About

Carolyn Bertozzi is the Baker Family Director of Stanford ChEM-H, Anne T. and Robert M. Bass Professor in the School of Humanities and Sciences, and a Professor, by courtesy, of Chemical and Systems Biology and of Radiology at Stanford University. She completed her undergraduate degree in Chemistry from Harvard University in 1988 and her Ph.D. in Chemistry from UC Berkeley in 1993. After her postdoctoral work at UCSF in cellular immunology, she joined the UC Berkeley faculty in 1996. In June 2015, she joined Stanford University faculty and became the co-director and Institute Scholar at Sarafan ChEM-H. Her research interests span chemistry and biology, with a focus on cell surface glycosylation related to disease states. Her lab studies changes in cell surface glycosylation associated with cancer, inflammation, and bacterial infection, aiming to develop diagnostic and therapeutic approaches, especially in immuno-oncology. She has received numerous honors and awards for her research and teaching, including membership in the National Academy of Sciences, the American Academy of Arts and Sciences, and the German Academy of Sciences Leopoldina, as well as awards such as the Nobel Prize in Chemistry, MacArthur Fellowship, and others.

Research topics

• Biology
• Cell biology
• Biochemistry
• Immunology
• Genetics
• Computational biology
• Chemistry
• Medicine
• Internal medicine
• Cancer research
• Neuroscience
• Psychiatry
• Chromatography
• Microbiology
• Pathology
• Virology
• Psychology
• Organic chemistry

Selected publications

• Ageing promotes microglial accumulation of slow-degrading synaptic proteins

  Nature · 2026-01-21 · 7 citations

  articleOpen access

  Neurodegenerative diseases affect 1 in 12 people globally and remain incurable. Central to their pathogenesis is a loss of neuronal protein maintenance and the accumulation of protein aggregates with ageing1,2. Here we engineered bioorthogonal tools3 that enabled us to tag the nascent neuronal proteome and study its turnover with ageing, its propensity to aggregate and its interaction with microglia. We show that neuronal protein half-life approximately doubles on average between 4-month-old and 24-month-old mice, with the stability of individual proteins differing among brain regions. Furthermore, we describe the aged neuronal ‘aggregome’, which encompasses 1,726 proteins, nearly half of which show reduced degradation with age. The aggregome includes well-known proteins linked to diseases and numerous proteins previously not associated with neurodegeneration. Notably, we demonstrate that neuronal proteins accumulate in aged microglia, with 54% also displaying reduced degradation and/or aggregation with age. Among these proteins, synaptic proteins are highly enriched, which suggests that there is a cascade of events that emerge from impaired synaptic protein turnover and aggregation to the disposal of these proteins, possibly through microglial engulfment of synapses. These findings reveal the substantial loss of neuronal proteome maintenance with ageing, which could be causal for age-related synapse loss and cognitive decline. Newly developed mouse models that enable cell-specific analyses of proteostasis dynamics across the lifespan of the mice reveal key aspects of neuronal proteostasis with ageing.

  PublisherDOI

• Mapping the nanoscale organization of the human cell surface proteome reveals new functional associations and surface antigen clusters

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-02-17 · 4 citations

  preprintOpen accessSenior authorCorresponding

  The cell surface is a dynamic interface that controls cell-cell communication and signal transduction relevant to organ development, homeostasis and repair, immune reactivity, and pathologies driven by aberrant cell surface phenotypes. The spatial organization of cell surface proteins is central to these processes. High-resolution fluorescence microscopy and proximity labeling have advanced studies of surface protein associations, but the spatial organization of the complete surface proteome remains uncharted. In this study, we systematically mapped the surface proteome of human T-lymphocytes and B-lymphoblasts using proximity labeling of 85 antigens, identified from over 100 antibodies tested for binding to surface-exposed proteins. These experiments were coupled with an optimized data-independent acquisition mass spectrometry workflow to generate a robust dataset. Unsupervised clustering of the resulting interactome revealed functional modules, including well-characterized complexes such as the T-cell receptor and HLA class I/II, alongside novel clusters. Notably, we identified mitochondrial proteins localized to the surface, including the transcription factor TFAM, suggesting previously unappreciated roles for mitochondrial proteins at the plasma membrane. A high-accuracy machine learning classifier predicted over 6,000 surface protein associations, highlighting functional associations such as IL10RB's role as a negative regulator of type I interferon signaling. Spatial modeling of the surface proteome provided insights into protein dispersion patterns, distinguishing widely distributed proteins, such as CD45, from localized antigens, such as CD226 pointing to active mechanisms of regulating surface organization. This work provides a comprehensive map of the human surfaceome and a resource for exploring the spatial and functional dynamics of the cell membrane proteome.

