I. Mechanism: Discover principles of life at molecular and cellular levels

Question: What fundamental rules govern the dance of molecules inside and outside cells? How do molecules assemble, signal, and adapt to orchestrate cellular responses? What emergent behaviors arise from the interactions of individual molecules?

Passion: We are interested in the logic of molecular and cellular interactions. By revealing these hidden natural principles, we want to understand life not just in fragments, but as integrated, dynamic systems.

Approach: Biochemistry, structural biology, biophysics, cell biology

Relevant work: 

Xia, S., Zhang, Z., Magupalli, V.G., Pablo, J.L., Dong, Y., Vora, S.M., Wang, L., Fu, T.-M., Jacobson, M.P., Greka, A., Lieberman, J., Ruan, J. and Wu, H., 2021. Gasdermin D pore structure reveals preferential release of mature interleukin-1. Nature. (Link) 

Ruan, J., Xia, S., Liu, X., Lieberman, J. and Wu, H., 2018. Cryo-EM structure of the gasdermin A3 membrane pore. Nature. (Link) 

II. Function: Elucidate the roles of living systems in health and disease

Question: What do molecules and cells actually do in living organisms, beyond isolated assays? How do these living systems know when to attack or stand down? Why do similar molecular and cellular events lead to distinct physiological and pathological outcomes?

Passion: We are enthusiastic about revealing the connections between molecular or cellular events and physiological or pathological consequences, building a transition from basic biology to translational application.

Approach: Immunology, in vivo modeling, physiology, pathology

Relevant work: 

Kong, Q., Xia, S., Pan X., Ye, K., Li, Z., Li, H., Tang, X., Sahni, N., Yi, S.S., Liu, X., Wu, H., Elowitz, M.B., Lieberman, J., and Zhang, Z., 2023. Alternative splicing of GSDMB modulates killer lymphocyte-triggered pyroptosis. Science Immunology. (Link) 

Zhang, Z., Zhang, Y., Xia, S., Kong, Q., Li, S., Liu, X., Junqueira, C., Meza-Sosa, K.F., Mok, T.M.Y., Ansara, J., Sengupta, S., Yao, Y., Wu, H. and Lieberman, J., 2020. Gasdermin E suppresses tumour growth by activating anti-tumour immunity. Nature. (Link) 

III. Design: Build synthetic circuits to program biological behavior

Question: Can we write molecular instructions that rewire cell fate? What if proteins could act like software, sensing inputs, making decisions, and triggering actions? How can synthetic designs answer questions that natural systems cannot resolve?

Passion: We design synthetic circuits at gene and protein levels that endow cells with new capabilities, unlocking possibilities for therapy, diagnostics, and discovery. We seek to engineer unnatural pathways that do not just observe biology, but reshape it.

Approach: Synthetic biology, chemical biology, engineering, systems biology

Relevant work: 

Xia, S., Lu, A.C., Tobin, V., Luo, K., Moeller, L., Shon, D.J., Du, R., Linton, J.M., Sui, M., Horns, F. and Elowitz, M.B., 2024. Synthetic protein circuits for programmable control of mammalian cell death. Cell. (Link)

Chen, Z., Linton, J.M., Xia, S., Fan, X., Yu, D., Wang, J., Zhu, R. and Elowitz, M.B., 2024. A synthetic protein-level neural network in mammalian cells. Science. (Link)

Our research is fortunate to receive support from

© Shiyu Xia Lab, University of California, Berkeley. All rights reserved.