# Discovering how oncogenes  remodel the surfaceome of cells

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2021 · $534,869

## Abstract

Title: Discovering how oncogenes remodel the surfaceome of cells
Abstract: The cell surface is the primary hub for cells to communicate with the outside world. Cancer cells
have numerous challenges for survival and we hypothesize many of
these start at the cell surface made up of some 3000-4000 proteins.
Our primary goal is to systematically understand how cancer cells
remodel their membrane proteomes (surfaceomes) during
oncogenic transformation to survive. We propose to develop
enabling technologies for surfaceomics at the population, single cell,
and tissue level. We will generate foundational data sets to
understand the molecular logic and signaling mechanisms behind
the coordinated remodeling events that drive cellular transformation.
(Fig 1). We will focus our studies on mutationally activated KRAS
and five other highly proliferative oncogenes (EGFR, BRAF, MEK,
Akt and PI3K) that together are found in nearly half of all human
cancers. We will study how these oncogenes induce coordinate
changes in the surfaceome compared to isogenic cells of the same
type, in patient derived cancer cells and tissues. We propose new
mass spectrometry-based methods to allow for quantification of
membrane proteins using two complementary enrichment methods
that target surface glycans or surface N-terminal α-amines. We will
also develop a new, highly sensitive and multiplexed technology
(phage-antibody next generation sequencing, or PhaNGS) to
simultaneously detect 100s of surface proteins in very small
Figure 1. (A) To understand how
oncogenes such as KRAS induce
massive cellular changes we will (B)
develop new technologies to
measure surfaceome changes to
understand coordinate regulation,
and identify new drug targets.
samples or even single cells. The Antibiome Center, which I direct, in collaboration with the Recombinant
Antibody Network, has produced recombinant antibodies to 100s of cell surface proteins using Fab-phage
display. Each Fab-phage is essentially a DNA barcoded antibody because it has a functional Fab displayed
from the phage particle with the DNA encoding it inside. PhaNGS has tremendous potential for highly
multiplexed, inexpensive and ultrasensitive means of probing 1000s of cells or cell lines for changes in their
surfaceomes. I am excited that these studies will reveal how coordinate remodeling of membrane protein
teams contributes to cell state changes. I believe we will also discover new biomarkers and cancer drug
targets.

## Key facts

- **NIH application ID:** 10212408
- **Project number:** 5R35GM122451-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** JAMES A WELLS
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $534,869
- **Award type:** 5
- **Project period:** 2017-08-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10212408

## Citation

> US National Institutes of Health, RePORTER application 10212408, Discovering how oncogenes  remodel the surfaceome of cells (5R35GM122451-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10212408. Licensed CC0.

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