Saxton Lab
Welcome to the Saxton Lab!
Division of Immunology and Molecular Medicine
Departments of Molecular and Cell Biology and Chemistry
University of California, Berkeley
Research
Understanding and engineering tissue–immune
crosstalk to control inflammation
Immune responses rely on communication between immune cells and the tissues they protect. Cytokines and related signaling molecules transmit these signals, instructing tissue-resident cells such as epithelia and fibroblasts how to respond to infection, injury, and inflammation. While these pathways are essential for host defense and tissue repair, dysregulated signaling can drive chronic inflammatory diseases.
The Saxton Lab studies how tissue-intrinsic cytokine signaling governs inflammation, repair, and homeostasis, with the goal of developing new precision therapeutics to control these pathways in disease.
Our interdisciplinary research integrates structural biology, immunology, and protein engineering to both understand and reprogram inflammatory signaling pathways. We combine cryo-EM, biochemical and cellular approaches, and mouse models with protein engineering and computational design to probe cytokine receptor signaling across molecular, cellular, and organismal scales.
1. Resolution of inflammation
Chronic, unresolved inflammation is a central feature of many human diseases including autoimmunity, cardiovascular disease, neurodegeneration, and cancer. We seek to understand the mechanisms of immune cell signaling that dampen and resolve inflammation, in order to harness these pathways therapeutically.
Our recent work has focused on the key anti-inflammatory cytokine interleukin-10 (IL-10). By solving the cryo-EM structure of the IL-10 receptor complex, we were able to rationally design myeloid selective IL-10 variants with enhanced therapeutic properties. These molecules are currently being developed for clinical use in autoimmune and chronic inflammatory disease.
Publications
For a complete list see Google Scholar.
Select Publications
1. Saxton, R. A.*, Caveney, N. A.*, Moya-Garzon, M. D., Householder, K. D., Rodriguez, G.E., Burdsall, K. A., Long, J. Z., Garcia, K. C. (2023). Structural insights into the mechanism of leptin receptor activation. Nature communications, 14(1797).
2. Caveney, N. A.*, Saxton, R. A.*, Waghray, D.*, Glassman, C. R., Tsutsumi, N., Hubbard, S. R., Garcia, K. C. (2023). Structural basis of Janus Kinase trans-activation. Cell reports, 42(3), 112201.
3. Saxton, R. A., Glassman, C. R., & Garcia, K. C. (2022). Emerging principles of cytokine pharmacology and therapeutics. Nature reviews. Drug discovery, 10.1038/s41573-022-00557-6.
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4. Saxton, R. A., Henneberg, L. T., Calafiore, M., Su, L., Jude, K. M., Hanash, A. M., & Garcia, K. C. (2021). The tissue protective functions of interleukin-22 can be decoupled from pro-inflammatory actions through structure-based design. Immunity, 54(4), 660–672.e9.
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5. Saxton, R. A., Tsutsumi, N., Su, L. L., Abhiraman, G. C., Mohan, K., Henneberg, L. T., Aduri, N. G., Gati, C., & Garcia, K. C. (2021). Structure-based decoupling of the pro- and anti-inflammatory functions of interleukin-10. Science, 371(6535), eabc8433.
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Other work
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1. Abhiraman, G.C, Householder, K.D., Rodriguez G.E., Glassman, C.R., Saxton R.A., ... Retticker-Flynn, N.E., Garcia K.C. (2025). Redirecting immune signaling with cytokine adaptors. Nature communications. 16, 2432.
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1. Caveney N.A., Rodriguez G.E., Pollmann C., .., Saxton R.A., Piehler J., Garcia K.C. (2024). Structure of the interleukin-5 receptor complex exemplifies the organizing principle of common beta cytokine signaling. Molecular Cell. 84(10):1995-2005.e7.
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2. Abhiraman, G.C., Bruun, T.U.J., Caveney, N.A., Su, L.L., Saxton, R.A., Yin, Q., Tang, S., Davis, M.M., Jude, K.M, Garcia, K.C. (2023). A structural blueprint for interleukin-21 signal modulation. Cell reports, 42(6), 112657.
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3. Valenstein, M.L.*, Rogala, K.B.*, Lalgudi, P.V., Brignole, E.J., Gu, X., Saxton, R.A., Chantranupong, L., Kolibius, J., Quast, J.-P., and Sabatini, D.M. (2022). Structure of the nutrient-sensing hub GATOR2. Nature, 607(7919), 610–616.
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4. Glassman, C. R.*, Tsutsumi, N.*, Saxton, R. A., Lupardus, P. J., Jude, K. M., & Garcia, K. C. (2022). Structure of a Janus kinase cytokine receptor complex reveals the basis for dimeric activation. Science, 376(6589), 163–169.
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5. Mohan, K.*, Ueda, G.*, Kim, A. R., Jude, K. M., Fallas, J. A., Guo, Y., Hafer, M., Miao, Y., Saxton, R. A., Piehler, J., Sankaran, V. G., Baker, D., & Garcia, K. C. (2019). Topological control of cytokine receptor signaling induces differential effects in hematopoiesis. Science, 364(6442), eaav7532.
