UCSF

Extracellular Proteome

The extracellular proteome is one focus of our research.

Understanding and changing cellular behaviors

Our goals

Cells remodel their surface proteomes when they undergo state changes in development, disease, drug treatment, and drug resistance. Our goal is to understand how the surface proteome changes and to develop tools to modulate cells from the outside. Specifically, we want to:

  • characterize how the expression of cell surface proteins is coordinately regulated during cell-state changes using quantitative proteomics and a newly developed multiplexed bar-coded antibody technology called Phage-antibody Next Generation Sequencing (PhaNGS) .

  • understand the biological consequences of cell state changes through interactomics, CRISPR-based functional genomics, and mechanistic biochemistry.

  • generate renewable recombinant antibodies using our industrialized Antibot platform at an unprecedented scale.
    diagram

Our desired results

We seek to identify and modulate the function of cell surface proteins most relevant to diseases, drug treatment, and drug resistance. We can use antibodies developed in-house to probe and functionally modulate important surface proteins, surface protein complexes, or to detect downstream phosphorylation events. We are also developing new ways to bioconjugate antibodies using N-terminal ligation with subtiligase and site-specific conjugation for detection, combination, and drug conjugates. Cell surface targets are of keen interest to the pharmaceutical industry yet most therapeutic efforts are directed to only a handful of the several thousand annotated surface proteins. Understanding how the surface proteome changes and developing recombinant antibodies to interrogate and target understudied surface proteins is our most rapidly expanding project area and an area where we have only begun to scratch the surface (pun intended).

An extensively collaborative effort

Our work is significantly augmented through direct collaborations with:

and active collaborations with professors including:

We obtain additional funding from: