About

Stephen C. Harrison is a Professor of Biological Chemistry and Molecular Pharmacology who has played a central role in guiding Harvard’s Biochemical Sciences Tutorial Program for decades, including serving as Head Tutor from 1972-1996. His contributions emphasize that students should learn how to think about scientific problems and how discoveries emerge from evidence, rather than just absorbing facts. Harrison has been involved in the program's development, which focuses on small-group discussions, close mentorship, and engagement with primary scientific literature, fostering an environment where students develop an intellectual relationship with practicing scientists. His work has helped shape the tutorial’s focus on scientific thinking, evidence interpretation, and mentorship, contributing to Harvard’s undergraduate training in the life sciences.

Research topics

• Neuroscience
• Biology
• Genetics
• Biophysics
• Endocrinology
• Cell biology
• Optometry
• Medicine
• Anatomy
• Biochemistry
• Psychology
• Immunology
• Ophthalmology

Selected publications

• Unsolved retinal questions

  Progress in Retinal and Eye Research · 2026-02-19

  articleOpen access1st authorCorresponding

  The era of modern retinal studies began over 60 years ago when it became possible to record and stain intracellularly individual neurons in each of the five retinal cell classes (MacNichol and Svaetichin, 1958; Tomita et al., 1967; Werblin and Dowling, 1969; Kaneko, 1970). Other technological advances over the past half century have also greatly facilitated research on molecular and cellular mechanisms underlying retinal function and synaptic circuitry. At the anatomical level, cellular mechanisms and classification has advanced with antibody labeling (Ghosh et al., 2004) and the use of genetic markers (Sanes and Masland, 2015). The ultrastructure of retinal synapses and their arrangements has been revealed with electron microscopic analysis (Dowling and Boycott, 1966). and more recently, connectomic methods have been used to study the ultrastructural cellular and synaptic connectivity in a given retinal volume (Marc et al., 2013; Kim et al., 2026). At the physiological level, light responses from all classes of retinal neurons were first recorded with sharp micropipettes, and then with patch clamping techniques (Werblin and Dowling, 1969; Wu et al., 2000). Further, living retinal slices and flat-mounted retinal preparations were developed that allow for the recording of pharmacologically identifiable excitatory and inhibitory currents in single or multiple retinal cells under visual control (Werblin, 1978; Gao et al., 2000; Pang et al., 2024), Finally, the use of mutant animals to uncover aspects of visual function and behavior has come to the fore as well (Emran et al., 2007). Three senior scientists, either retired or close to retirement, whose laboratories participated in a number of these studies review this progress and suggest directions for future investigations.

  PublisherDOI

• High-throughput ultrastructural analysis of macular telangiectasia type 2

  Frontiers in Ophthalmology · 2024-07-30 · 3 citations

  articleOpen accessSenior authorCorresponding

  Introduction: Macular Telangiectasia type 2 (MacTel), is an uncommon form of late-onset, slowly-progressive macular degeneration. Associated with regional Müller glial cell loss in the retina and the amino acid serine synthesized by Müller cells, the disease is functionally confined to a central retinal region - the MacTel zone. Methods: We have used high-throughput multi-resolution electron microscopy techniques, optimized for disease analysis, to study the retinas from two women, mother and daughter, aged 79 and 48 years respectively, suffering from MacTel. Results: In both eyes, the principal observations made were changes specific to mitochondrial structure both outside and within the MacTel zone in all retinal cell types, with the exception of those in the retinal pigment epithelium (RPE). The lesion areas, which are a hallmark of MacTel, extend from Bruch's membrane and the choriocapillaris, through all depths of the retina, and include cells from the RPE, retinal vascular elements, and extensive hypertrophic basement membrane material. Where the Müller glial cells are lost, we have identified a significant population of microglial cells, exclusively within the Henle fiber layer, which appear to ensheathe the Henle fibers, similar to that seen normally by Müller cells. Discussion: Since Müller cells synthesize retinal serine, whereas retinal neurons do not, we propose that serine deficiency, required for normal mitochondrial function, may relate to mitochondrial changes that underlie the development of MacTel. With mitochondrial changes occurring retina-wide, the question remains as to why the Müller cells are uniquely susceptible within the MacTel zone.

  PublisherDOI

• Deferring Puberty in Transgender Adolescents and Associated Clinical Care

  Physician Assistant Clinics · 2024-04-04

  article
  PublisherDOI

• Neuromodulation: Actions of Dopamine, Retinoic Acid, Nitric Oxide, and Other Substances on Retinal Horizontal Cells

  Eye and Brain · 2023-10-01 · 5 citations

  reviewOpen accessSenior author

  Whereas excitation and inhibition of neurons are well understood, it is clear that neuromodulatory influences on neurons and their synapses play a major role in shaping neural activity in the brain. Memory and learning, emotional and other complex behaviors, as well as cognitive disorders have all been related to neuromodulatory mechanisms. A number of neuroactive substances including monoamines such as dopamine and neuropeptides have been shown to act as neuromodulators, but other substances thought to play very different roles in the body and brain act as neuromodulators, such as retinoic acid. We still understand little about how neuromodulatory substances exert their effects, and the present review focuses on how two such substances, dopamine and retinoic acid, exert their effects. The emphasis is on the underlying neuromodulatory mechanisms down to the molecular level that allow the second order bipolar cells and the output neurons of the retina, the ganglion cells, to respond to different environmental (ie lighting) conditions. The modulation described affects a simple circuit in the outer retina, involves several neuroactive substances and is surprisingly complex and not fully understood.

