# Understanding the impact of AAK1 on T cell chemokine receptor expression and chemotaxis

> **NIH NIH R21** · MAYO CLINIC ROCHESTER · 2021 · $238,500

## Abstract

PROJECT SUMMARY/ABSTRACT
T cells infiltrating into the brain directly and indirectly promote neuronal impairment in a wide variety of
neuroinflammatory diseases, including dementia, multiple sclerosis (MS), and epilepsy. Thus, limiting T cell
infiltration into the central nervous system could have therapeutic benefit for these patients. Adapter protein 2
associated kinase 1 (Aak1) was recently identified as an important regulator of T cell chemotaxis into inflamed
tissues in an in vivo forward genetic screen. The primary objective of this project is to understand how AAK1
regulates T cell chemotaxis, with a secondary goal of establishing the translational potential of AAK1 as a
therapeutic target in neuroinflammatory diseases. These goals will be accomplished in two aims. Aim 1 will
determine if AAK1 regulates chemokine receptor expression on the T cell surface using primary T cells. Aim 2
will define the extent to which AAK1 regulates T cell chemotaxis using in vitro migration assays and in vivo T
cell trafficking into the brain using the Theiler’s murine encephalomyelitis virus (TMEV) model of MS. This
proposal has several innovative aspects, including generation of a novel, T cell specific Aak1 knockout mouse,
validation of Aak1 as a genetic regulator of T cell infiltration, functional and mechanistic testing of a novel Aak1
mutant construct, and evaluation of Aak1 as a novel therapeutic target to limit T cell chemotaxis into inflamed
tissue. Successful completion of this project will broadly benefit many disease settings, as findings can easily
be translated to other inflammatory conditions where recruitment of T cells drives pathogenicity and may lead
to better treatments of immunologic diseases.

## Key facts

- **NIH application ID:** 10300774
- **Project number:** 1R21AI155826-01A1
- **Recipient organization:** MAYO CLINIC ROCHESTER
- **Principal Investigator:** Laura Marie Rogers
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $238,500
- **Award type:** 1
- **Project period:** 2021-06-08 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10300774

## Citation

> US National Institutes of Health, RePORTER application 10300774, Understanding the impact of AAK1 on T cell chemokine receptor expression and chemotaxis (1R21AI155826-01A1). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10300774. Licensed CC0.

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