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6. Mena, E. L., Kjolby, R., Saxton, R. A., Werner, A., Lew, B. G., Boyle, J. M., Harland, R., & Rape, M. (2018). Dimerization quality control ensures neuronal development and survival. Science, 362(6411), eaap8236.
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7. Gu, X.*, Orozco, J. M.*, Saxton, R. A., Condon, K. J., Liu, G. Y., Krawczyk, P. A., Scaria, S. M., Harper, J. W., Gygi, S. P., & Sabatini, D. M. (2017). SAMTOR is an S-adenosylmethionine sensor for the mTORC1 pathway. Science, 358(6364), 813–818.
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8. Saxton, R. A., & Sabatini, D. M. (2017). mTOR Signaling in Growth, Metabolism, and Disease. Cell, 168(6), 960–976. (Review)
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9. Saxton, R. A., Chantranupong, L., Knockenhauer, K. E., Schwartz, T. U., & Sabatini, D. M. (2016). Mechanism of arginine sensing by CASTOR1 upstream of mTORC1. Nature, 536(7615), 229–233.
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10. Chantranupong, L., Scaria, S. M., Saxton, R. A., Gygi, M. P., Shen, K., Wyant, G. A., Wang, T., Harper, J. W., Gygi, S. P., & Sabatini, D. M. (2016). The CASTOR Proteins Are Arginine Sensors for the mTORC1 Pathway. Cell, 165(1), 153–164.
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11. Saxton, R. A., Knockenhauer, K. E., Wolfson, R. L., Chantranupong, L., Pacold, M. E., Wang, T., Schwartz, T. U., & Sabatini, D. M. (2016). Structural basis for leucine sensing by the Sestrin2-mTORC1 pathway. Science, 351(6268), 53–58.
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12. Wolfson, R. L.*, Chantranupong, L.*, Saxton, R. A., Shen, K., Scaria, S. M., Cantor, J. R., & Sabatini, D. M. (2016). Sestrin2 is a leucine sensor for the mTORC1 pathway. Science, 351(6268), 43–48.
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13. Chantranupong, L.*, Wolfson, R. L.*, Orozco, J. M., Saxton, R. A., Scaria, S. M., Bar-Peled, L., Spooner, E., Isasa, M., Gygi, S. P., & Sabatini, D. M. (2014). The Sestrins interact with GATOR2 to negatively regulate the amino-acid-sensing pathway upstream of mTORC1. Cell reports, 9(1), 1–8.
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*Equal contribution
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Lab Members
Robert A. Saxton, PhD
Principal Investigator
Assistant Professor of Immunology & Molecular Medicine (IMM) and Molecular Therapeutics (MTx)
Department of Molecular & Cell Biology
Department of Chemistry
rsaxton [at] berkeley.edu
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Leia Sun, PhD
Postdoctoral Researcher
Molecular and Cell Biology
Priyanka Garg, PhD
Postdoctoral Researcher
Molecular and Cell Biology
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Alex Soohoo, PhD
Postdoctoral Researcher
Molecular and Cell Biology
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Alexander Dasque
Graduate Student
Biophysics
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Isaac Kaba
Graduate Student
Chemical Biology
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Yichen (Eason) Li, MPH
Graduate Student
Molecular and Cell Biology
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Kyle Anderson
Graduate Student
Molecular and Cell Biology
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Ivan Davidek
Graduate Student
Chemical Biology
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Muji Ahmed
Graduate Student
Metabolic Biology
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Jiucheng Ding
Staff Research Associate
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Vera Fang
Undergraduate Researcher
Molecular and Cell Biology
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Kevin Li
Staff Research Associate
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Param Malik
Undergraduate Researcher
Molecular and Cell Biology
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Lab Alumni Current Position
Katie Fang, Undergrad Stanford PhD program
Mallak Ali, Undergrad Research associate at CZI Imaging Institute
Miko Mallari, SRA UCSF Computational Drug Discovery MS Program
Evander Li, Undergrad/SRA Stanford PhD program
Ferrin Antony, Postdoc Scientist, Calico
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Join us!
The Saxton Lab is a diverse group of scientists with backgrounds in immunology, biochemistry, protein engineering, and structural biology. We are unified by a passion for dissecting immune cell signaling pathways and developing next generation immune-targeted therapies. We are located in the 3rd floor of the Li Ka Shing Center at UC Berkeley, within the departments of Molecular and Cell Biology (MCB) and Chemistry.
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Graduate Students:
The Saxton Lab is affiliated with several graduate programs at UC Berkeley including MCB, Biophysics, and Chemical Biology, and we are currently accepting rotation students from all programs.
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Postdocs:
Motivated postdocs with expertise in immunology, biochemistry or structural biology are encouraged to apply. Please include a cover letter, your CV, and contact information for three references.
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Candidates interested in any of these opportunities are welcome to contact us directly.
Li Ka Shing Center for Biomedical Research
University of California, Berkeley
Berkeley, CA 94720
saxtonlabucb[at]gmail.com