  PublisherOA PDFDOI

• Restoring partial vision to a blind patient

  Faculty Reviews · 2022-06-27

  letterOpen access

  .

  PublisherDOI

• Evaluation of preprocessing techniques for chief complaint classification

  UNC Libraries · 2021-08-19

  articleOpen access1st authorCorresponding

  OBJECTIVE: To determine whether preprocessing chief complaints before automatically classifying them into syndromic categories improves classification performance. METHODS: We preprocessed chief complaints using two preprocessors (CCP and EMT-P) and evaluated whether classification performance increased for a probabilistic classifier (CoCo) or for a keyword-based classifier (modification of the NYC Department of Health and Mental Hygiene chief complaint coder (KC)). RESULTS: CCP exhibited high accuracy (85%) in preprocessing chief complaints but only slightly improved CoCo's classification performance for a few syndromes. EMT-P, which splits chief complaints into multiple problems, substantially increased CoCo's sensitivity for all syndromes. Preprocessing with CCP or EMT-P only improved KC's sensitivity for the Constitutional syndrome. CONCLUSION: Evaluation of preprocessing systems should not be limited to accuracy of the preprocessor but should include the effect of preprocessing on syndromic classification. Splitting chief complaints into multiple problems before classification is important for CoCo, but other preprocessing steps only slightly improved classification performance for CoCo and a keyword-based classifier.

  PublisherDOI

• A connectomics approach to understanding a retinal disease

  Proceedings of the National Academy of Sciences · 2020-07-22 · 22 citations

  articleOpen accessSenior authorCorresponding

  Macular telangiectasia type 2 (MacTel), a late-onset macular degeneration, has been linked to a loss in the retina of Müller glial cells and the amino acid serine, synthesized by the Müller cells. The disease is confined mainly to a central retinal region called the MacTel zone. We have used electron microscopic connectomics techniques, optimized for disease analysis, to study the retina from a 48-y-old woman suffering from MacTel. The major observations made were specific changes in mitochondrial structure within and outside the MacTel zone that were present in all retinal cell types. We also identified an abrupt boundary of the MacTel zone that coincides with the loss of Müller cells and macular pigment. Since Müller cells synthesize retinal serine, we propose that a deficiency of serine, required for mitochondrial maintenance, causes mitochondrial changes that underlie MacTel development.

  PublisherOA PDFDOI

• Restoring vision to the blind

  Science · 2020 · 20 citations

  1st authorCorresponding
  • Optometry
  • Medicine
  • Psychology

  Ideas abound to restore vision to people blinded by retinal disease

  PublisherDOI

• Connectomic reconstruction of the human midget pathway: unexpected connectivity linked to preterm birth

  Investigative Ophthalmology & Visual Science · 2020-06-10 · 1 citations

  articleOpen access
  Publisher

• Rods Contribute to Visual Behavior in Larval Zebrafish

  Investigative Ophthalmology & Visual Science · 2020 · 29 citations

  • Biology
  • Anatomy
  • Biophysics

  Purpose: Although zebrafish rods begin to develop as early as 2 days postfertilization (dpf), they are not deemed anatomically mature and functional until 15 to 21 dpf. A recent study detected a small electroretinogram (ERG) from rods in a cone mutant called no optokinetic response f (nof) at 5 dpf, suggesting that young rods are functional. Whether they can mediate behavioral responses in larvae is unknown. Methods: We first confirmed rod function by measuring nof ERGs under photopic and scotopic illumination at 6 dpf. We evaluated the role of rods in visual behaviors using two different assays: the visual-motor response (VMR) and optokinetic response (OKR). We measured responses from wild-type (WT) larvae and nof mutants under photopic and scotopic illuminations at 6 dpf. Results: Nof mutants lacked a photopic ERG. However, after prolonged dark adaptation, they displayed scotopic ERGs. Compared with WT larvae, the nof mutants displayed reduced VMRs. The VMR difference during light onset gradually diminished with decreased illumination and became nearly identical at lower light intensities. Additionally, light-adapted nof mutants did not display an OKR, whereas dark-adapted nof mutants displayed scotopic OKRs. Conclusions: Because the nof mutants lacked a photopic ERG but displayed scotopic ERGs after dark adaptation, the mutants clearly had functional rods. WT larvae and the nof mutants displayed comparable scotopic light-On VMRs and scotopic OKRs after dark adaptation, suggesting that these responses were driven primarily by rods. Together, these observations indicate that rods contribute to zebrafish visual behaviors as early as 6 dpf.

  PublisherOA PDFDOI

Recent grants

• NIH Grant R01EY015163

  NIH · $1.9M · 2011

• Ultrastructural Analysis of a Form of Macular Degeneration - Macular Telangiectasia

  NIH · $561k · 2020–2023

• NIH Grant R01EY000824

  NIH · $3.5M · 2003

• NIH Grant R01EY000811

  NIH · $6.9M · 2012

• NIH Grant R37EY000811

  NIH · $2.5M · 1996

Frequent coauthors

• Harris Ripps

  University of Illinois Chicago

  85 shared

• Richard L. Chappell

  Marine Biological Laboratory

  46 shared

• Haohua Qian

  National Institutes of Health

  19 shared

• Alan R. Adolph

  Harvard University

  18 shared

• Farida Emran

  McGill University Health Centre

  15 shared

• Yuk Fai Leung

  Purdue University West Lafayette

  15 shared

• Ellen A. Schmitt

  Harvard University

  14 shared

• Keith J. Watling

  Griffith University

  12 shared

Labs

• Harvard’s Biochemical Sciences Tutorial ProgramPI