# Solitary chemosensory cell development and function

> **NIH NIH R21** · INDIANA UNIVERSITY INDIANAPOLIS · 2021 · $181,826

## Abstract

PROJECT SUMMARY
 Novel approaches to airway epithelial study have broadened our understanding of its diverse cellular
makeup, developmental regulators, response to injury, and cell interactions involved in local tissue function.
Recent work by our group and others has demonstrated a role for airway solitary chemosensory cells (SCCs)
in detection of irritants within the airway surface liquid, signal transduction through canonical bitter taste
signaling effectors, and initiation of a multifaceted immune response. Interestingly, lineage implications from
RNAseq based approached in mouse and human lung studies suggest a possible relationship between SCCs
and other rare airway cell types including the ionocyte and the neuroendocrine cell.
 Our central hypothesis is that human SCCs encompass a heterogeneous population that is modulated in
the allergic inflammatory setting, and uniquely express cell-specific chemosensory receptors to detect human
disease-associated compounds. This hypothesis has been formulated on the basis of publications and
preliminary data produced in the applicant's laboratory during the K23 mentored research period, and Co-I
Vladar's long-standing interest in airway epithelial repair. To test this—and generate tools for further
mechanistic study—we will utilize a platform of retroviral gene transfer to genetically modify SCCs in human
cell culture. We will pursue two aims: (1) characterization of SCC differentiation using the hTRPM5p-GFP
lentiviral reporter in normal and allergic human primary sinonasal epithelial cell culture; and (2) test human
SCC functional responses to disease-associated airborne irritants using a real-time TRPM5-mCherry/GCaMP6
Ca2+ reporter in primary HSNEC culture.
 Our long-term goal is to determine the functional role(s) of SCCs and chemosensory cell types in airway
epithelial homeostasis, and to translate these findings into a cohesive understanding of airway mucosal
immunity in human health and disease. Notably, limitations of available methods for labeling and isolating this
rare cell type from human tissues have resulted in challenges in translating findings from mouse to human.
 This innovative proposal represents a significant conceptual departure from the status quo, and will utilize
novel methodologies to test specific hypotheses and for general discovery in an area where little is known. The
proposed research is significant because it is expected to advance understanding of how SCCs function as
environmental sensory that regulate epithelial homeostasis. Ultimately, such knowledge has the potential to be
developed into effective therapies for inflammatory airway disorders, a pressing need given the significant
incidence and burden of these diseases.

## Key facts

- **NIH application ID:** 10539379
- **Project number:** 7R21DC019490-02
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** Vijay Ramakrishnan
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $181,826
- **Award type:** 7
- **Project period:** 2021-04-05 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10539379

## Citation

> US National Institutes of Health, RePORTER application 10539379, Solitary chemosensory cell development and function (7R21DC019490-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10539379. Licensed CC0.

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