onset when separase inhibits PP2ACdc55. Blocking Stu2T866 phosphorylation disrupts anaphase spindle progression, and we infer that PP2ACdc55 regulates the mitotic spindle by dephosphorylating multiple MAPs, including Stu2. These data support a model in which increased phosphorylation at anaphase onset results from phosphatase inhibition and point to a larger regulatory network that facilitates rapid cytoskeletal modulation required for anaphase spindle function.

  PublisherOA PDFDOI

• Performance Comparison of a Transpired Air Solar Collector with Low-E Surface Coating

  2024-01-01

  article
  PublisherDOI

• A coordinated kinase and phosphatase network regulates Stu2 recruitment to yeast kinetochores

  bioRxiv (Cold Spring Harbor Laboratory) · 2024-11-03 · 1 citations

  preprintOpen access

  ABSTRACT Cells coordinate diverse events at anaphase onset, including separase activation, cohesin cleavage, chromosome separation, and spindle reorganization. Regulation of the XMAP215 family member and microtubule polymerase, Stu2, at the metaphase-anaphase transition determines a specific redistribution from kinetochores to spindle microtubules. We show that cells modulate Stu2 kinetochore-microtubule localization by Polo-like kinase1/Cdc5-mediated phosphorylation of T866, near the Stu2 C-terminus, thereby promoting dissociation from the kinetochore Ndc80 complex. Cdk/Cdc28 likely primes Cdc5:Stu2 interaction. Cdc28 activity is also required for Stu2 nuclear import. PP2A Cdc55 actively opposes Cdc5 activity on Stu2 T866 during metaphase. This counter-regulation allows for switchlike redistribution of Stu2 pT866 at anaphase onset when separase inhibits PP2A Cdc55 . Blocking Stu2 T866 phosphorylation disrupts anaphase spindle progression, and we infer that PP2A Cdc55 regulates the mitotic spindle by dephosphorylating Stu2 and other MAPs. These data support a model in which increased phosphorylation at anaphase onset results from phosphatase inhibition and point to a larger regulatory network that facilitates rapid cytoskeletal modulation required for anaphase spindle maintenance. SUMMARY Stu2 displays dynamic localization patterns in the cell cycle, with different kinetochore and microtubule distribution during distinct phases. Phosphorylation near Stu2’s C-terminus reduces its attachment to kinetochores to promote its microtubule activity in anaphase. Cdc5 and PP2A Cdc55 play counteracting roles in this pathway to promote proper timing of Stu2 phosphorylation.

  PublisherOA PDFDOI

• Vertical Juxtaposition in Horace Odes 1

  2024-02-19

  book-chapterOpen access1st authorCorresponding

  The elaborate and effective combination of word-order, metre, and sound-effect is one of the key features of Horace's Odes. This piece presents an initial consideration of the under-investigated phenomenon of vertical juxtaposition of related words in consecutive lyric lines. The ways in which these vertically juxtaposed words are linked are various, from simple anaphora and rhyme to the pairing of words which relate to each other in shape, sense, grammar or sound. These connections form interlocking structural and euphonic patterns which contribute materially to the poetic texture of the Odes.

  PublisherOA PDFDOI

• Oxford Classical Reception Commentaries and Their Aims

  2024-05-07

  other
  PublisherDOI

• Horace on Sacred Space

  Cambridge University Press eBooks · 2024-06-14

  book-chapter1st authorCorresponding
  PublisherDOI

• Octahedral small virus-like particles of dengue virus type 2

  bioRxiv (Cold Spring Harbor Laboratory) · 2024-10-18

  preprintOpen accessSenior authorCorresponding

  ABSTRACT Flavivirus envelope (E) and precursor M (prM) proteins, when ectopically expressed, assemble into empty, virus-like particles (VLPs). Cleavage of prM to M and loss of the pr fragment converts the VLPs from immature to mature particles, mimicking a similar maturation of authentic virions. Most of the VLPs obtained by prM-E expression are smaller than virions; early, low-resolution cryo-EM studies suggested a simple, 60-subunit, icosahedral organization. We describe here the cryo-EM structure of immature, small VLPs from dengue virus type 2 and show that they have octahedral rather than icosahedral symmetry. The asymmetric unit of the octahedral particle is an asymmetric trimer of prM-E heterodimers, just as it is on icosahedral immature virions; the full, octahedrally symmetric particle thus has 24 such asymmetric trimers, or 72 prM-E heterodimers in all. Cleavage of prM and release of pr generates ovoid, somewhat irregular, mature particles. Previous work has shown that mature smVLPs have fusion properties identical to those of virions, consistent with local, virion-like clustering of 36 E dimers on their surface. The cryo-EM structure and the properties of these VLPs described here relate directly to on-going efforts to use them as vaccine immunogens. IMPORTANCE Ectopic expression of flavivirus envelope (E) and precursor M (prM) proteins leads to formation and secretion of empty, virus-like particles (VLPs), which are candidate, non-infectious, virion-like components of flavivirus vaccines. We show that the immature particles of a major class of VLPs -- “small VLPs” (smVLPs), which have smaller diameter than those of virion size, -- are octahedrally (rather than icosahedrally) symmetric, with the same clustering of prM and E, as asymmetric trimers of prM-E heterodimers, found on immature virions. Cleavage of prM and formation of mature, smVLPs yields somewhat irregular, ovoid particles. Design and characterization of VLPs as vaccine components will need to take these properties into account.

  PublisherOA PDFDOI

Recent grants

• NIH Grant P01AI043649

  NIH · $16.4M · 2010

• Structure-function studies of the membrane-interacting domains of HIV-1 Env spike

  NIH · $8.4M · 2016–2026

• Core A: Administrative Core

  NIH · $74.1M · 2011–2028

• NIH Grant R01AI030361

  NIH · $900k · 1996

• NIH Grant R01AI013654

  NIH · $3.3M · 2005

Frequent coauthors

• Aaron G. Schmidt

  Harvard University

  109 shared

• Nikolaus Grigorieff

  Howard Hughes Medical Institute

  100 shared

• Tomas Kirchhausen

  Boston Children's Hospital

  66 shared

• Bing Chen

  Cotton Research Institute

  66 shared

• Simon Jenni

  Harvard University

  60 shared

• Ian W. Windsor

  Pfizer (United States)

  57 shared

• M. Anthony Moody

  Duke University

  56 shared

• Thomas B. Kepler

  55 shared

Labs

• Harvard’s Biochemical Sciences Tutorial ProgramPI