# Girk3 in bone biology and disease

> **NIH NIH K99** · MAYO CLINIC ROCHESTER · 2024 · $104,867

## Abstract

PROJECT SUMMARY / ABSTRACT
The goals of this proposal are to: 1) obtain experimental skills and career training necessary to develop an
independent research program investigating mechanisms of bone development and disease, and 2) characterize
a novel target of bone remodeling called G protein-gated inwardly-rectifying K+ channel 3 (Girk3), a key regulator
of potassium flux and physiological processes. Our data demonstrate that Girk3-/- mice develop high bone mass
after skeletal maturity and have low interleukin-1 beta (IL-1β) and other circulating cytokines. The overall
objective of this proposal is to test the hypothesis that Girk3 deletion enhances bone density in adult skeletons
by altering the secretion of IL-1β and other monocyte-derived cytokines that modify bone resorption. During the
mentored K99 phase, the specific aims are to identify how deletion of Girk3 in monocytes affects bone mass
(Aim 1) and to determine how Girk3 regulates cytokine production by blood and bone marrow monocytes (Aim
2). Methods used to evaluate the role of Girk3 in bone remodeling will include dynamic and static
histomorphometry, osteoblast and osteoclast differentiation assays, cytometry by time-of-flight (CyTOF), single
cell RNA-sequencing (scRNA-seq), and bioinformatics. Completion of this aim will facilitate my transition into the
independent R00 phase when the specific aim (Aim 3) will be to determine if Girk3 deletion can prevent bone
loss in a murine model of osteoporosis via inhibition of IL-1β. The K99 phase will be conducted at Mayo Clinic
and will focus on obtaining mentored training in professional development through meetings with a curated
mentorship team, regular attendance and presentations at research seminars and national research
conferences, participating in workshops on grantsmanship and responsible conduct in research, and seeking
out networking opportunities, as well as conducting the experiments in Aims 1 and 2 and publishing the results.
The R00 phase will be conducted in my independent laboratory and will focus on completion and publication of
Aim 3 and developing an R01 application based on the results. The proposed plan synergizes new skills in
osteoclast and ion channel biology, unbiased spectometry, single cell RNA sequencing and bioinformatics, and
bone histomorphometry with prior expertise in endocrinology and osteoblast biology to create my own unique
research trajectory. The career development plan and research strategy outlined in this application will produce
a robust foundation for an independent research career in musculoskeletal biology.

## Key facts

- **NIH application ID:** 10835072
- **Project number:** 5K99AR080745-02
- **Recipient organization:** MAYO CLINIC ROCHESTER
- **Principal Investigator:** Samantha R Weaver
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $104,867
- **Award type:** 5
- **Project period:** 2023-05-01 → 2024-09-03

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10835072

## Citation

> US National Institutes of Health, RePORTER application 10835072, Girk3 in bone biology and disease (5K99AR080745-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10835072. Licensed CC0.

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