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, including serving as Head Tutor from 1972 to 1996. He contributed significantly to the program's mission of teaching students not just to absorb biological facts but to learn how to think about scientific problems and understand how discoveries emerge from evidence. Harrison emphasized the importance of students developing intellectual relationships with practicing scientists through reading and discussing primary research papers, fostering critical thinking and scientific reasoning. His leadership helped shape the tutorial into a vital component of Harvard's undergraduate life sciences education, supporting students in Molecular and Cellular Biology and Chemical and Physical Biology concentrations through mentorship and engagement with original scientific literature.

Research topics

• Neuroscience
• Biology
• Cell biology
• Endocrinology
• Medicine
• Internal medicine
• Genetics
• Ecology
• Anatomy
• Psychology
• Immunology
• Biochemistry
• Anesthesia

Selected publications

• Vagal blood volume receptors compensate for haemorrhage and posture change

  Nature · 2026-01-28 · 6 citations

  articleOpen accessSenior author

  Abstract Cranial nerves densely innervate the heart and vasculature, with sensory neurons reporting on blood pressure, respiratory gases and tissue damage 1 . The roles of arterial baroreceptors in systemic physiology are well appreciated 2 , but the functions of vagal cardiac mechanoreceptors have been more difficult to parse, in part due to the closed-loop structure of the cardiovascular system. Here we use genetic tools in mice to identify a small group of neurons that are acutely sensitive to circulating blood volume and initiate a reflex that compensates for decreased filling of the heart in an upright posture and haemorrhage. Vagal PIEZO2 neurons form characteristic end-net endings in the heart, lower blood pressure in response to optogenetic stimulation and display blood-volume-dependent responses with every heartbeat that are time-locked to atrial and ventricular systole. Knockout of Piezo2 and/or ablation of PIEZO2 neurons in vagal ganglia eliminates this heartbeat-coupled nerve activity, causes orthostatic hypotension and compromises cardiovascular stability during trauma-induced blood loss. Together, these findings demonstrate that vagal mechanoreceptors monitor the cardiac cycle and initiate a blood-volume-dependent reflex that defends the constancy of circulation.

  PublisherDOI

• Enteric sensory neurons for nutrient detection and gut motility

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-03-07

  article

  Summary The enteric nervous system (ENS) orchestrates gastrointestinal reflexes and brain-gut communication via molecularly diverse neurons. Among these, intrinsic primary afferent neurons (IPANs) are essential for detecting luminal nutrients and irritants, yet their molecular identities, sensory properties, and functions remain poorly resolved. Here, we establish a segment-resolved single-cell atlas of the murine ENS, including a comprehensive characterization of the gastric ENS. This resource defines a refined taxonomy of enteric neurons and glia and enabled the development of a genetic toolkit for molecularly defined IPANs. Using chemogenetics and calcium imaging, we discovered that myenteric neurons detect a wide range of nutrients, irritants, and cytokines. Nutrient detection depends on a functional connection between chemosensory epithelial cells and enteric neurons mediated by 5-HT—HTR3 axis. Through optogenetic analysis, we demonstrated segment-specific regulation of gut motility by different IPANs. Our work establishes a genetic and physiological framework for enteric-specific sensory mechanisms.

  PublisherDOI

• Vagal volume receptors in the heart compensate for blood loss and posture change

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-12-05

  articleOpen accessSenior authorCorresponding

  Cranial nerves densely innervate the heart and vasculature, with sensory neurons reporting on blood pressure, respiratory gases, and tissue damage 1 . The roles of arterial baroreceptors in systemic physiology are well appreciated 2 , but the functions of vagal cardiac mechanoreceptors have been more difficult to parse, in part due to the closed-loop structure of the cardiovascular system. Here, we use genetic tools for isolated study of vagal mechanoreceptors in the heart, finding that they are acutely sensitive to circulating blood volume and play key roles in compensating for decreased filling of the heart that occurs in an upright posture and during hemorrhage. Vagal PIEZO2 neurons form characteristic end-net endings in the heart and display blood volume-dependent responses with every heartbeat that are timelocked to atrial and ventricular systole. Vagal PIEZO2 knockout eliminates heartbeatcoupled nerve activity, and compromises carotid blood pressure when mice on a tilttable are rotated to an upright position. Vagal PIEZO2 knockout mice also display a lethal failure to sustain blood pressure during trauma-induced blood loss. Together, these findings demonstrate an essential function for vagal cardiac mechanoreceptors in sustaining the constancy of blood circulation.

