Welcome to the Saxton Lab!

Division of Immunology and Molecular Medicine

Departments of Molecular and Cell Biology and Chemistry

University of California, Berkeley

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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 control these pathways in disease.

 

Our multidisciplinary 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.

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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.

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Publications

For a complete list see Google Scholar.

Key Publications

 

1. 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.

2. 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.

3. 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. 

4. 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. 

5. 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. 

Other work

1. 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. Structure of the nutrient-sensing hub GATOR2. Nature, 607(7919), 610–616.

2. 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. 

3. 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. 

4. 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 survivalScience, 362(6411), eaap8236. 

5. 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. 

6. Saxton, R. A., & Sabatini, D. M. (2017). mTOR Signaling in Growth, Metabolism, and Disease. Cell, 168(6), 960–976. (Review)

7. 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. 

8. 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. 

9. 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 mTORC1Cell reports, 9(1), 1–8. 

*Equal contribution

 

News

10/1/22: Saxton Lab opens at UC Berkeley!
 
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Robert A. Saxton, PhD

Principal Investigator

Assistant Professor of Immunology and Molecular Medicine

Department of Molecular and Cell Biology

Department of Chemistry

Lab Members

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Join us!

The Saxton Lab is located in the 5th 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 biochemistry, structural biology, immunology, or metabolism are encouraged to apply. Please include a cover letter, your CV, and contact information for three references.

Undergraduate Students:

UC Berkeley undergraduate students who are interested in conducting biomedical research and being part of our multidisciplinary team are welcome to apply.  

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

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