Mikaela Karin Ribi

All Publications

• Glycosite mapping and in situ mass spectrometry imaging of MUC2 glycopeptides via on-slide mucinase digestion. Nature communications Lowery, S. C., Ribi, M. K., Chongsaritsinsuk, J., Tran, I. P., Grimsley, G., Stubler, R., Mahoney, K. E., Lucas, T. M., Charkoftaki, G., Santos-Neto, A., Varki, N., Vasiliou, V., Angelo, M., Drake, R. R., Malaker, S. A. 2026

  Abstract

  Current analytical techniques are limited in their ability to interrogate the mechanistic relationship between aberrant mucin glycosylation and malignancy. Herein, we describe a method for mapping specific mucin glycoforms in diseased tissue, enabling correlation of the tumor glycan profile with malignant features. Following on-tissue digestion with mucinase StcE, matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI) deduces the spatial distribution of mucinous O-glycopeptides that are subsequently identified using liquid chromatography coupled to mass spectrometry (LC-MS). Our coupled MS approach reveals a striking mucin 2 (MUC2) expression pattern in three colorectal mucinous adenocarcinomas, in which different glycoforms clearly stratify regions within each tumor. The LC-MS experiments obtain glycoproteomic sequence coverage of MUC2's mucin domains in unprecedented depth, and we also present evidence for an endogenous O-acetylated GalNAc. Overall, this proof-of-concept work underscores the potential of this technique to drive research in oncology and beyond.

  View details for DOI 10.1038/s41467-026-72853-3

  View details for PubMedID 42098121

• Antibody-lectin chimeras for glyco-immune checkpoint blockade. Nature biotechnology Stark, J. C., Gray, M. A., Ibarlucea-Benitez, I., Lustig, M., Bond, A., Cho, B., Govil, I., Luu, T., Priestley, M. J., Veth, T. S., Errington, W. J., Bruncsics, B., Ribi, M. K., Williams, L. A., Sarkar, C. A., Wisnovsky, S., Riley, N. M., Morrissey, M. A., Valerius, T., Ravetch, J. V., Bertozzi, C. R. 2025

  Abstract

  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.

  View details for DOI 10.1038/s41587-025-02884-6

  View details for PubMedID 41402487

  View details for PubMedCentralID 7537339

• Multi-omic landscape of human gliomas from diagnosis to treatment and recurrence. Cancer cell Piyadasa, H., Oberlton, B., Ribi, M., Leow, K., Ranek, J. S., Averbukh, I., Amouzgar, M., Liu, C. C., Franchina, D. G., Greenwald, N. F., McCaffrey, E. F., Kumar, R., Ferrian, S., Tsai, A. G., Filiz, F., Fullaway, C. C., Bosse, M., Varra, S. R., Kong, A., Sowers, C., Gephart, M. H., Nuñez-Perez, P., Yang, E., Travers, M., Schachter, M. J., Liang, S., Santi, M. R., Bucktrout, S., Gherardini, P. F., Connolly, J., Cole, K., Barish, M. E., Brown, C. E., Oldridge, D. A., Drake, R. R., Phillips, J. J., Okada, H., Prins, R., Bendall, S. C., Angelo, M. 2025

  Abstract

  Gliomas are among the most lethal cancers, with limited treatment options. To uncover hallmarks of therapeutic escape and tumor microenvironment (TME) landscape, we applied spatial proteomics, transcriptomics, and glycomics to 670 lesions from 310 adult and pediatric patients. Single-cell analysis shows high B7H3+ tumor cell prevalence in glioblastoma (GBM) and pleomorphic xanthoastrocytoma, while most gliomas, including pediatric cases, express targetable tumor antigens in less than 50% of tumor cells, potentially explaining trial failures. Paired samples of isocitrate dehydrogenase (IDH)-mutant gliomas reveal recurrence driven by tumor-immune spatial reorganization, shifting from T cell and vasculature-associated myeloid cell-enriched niches to microglia and CD206+ macrophage-dominated tumors. Multi-omic integration identified N-glycosylation as the best classifier of grade, while the immune transcriptome best predicted GBM survival. Provided as a community resource, this study offers a framework for glioma targeting, classification, outcome prediction, and a baseline of TME composition across all stages.

