# Mitochondrial translocator protein: a target for bronchodilation

> **NIH NIH R01** · THOMAS JEFFERSON UNIVERSITY · 2021 · $404,250

## Abstract

Project Summary
 Effective management of asthma requires regulating airway smooth muscle (ASM) contractility to prevent or
reverse bronchoconstriction. This is primarily achieved by use of direct bronchodilators (e.g., β-agonists), by anti-
inflammatory agents (e.g., corticosteroids) either alone or in combination. However, effective management is
lacking, as an estimated 55% of all asthmatics have suboptimal control. All current bronchodilator drugs have
limitations which respect to efficacy or safety. We propose a novel approach of targeting a mitochondrial protein,
the 18 kDa Translocator Protein (TSPO), as a means of bronchodilation/bronchoprotection. Our central
hypothesis is that potent, efficacious agonists of TSPO can be developed and employed as effective
bronchodilatory/bronchoprotection drugs. Three aims are proposed to test this hypothesis. In Aim 1, using in
vitro (primary airway smooth muscle cells; ASM), ex vivo (murine and human rings and precision cut lung slices),
and in vivo models (smTspo-/- mice), we will establish TSPO as a druggable target to promote relaxation of ASM.
In Aim 2, we will determine the mechanistic basis of TSPO regulation of ASM contraction by assessing the roles
of PKA, and mitochondrial Ca2+ and ROS, on signaling events known to regulate cross bridge cycle (regulatory
myosin light chain 20 and myosin phosphatase phosphorylation) or actin polymerization state (F/G actin ratio).
Lastly, in Aim 3 we will employ molecular modeling to design and synthesize new ligands for TSPO, with an
emphasis on generating new drugs that demonstrate superior binding properties and improved efficacy. These
will be tested in cell and tissue model systems employed in Aim 1. The proposed studies represent an innovative
approach to establish an asthma management strategy that overcomes the current limitations of efficacy and
safety. Moreover, the proposed mechanistic studies will provide new insight into how to optimally target the
mitochondria to regulate contractile signaling and function in ASM.

## Key facts

- **NIH application ID:** 10298047
- **Project number:** 1R01HL153602-01A1
- **Recipient organization:** THOMAS JEFFERSON UNIVERSITY
- **Principal Investigator:** Ajay Nayak
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $404,250
- **Award type:** 1
- **Project period:** 2021-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10298047

## Citation

> US National Institutes of Health, RePORTER application 10298047, Mitochondrial translocator protein: a target for bronchodilation (1R01HL153602-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10298047. Licensed CC0.

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