Mariko Morimoto

Research Interests

Modular and efficient reprogramming of the immune system is a compelling strategy to treat a variety of challenges including cancer, autoimmunity, chronic disease, and infection. For example, immunotherapy such as checkpoint blockade has revolutionized the landscape of cancer treatment. Yet, we are far from unlocking its full potential: >80% of patients remain either ineligible or unresponsive to existing checkpoint inhibitors, highlighting the need for new paradigms to retrain our immune systems.

To address this need, research in the Morimoto group will center around chemical immunology, where we will develop chemical approaches to discover and target immune-regulating mechanisms. One focus will be on glycans, or sugars, that coat the surface of every cell in the body and facilitate a broad spectrum of immune responses by engaging lectins (glycan binding proteins). These chemical motifs remain underutilized in medicinal chemistry and immunotherapy largely due to the complexity of these glycan-lectin interactions. We seek to devise new experimental and computational approaches to deconvolute these interactions and access glycan-inspired modalities that can drug previously untargeted glyco-immune pathways.

A second focus will be on synthesizing small molecules/biologics that modulate specific protein- protein interactions (PPIs) in immune cells to recircuit and restore their healthy function. In addition to the design of these highly immunomodulatory molecules, we seek to develop innovative methods that enable us to discover them under physiologically relevant and high throughput conditions.

As a highly interdisciplinary research group, trainees in the Morimoto lab will develop strong skills in synthetic organic chemistry, chemical biology, biomolecular engineering, and cell biology/immunology.

Selected Publications

• Maddess, M. L.; Cleator, E.; Morimoto, M.; Goodyear, A.; Dieguez-Vazquez, A.; Gibb, A.; Kirtley, A.; Christensen, M.; Song, C. H.; Peng, F.; Alam, M.; Keen, S. P. and Oliver, S. F. "Process Development of a Tricyclic Diazepine-Based IDH1 Mutant Inhibitor" 2024 Organic Process Research & Development, 28 (6), pp.2343-2354. DOI: 10.1021/acs.oprd.4c00171.
• Morimoto, M.; Till, N. A. and Bertozzi, C. R. "Tumor Immune Cell Targeting Chimeras (TICTACs) for Targeted Depletion of Macrophage-Associated Checkpoint Receptors" 2023 bioRxiv. DOI: 10.1101/2023.12.06.570444.
• Nguyen, Q.; Xia, K. T.; Zhang, Y.; Chen, N. H.; Morimoto, M.; Pei, X. K.; Ha, Y.; Guo, J. H.; Yang, W. L.; Wang, L. P.; Bergman, R. G.; Raymond, K. N.; Toste, F. D. and Tantillo, D. J. "Source of Rate Acceleration for Carbocation Cyclization in Biomimetic Supramolecular Cages" 2022 Journal of the American Chemical Society, 144 (25), pp.11413-11424. DOI: 10.1021/jacs.2c04179.
• Maddess, M. L.; Cleator, E.; Morimoto, M.; Goodyear, A.; Dieguez-Vazquez, A.; Gibb, A.; Kirtley, A.; Wang, J.; Qi, J.; Kong, L. Z.; Alam, M.; Keen, S.; Oliver, S. F.; Wen, X. and Lam, Y. H. "Development of a Stereoselective Synthesis of (1R,4R)- and (1S,4S)-2-Oxa-5-Azabicyclo[2.2.2]Octane" 2022 Organic Process Research & Development, 26 (3), pp.640-647. DOI: 10.1021/acs.oprd.1c00098.
• Morimoto, M.; Cao, W.; Bergman, R. G.; Raymond, K. N. and Toste, F. D. "Chemoselective and Site-Selective Reductions Catalyzed by a Supramolecular Host and a Pyridine-Borane Cofactor" 2021 Journal of the American Chemical Society, 143 (4), pp.2108-2114. DOI: 10.1021/jacs.0c12479.
• Morimoto, M.; Bierschenk, S. M.; Xia, K. T.; Bergman, R. G.; Raymond, K. N. and Toste, F. D. "Advances in Supramolecular Host-Mediated Reactivity" 2020 Nature Catalysis, 3 (12), pp.969-984. DOI: 10.1038/s41929-020-00528-3.