  View details for DOI 10.1016/j.ccell.2025.11.006

  View details for PubMedID 41386224

• Multi-omic landscape of human gliomas from diagnosis to treatment and recurrence. bioRxiv : the preprint server for biology Piyadasa, H., Oberlton, B., Ribi, M., Ranek, J. S., Averbukh, I., Leow, K., Amouzgar, M., Liu, C. C., Greenwald, N. F., McCaffrey, E. F., Kumar, R., Ferrian, S., Tsai, A. G., Filiz, F., Fullaway, C. C., Bosse, M., Varra, S. R., Kong, A., Sowers, C., Gephart, M. H., Nuñez-Perez, P., Yang, E., Travers, M., Schachter, M. J., Liang, S., Santi, M. R., Bucktrout, S., Gherardini, P. F., Cole, K., Barish, M. E., Brown, C. E., Oldridge, D. A., Drake, R. R., Phillips, J. J., Okada, H., Prins, R., Bendall, S. C., Angelo, M. 2025

  Abstract

  Gliomas are among the most lethal cancers, with limited treatment options. To uncover hallmarks of therapeutic escape and tumor microenvironment (TME) evolution, we applied spatial proteomics, transcriptomics, and glycomics to 670 lesions from 310 adult and pediatric patients. Single-cell analysis shows high B7H3+ tumor cell prevalence in glioblastoma (GBM) and pleomorphic xanthoastrocytoma (PXA), while most gliomas, including pediatric cases, express targetable tumor antigens in less than 50% of tumor cells, potentially explaining trial failures. Longitudinal samples of isocitrate dehydrogenase (IDH)-mutant gliomas reveal recurrence driven by tumor-immune spatial reorganization, shifting from T-cell and vasculature-associated myeloid cell-enriched niches to microglia and CD206+ macrophage-dominated tumors. Multi-omic integration identified N-glycosylation as the best classifier of grade, while the immune transcriptome best predicted GBM survival. Provided as a community resource, this study opens new avenues for glioma targeting, classification, outcome prediction, and a baseline of TME composition across all stages.

  View details for DOI 10.1101/2025.03.12.642624

  View details for PubMedID 40161803

  View details for PubMedCentralID PMC11952471

• Chemical generation of checkpoint inhibitory T cell engagers for the treatment of cancer. Nature chemistry Szijj, P. A., Gray, M. A., Ribi, M. K., Bahou, C., Nogueira, J. C., Bertozzi, C. R., Chudasama, V. 2023

  Abstract

  Bispecific T cell engagers (BiTEs), a subset of bispecific antibodies (bsAbs), can promote a targeted cancer cell's death by bringing it close to a cytotoxic T cell. Checkpoint inhibitory T cell engagers (CiTEs) comprise a BiTE core with an added immunomodulatory protein, which serves to reverse cancer-cell immune-dampening strategies, improving efficacy. So far, protein engineering has been the main approach to generate bsAbs and CiTEs, but improved chemical methods for their generation have recently been developed. Homogeneous fragment-based bsAbs constructed from fragment antigen-binding regions (Fabs) can be generated using click chemistry. Here we describe a chemical method to generate biotin-functionalized three-protein conjugates, which include two CiTE molecules, one containing an anti-PD-1 Fab and the other containing an immunomodulatory enzyme, Salmonella typhimurium sialidase. The CiTEs' efficacy was shown to be superior to that of the simpler BiTE scaffold, with the sialidase-containing CiTE inducing substantially enhanced T cell-mediated cytotoxicity in vitro. The chemical method described here, more generally, enables the generation of multi-protein constructs with further biological applications.

  View details for DOI 10.1038/s41557-023-01280-4

  View details for PubMedID 37488375

  View details for PubMedCentralID 6182456

• ANTIBODY-LECTIN BISPECIFICS FOR GLYCO-IMMUNE CHECKPOINT BLOCKADE Stark, J., Gray, M., Wisnovsky, S., Ibarlucea-Benitez, I., Riley, N., Ribi, M., Ravetch, J., Bertozzi, C. BMJ PUBLISHING GROUP. 2022: A1254

  View details for DOI 10.1136/jitc-2022-SITC2022.1209

  View details for Web of Science ID 000919423401318