# Surfaceomic technologies and antibodies to probe cell surface proteomes and their interactomes at unprecedented small scale and high-resolution

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2023 · $572,243

## Abstract

Title: Surfaceomic technologies and antibodies to probe cell surface proteomes and their interactomes
at unprecedented small scale and high-resolution
Project summary
The cell surfaceome is the primary hub that allows cells to sense and respond to changes in their environment,
yet only a minority of the estimated 4000-5000 plasma membrane and secreted proteins have been functionally
characterized. We understand even less about coordinate regulation of the surfaceome, and specifically how the
composition, complexes, distribution, and function of membrane proteins are altered to collectively mediate
changes to cellular phenotypes. Our long-range goal is to systematically understand how cells remodel
their membrane proteome (surfaceome) in health and disease, and to develop antibodies that probe and
modulate these processes. With the support of the R35 MIRA in the last five years, we have extensively
characterized the surfaceome changes induced by oncogene transformation leading to discovery of new
biomarkers, cancer drug targets, and generation of highly specific antibodies. In the next five years, we will
develop new surfaceome technologies for small scale analysis of cell populations, particularly in
neurodegeneration using iPSC derived models and patient-derived samples. We will define the cell surface
protein complexes and interactomes using a high-resolution proximity labeling method enabled by Dexter Energy
Transfer (DET). We plan to interrogate the
interactome of EGFR family receptors in i ii iii
cancer, and cytokine receptors in T-cell
 Ir
activation. We believe the technologies for
small scale surfaceomics and interactomics will
dramatically improve our abilities to map cell
surfaces and their intreactomes in diseases
ranging from cancer, immunology, neurology,
and more. We have produced recombinant Figure 1. Overview of development of surfaceomics technologies.
antibodies to 100s of cell surface proteins using
phage, yeast, and mammalian display, and we anticipate the expanded efforts in understanding the surfaceome
will advance the development of highly selective antibodies that probe and modulate cellular states. We began
this vision in our first R35 grant by defining the surfaceomes induced by specific oncogenes in cancer. Next, we
will greatly expand surfaceomics science to much smaller scales of specialized and primary cells, and much
higher resolution analysis of signaling interactomes.

## Key facts

- **NIH application ID:** 10552328
- **Project number:** 2R35GM122451-06
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** JAMES A WELLS
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $572,243
- **Award type:** 2
- **Project period:** 2017-08-01 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10552328

## Citation

> US National Institutes of Health, RePORTER application 10552328, Surfaceomic technologies and antibodies to probe cell surface proteomes and their interactomes at unprecedented small scale and high-resolution (2R35GM122451-06). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10552328. Licensed CC0.

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