# Rapid evolution and bacterial evasion by a primate cell adhesion protein

> **NIH NIH F32** · UNIVERSITY OF OREGON · 2021 · $66,390

## Abstract

Proteins that interact with pathogens are among the most rapidly evolving in animal genomes, but how they
can undergo such dramatic change while maintaining essential functions is a fundamental mystery.
Carcinoembryonic antigen-related cell adhesion molecule (CEACAM) family proteins have a wide range of
adhesive, developmental and immunological roles at vertebrate epithelial surfaces. Besides important cellular
functions, CEACAMs are targeted by bacterial ‘adhesin’ proteins to support host colonization. Contrary to their
important ‘housekeeping’ functions, preliminary analyses suggest several CEACAMs are evolving rapidly in
primates, particularly in the binding domain recognized by bacterial adhesins. This indicates pressure to avoid
pathogen binding may accelerate CEACAM evolution. I hypothesize bacterial evasion drives CEACAM evolution
in humans and related primates with consequences for pathogen immunity and host physiologic functions.
 This proposal will investigate the evolution and functional consequences of binding between primate
CEACAM proteins and bacterial adhesins, using primate CEACAM1 and the pathogenic bacteria Helicobacter
pylori as a model system. CEACAM1-HopQ binding promotes H. pylori infection and injection of the oncoprotein
CagA into host cells, leading to gastric inflammation and cancer development. My preliminary experiments
demonstrate that rapid evolution of CEACAM1 in primates controls H. pylori binding between species. Using
phylogenetic and population genetic analyses to trace recent CEACAM evolution in humans and primates, Aim
I will pinpoint evolutionary patterns and molecular determinants of adhesion recognition within host populations.
Altered HopQ binding due to variation at identified residues will be measured in vitro with purified tagged-
CEACAM1 variants and isogenic H. pylori strains carrying different HopQ alleles. Aim II will determine how HopQ
and CEACAM1 variation impacts pathogenicity of H. pylori using cellular signals of binding to cells expressing
CEACAM1 variants. This includes association of host cells with H. pylori, induction of proinflammatory cytokines
and CagA phosphorylation. Aim III will assess homodimerization of CEACAM1 homologs and the ability of
CEACAM1 variation to alter downstream regulatory signaling using interactions with natural killer cells or the
induction of cytokines through CEACAM binding to chimeric protein constructs. This work will reveal how proteins
can evolve to evade pathogens while maintaining essential ‘housekeeping’ functions. Results could ultimately
inform treatment of H. pylori infections and screening and therapy for cancer and other genetic disorders.
 This work will be conducted at the University of Oregon under the guidance of my co-sponsors Dr.’s Barber and
Guillemin. The research environment and training program provide copious chances for technical and professional
development, including training in scientific communication through public presentation and p...

## Key facts

- **NIH application ID:** 10189481
- **Project number:** 5F32AI147565-02
- **Recipient organization:** UNIVERSITY OF OREGON
- **Principal Investigator:** EmilyClare P Baker
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $66,390
- **Award type:** 5
- **Project period:** 2020-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10189481

## Citation

> US National Institutes of Health, RePORTER application 10189481, Rapid evolution and bacterial evasion by a primate cell adhesion protein (5F32AI147565-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10189481. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*