  PublisherDOI

• Interoception 2025

  Current Opinion in Neurobiology · 2025-10-01

  editorialSenior author
  PublisherDOI

• Sensory Neurons that Detect Stretch and Nutrients in the Digestive System

  Cell · 2025-06-01 · 3 citations

  erratumOpen accessSenior author
  PublisherOA PDFDOI

• Vagal TRPV1 ⁺ sensory neurons protect against influenza virus infection by regulating lung myeloid cell dynamics

  Science Immunology · 2025-08-01 · 8 citations

  article

  Influenza viruses are a major global cause of morbidity and mortality. Although vagal TRPV1 + nociceptive sensory neurons are known to mediate defenses against harmful agents, including pathogens, their function in lung antiviral defenses remains unclear. Our study demonstrates that both systemic and vagal-specific ablation of TRPV1 + nociceptors reduce survival in mice infected with influenza A virus (IAV). Despite no difference in viral load, mice lacking TRPV1 + neurons exhibited increased viral spread, exacerbated lung pathology, and elevated levels of proinflammatory cytokines. Loss of TRPV1 + neurons altered the lung immune landscape, including an expansion of neutrophils and monocyte-derived macrophages. Transcriptional analysis revealed impaired interferon signaling in myeloid cells and an imbalance in distinct neutrophil subpopulations in the absence of nociceptors. Furthermore, antibody-mediated depletion of myeloid cells during IAV infection substantially improved survival after nociceptor ablation, underscoring the role of TRPV1 + neurons in preventing pathogenic myeloid cell states that contribute to IAV-induced mortality.

  PublisherDOI

• Stimulating intestinal GIP release reduces food intake and body weight in mice

  Molecular Metabolism · 2024-04-21 · 23 citations

  articleOpen access

  OBJECTIVE: Glucose dependent insulinotropic polypeptide (GIP) is well established as an incretin hormone, boosting glucose-dependent insulin secretion. However, whilst anorectic actions of its sister-incretin glucagon-like peptide-1 (GLP-1) are well established, a physiological role for GIP in appetite regulation is controversial, despite the superior weight loss seen in preclinical models and humans with GLP-1/GIP dual receptor agonists compared with GLP-1R agonism alone. METHODS: We generated a mouse model in which GIP expressing K-cells can be activated through hM3Dq Designer Receptor Activated by Designer Drugs (DREADD, GIP-Dq) to explore physiological actions of intestinally-released GIP. RESULTS: In lean mice, Dq-stimulation of GIP expressing cells increased plasma GIP to levels similar to those found postprandially. The increase in GIP was associated with improved glucose tolerance, as expected, but also triggered an unexpected robust inhibition of food intake. Validating that this represented a response to intestinally-released GIP, the suppression of food intake was prevented by injecting mice peripherally or centrally with antagonistic GIPR-antibodies, and was reproduced in an intersectional model utilising Gip-Cre/Villin-Flp to limit Dq transgene expression to K-cells in the intestinal epithelium. The effects of GIP cell activation were maintained in diet induced obese mice, in which chronic K-cell activation reduced food intake and attenuated body weight gain. CONCLUSIONS: These studies establish a physiological gut-brain GIP-axis regulating food intake in mice, adding to the multi-faceted metabolic effects of GIP which need to be taken into account when developing GIPR-targeted therapies for obesity and diabetes.

