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
Mechanisms of cell communication governing
tissue inflammation, repair, and homeostasis
Inflammatory immune responses are essential for protecting organisms against injury, infection, and disease, but excessive inflammation can damage bystander tissues and compromise biological function. To prevent this, mammals have evolved a complex array of signaling molecules and receptors that ensure the appropriate protection and repair of host tissues during and after inflammation. Failure of these homeostatic systems can result in chronic inflammation, autoimmunity, and cancer — diseases with rapidly increasing prevalence in modern society.
The Saxton Lab studies the mechanisms of intercellular signaling that control tissue inflammation, repair, and homeostasis, with the goal of developing new therapeutics to harness these pathways in disease.
Our interdisciplinary research program uses cutting edge approaches in protein engineering (directed evolution, rational design), structural biology (cryo-EM), receptor pharmacology, and mouse models of inflammation to understand and control inflammatory signaling at the atomic, cellular, and organismal levels.
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.
Key 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.
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.
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.
Other work
1. 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.
2. 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.
3. 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.
4. 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.
5. 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.
6. 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.
7. Saxton, R. A., & Sabatini, D. M. (2017). mTOR Signaling in Growth, Metabolism, and Disease. Cell, 168(6), 960–976. (Review)
8. 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.
9. 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.
10. 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.
11. 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.
12. 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.
*Equal contribution
Lab Members
Robert 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
Leia Sun, PhD
Postdoctoral Researcher
Molecular and Cell Biology
leiasun [at] berkeley.edu
Alexander Dasque
Graduate Student
Biophysics
abdasque [at] berkeley.edu
Yichen (Eason) Li
Master's Student (MPH)
Infectious Disease and Vaccinology
eason.li [at] berkeley.edu
Miko Mallari
Research Associate
Molecular and Cell Biology
miko.mallari [at] berkeley.edu
Jiucheng Ding
Research Associate
Molecular and Cell Biology
jd2263 [at] berkeley.edu
Katie Fang
Research Associate
Molecular and Cell Biology
katiefang [at] berkeley.edu
Evander Li
Undergraduate
Molecular & Cell Biology
evander.li [at] berkeley.edu
Mallak Ali
Undergraduate
Microbial Biology
mallakali [at] berkeley.edu
Join us!
The Saxton Lab is 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.
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.
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.
Masters Students:
Current masters students who are enrolled in national or international programs and hoping to join our lab as visiting students (6-12 month duration) to complete their thesis are welcome. Research experience in biology, biochemistry or chemistry is an advantage.
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