  PublisherOA PDFDOI

• 982 Targeting glycans for cancer immunotherapy

  Regular and Young Investigator Award Abstracts · 2025-11-01

  articleOpen accessSenior author
  PublisherOA PDFDOI

• Color-neutral and reversible tissue transparency enables longitudinal deep-tissue imaging in live mice

  Proceedings of the National Academy of Sciences · 2025-08-26 · 4 citations

  articleOpen access

  Light scattering in biological tissue presents a significant challenge for deep in vivo imaging. Our previous work demonstrated the ability to achieve optical transparency in live mice using intensely absorbing dye molecules, which created transparency in the red spectrum while blocking shorter-wavelength photons. In this paper, we extend this capability to achieve optical transparency across the entire visible spectrum by employing molecules with strong absorption in the ultraviolet spectrum and sharp absorption edges that rapidly decline upon entering the visible spectrum. This color-neutral and reversible tissue transparency method enables optical transparency for imaging commonly used fluorophores in the green and yellow spectra. Notably, this approach facilitates tissue transparency for structural and functional imaging of the live mouse brain labeled with yellow fluorescent protein and GCaMP through the scalp and skull. We show that this method enables longitudinal imaging of the same brain regions in awake mice over multiple days during development. Histological analyses of the skin and systemic toxicology studies indicate minimal acute or chronic damage to the skin or body using this approach. This color-neutral and reversible tissue transparency technique opens opportunities for noninvasive deep-tissue optical imaging, enabling long-term visualization of cellular structures and dynamic activity with high spatiotemporal resolution and chronic tracking capabilities.

  PublisherDOI

• Antibody-lectin chimeras for glyco-immune checkpoint blockade

  Nature Biotechnology · 2025-12-16 · 4 citations

  articleOpen accessSenior authorCorresponding

  Despite the curative potential of checkpoint blockade immunotherapy, many patients remain unresponsive to existing treatments. Glyco-immune checkpoints, which involve interactions of cell-surface glycans with lectin, or glycan-binding, immunoreceptors, have emerged as prominent mechanisms of immune evasion and therapeutic resistance in cancer. Here, we describe antibody-lectin chimeras (AbLecs), a modular system for glyco-immune checkpoint blockade. AbLecs are bispecific antibody-like molecules comprising a cell-targeting antibody domain and a lectin 'decoy receptor' domain that directly binds glycans and blocks their ability to engage inhibitory lectin receptors. AbLecs potentiate cancer cell destruction by primary human immune cells in vitro and reduce tumour burden in a humanized, immunocompetent mouse model, outperforming most existing therapies and combinations tested. By targeting a distinct axis of immunological regulation, AbLecs synergize with blockade of established immune checkpoints. AbLecs can be readily designed to target numerous tumours and immune cell subsets as well as glyco-immune checkpoints, thus representing a potential modality for cancer immunotherapy.

  PublisherDOI

• Induced proximity at the cell surface

  Nature Biotechnology · 2025-03-26 · 14 citations

  reviewOpen accessSenior author
  PublisherOA PDFDOI

• 282 Tumor-Targeting TLR9 Agonist Promotes Antitumor Immune Activity in Intracranial Glioma Model