  PublisherDOI

• A vagal reflex evoked by airway closure

  Nature · 2024-03-06 · 41 citations

  articleOpen accessSenior author

  Abstract Airway integrity must be continuously maintained throughout life. Sensory neurons guard against airway obstruction and, on a moment-by-moment basis, enact vital reflexes to maintain respiratory function 1,2 . Decreased lung capacity is common and life-threatening across many respiratory diseases, and lung collapse can be acutely evoked by chest wall trauma, pneumothorax or airway compression. Here we characterize a neuronal reflex of the vagus nerve evoked by airway closure that leads to gasping. In vivo vagal ganglion imaging revealed dedicated sensory neurons that detect airway compression but not airway stretch. Vagal neurons expressing PVALB mediate airway closure responses and innervate clusters of lung epithelial cells called neuroepithelial bodies (NEBs). Stimulating NEBs or vagal PVALB neurons evoked gasping in the absence of airway threats, whereas ablating NEBs or vagal PVALB neurons eliminated gasping in response to airway closure. Single-cell RNA sequencing revealed that NEBs uniformly express the mechanoreceptor PIEZO2, and targeted knockout of Piezo2 in NEBs eliminated responses to airway closure. NEBs were dispensable for the Hering–Breuer inspiratory reflex, which indicated that discrete terminal structures detect airway closure and inflation. Similar to the involvement of Merkel cells in touch sensation 3,4 , NEBs are PIEZO2-expressing epithelial cells and, moreover, are crucial for an aspect of lung mechanosensation. These findings expand our understanding of neuronal diversity in the airways and reveal a dedicated vagal pathway that detects airway closure to help preserve respiratory function.

  PublisherOA PDFDOI

• Brain-body physiology: Local, reflex, and central communication

  Cell · 2024-10-01 · 55 citations

  reviewOpen access
  PublisherOA PDFDOI

• A revised conceptual framework for mouse vomeronasal pumping and stimulus sampling

  Current Biology · 2024-02-05 · 20 citations

  articleOpen access

  The physiological performance of any sensory organ is determined by its anatomy and physical properties. Consequently, complex sensory structures with elaborate features have evolved to optimize stimulus detection. Understanding these structures and their physical nature forms the basis for mechanistic insights into sensory function. Despite its crucial role as a sensor for pheromones and other behaviorally instructive chemical cues, the vomeronasal organ (VNO) remains a poorly characterized mammalian sensory structure. Fundamental principles of its physico-mechanical function, including basic aspects of stimulus sampling, remain poorly explored. Here, we revisit the classical vasomotor pump hypothesis of vomeronasal stimulus uptake. Using advanced anatomical, histological, and physiological methods, we demonstrate that large parts of the lateral mouse VNO are composed of smooth muscle. Vomeronasal smooth muscle tissue comprises two subsets of fibers with distinct topography, structure, excitation-contraction coupling, and, ultimately, contractile properties. Specifically, contractions of a large population of noradrenaline-sensitive cells mediate both transverse and longitudinal lumen expansion, whereas cholinergic stimulation targets an adluminal group of smooth muscle fibers. The latter run parallel to the VNO's rostro-caudal axis and are ideally situated to mediate antagonistic longitudinal constriction of the lumen. This newly discovered arrangement implies a novel mode of function. Single-cell transcriptomics and pharmacological profiling reveal the receptor subtypes involved. Finally, 2D/3D tomography provides non-invasive insight into the intact VNO's anatomy and mechanics, enables measurement of luminal fluid volume, and allows an assessment of relative volume change upon noradrenergic stimulation. Together, we propose a revised conceptual framework for mouse vomeronasal pumping and, thus, stimulus sampling.

  PublisherOA PDFDOI

Recent grants

• Sensory biology of respiratory control neurons in the vagus nerve

  NIH · $1.7M · 2016–2021

• Comprehensive Structural and Functional Mapping of the Mammalian Cardiac Nervous System

  NIH · $21.4M · 2016–2023

• NIH Grant R01DC010155

  NIH · $2.0M · 2014

• Charting Vagal Circuits Containing Glucagon-Like Peptide 1 Receptor

  NIH · $1.5M · 2016–2020

• Sensory receptors of the vagus nerve

  NIH · $5.9M · 2016–2022

Frequent coauthors

• Soohong Min

  Harvard University

  24 shared

• Sara L. Prescott

  Massachusetts Institute of Technology

  22 shared

• Qian Li

  Soochow University

  21 shared

• Judith A. Kaye

  17 shared

• Narendra R. Joshi

  Howard Hughes Medical Institute

  16 shared

• Frank Reimann

  University of Cambridge

  16 shared

• Fiona M. Gribble

  University of Cambridge

  16 shared

• David E. Strochlic

  Howard Hughes Medical Institute

  16 shared

Labs

• Harvard's Biochemical Sciences Tutorial ProgramPI

Education

• PhD, Chemistry and Chemical Biology

  Harvard University

  1999

• BA, Chemistry

  Harvard University

  1994