Research

Jura

     lab

UC

SF

University of California, San Franciscohttp://www.ucsf.edu/
CVRIhttp://cvri.ucsf.edu/
CMP Departmenthttp://cmp.ucsf.edu/
 

Overview


The main interest of our laboratory is to understand molecular principles of signal transduction events. We investigate them at the level of enzymatic function and molecular structure of signaling proteins. Our current focus is on understanding how membrane-associated kinases, such as receptor tyrosine kinases, assemble into functional complexes and interface with the plasma membrane. We also investigate alternative non-catalytic roles of kinase scaffolds and seek to identify small molecule inhibitors that target these poorly understood kinase functions in human diseases.



Current Areas of Interest:


Structure-function studies of receptor tyrosine kinase activation mechanism

We use x-ray crystallography and electron microscopy (in collaboration with Yifan Cheng’s lab at UCSF) to gain high resolution insights into ligand-dependent activation of the receptor tyrosine kinase complexes, propagation of conformational changes in the receptor domains across the plasma membrane, and interaction of the receptors with their downstream effectors. To validate our structural models, we use quantitative cell-based functional assays, such as phospo-flow cytometry.


Understanding how membrane participates in cellular signaling

By using various technologies of the in vitro membrane reconstitution, we use synthetic approaches to build the minimal signaling units comprising receptor tyrosine kinases in vitro. This allows us to study how the stoichiometry and kinetic properties of receptor activation are regulated by the membrane environment.


Direct visualization of receptor activation events at cell surface

Spatial and temporal aspects of receptor tyrosine kinase activation in cells decide about the signaling outcome of receptor activation. To capture and understand these essential parameters, in collaboration with Bo Huang’s lab at UCSF we are developing tools for super resolution imaging of receptor activation in response to growth factors in cells.


Non-catalytic functions of protein kinases

Around 10% of all kinases in the human genome do not have catalytic activity, but are essential for cellular homeostasis and frequently misregulated in human diseases. We are interested in elucidating the structural and functional basis for these alternative kinase functions, and ultimately in their modulation by small molecules with the goal of developing effective therapeutics.

Research
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