  Neurosurgery · 2025-03-14

  article

  INTRODUCTION: Immunotherapies involving toll-like receptor 9 (TLR9) agonists can promote anti-tumor immune responses in various preclinical models. However, the adoption of systemically-administered TLR9 agonists for glioblastoma (GBM) is limited by poor trafficking to the tumor and an immunosuppressive tumor microenvironment (TME). Conjugating tumor-targeting peptides represents a potential solution to these issues and may unleash the efficacy of TLR9 agonists in GBM. METHODS: Syngeneic GL261-luc glioma cells were orthotopically implanted in 6–8-week-old female C57BL/6J mice. Mice were intraperitoneally injected with either vehicle (phosphate-buffered saline), 200 ug anti-programmed cell death protein 1 (PD1) antibody, 250 ug PIP-CpG V3, or both anti-PD1 and PIP-CpG V3, on days 10, 12, and 14 post-tumor implantation. Mice were either monitored for survival or euthanized on day 17 for immunological assays. RESULTS: Systemic administration of PIP-CpG V3 monotherapy and combination therapy with anti-PD1 + PIP-CpG V3 increased the median survival of GL261 tumor-bearing mice (PIP-CpG V3: p = 0.049, combination: p = 0.012). Flow cytometry analysis of tumor-bearing brains revealed significantly increased infiltration of CD8+ T cells (PIP-CpG V3: p < 0.0001, combination: p < 0.0001) and CD11b+ MHCII+ CD11c+ dendritic cells (DCs) (PIP-CpG V3: p < 0.0001, combination: p < 0.0001) in groups that received PIP-CpG V3, relative to vehicle mice. Additionally, PIP-CpG V3 therapy induced upregulation of various immune activation markers (CD69, CD86, PD-L1) across different immune cell subsets, including DCs, NK cells, B cells, and other myeloid cells in tumor-bearing brains. CONCLUSIONS: PIP-CpG V3 improved survival of GL261 tumor-bearing mice, both by itself and in combination with anti-PD1. Flow cytometry immunophenotyping indicates that PIP-CpG V3 can remodel the glioma microenvironment, resulting in a higher proportion of CD8+ T cells and DCs as well as upregulation of activation markers on diverse immune subsets.

  PublisherDOI

• Glycocalyx dysregulation impairs blood–brain barrier in ageing and disease

  Nature · 2025-02-26 · 104 citations

  articleOpen accessCorresponding

  Abstract The blood–brain barrier (BBB) is highly specialized to protect the brain from harmful circulating factors in the blood and maintain brain homeostasis 1,2 . The brain endothelial glycocalyx layer, a carbohydrate-rich meshwork composed primarily of proteoglycans, glycoproteins and glycolipids that coats the BBB lumen, is a key structural component of the BBB 3,4 . This layer forms the first interface between the blood and brain vasculature, yet little is known about its composition and roles in supporting BBB function in homeostatic and diseased states. Here we find that the brain endothelial glycocalyx is highly dysregulated during ageing and neurodegenerative disease. We identify significant perturbation in an underexplored class of densely O-glycosylated proteins known as mucin-domain glycoproteins. We demonstrate that ageing- and disease-associated aberrations in brain endothelial mucin-domain glycoproteins lead to dysregulated BBB function and, in severe cases, brain haemorrhaging in mice. Finally, we demonstrate that we can improve BBB function and reduce neuroinflammation and cognitive deficits in aged mice by restoring core 1 mucin-type O-glycans to the brain endothelium using adeno-associated viruses. Cumulatively, our findings provide a detailed compositional and structural mapping of the ageing brain endothelial glycocalyx layer and reveal important consequences of ageing- and disease-associated glycocalyx dysregulation on BBB integrity and brain health.

  PublisherOA PDFDOI

• MFSD6 is an entry receptor for enterovirus D68

  Nature · 2025-03-25 · 27 citations

  articleOpen access
  PublisherOA PDFDOI

• irCLIP-RNP and Re-CLIP reveal patterns of dynamic protein assemblies on RNA

  Nature · 2025-03-26 · 14 citations

  articleOpen access
  PublisherOA PDFDOI

Recent grants

• Glycosylation and Immune Evasion in Urologic Tumors

  NIH · $3.0M · 2019–2026

• NIH Grant R01GM059907

  NIH · $6.2M · 2018

• NIH Grant R01AI051622

  NIH · $6.0M · 2016

• NIH Grant R01GM066047

  NIH · $3.8M · 2015

• Chemical glycobiology tool development: Proximity-based modalities

  NIH · $5.5M · 1999–2029

Frequent coauthors

• Nicholas M. Riley

  University of Washington

  147 shared

• Stacy A. Malaker

  Yale University

  98 shared

• Laura L. Kiessling

  Massachusetts Institute of Technology

  97 shared

• Julie A. Leary

  University of California, Davis

  95 shared

• David Rabuka

  88 shared

• Joseph A. Loo

  University of California, Los Angeles

  87 shared

• Gilbert C. Walker

  University of Toronto

  85 shared

• William L. Jorgensen

  Yale University

  85 shared

Education

• B.S.

  Harvard University

  1988

• Ph.D.

  UC Berkeley

  1993

Awards & honors

• Nobel Prize in Chemistry
• Lemelson-MIT award for inventors
• Whistler Award
• Ernst Schering Prize
• MacArthur Foundation Fellowship