# Characterization of Novel Signaling Pathways Involved in Water Balance Disorders

> **NIH NIH K08** · MASSACHUSETTS GENERAL HOSPITAL · 2020 · $54,000

## Abstract

PROJECT SUMMARY/ABSTRACT
Maintenance of water homeostasis is a vital function of the kidneys and is essential for
adaptation to terrestrial life. To reabsorb water effectively, vasopressin (VP) is released to
induce aquaporin-2 (AQP2) phosphorylation and actin cytoskeletal remodeling within kidney
principal cells in the collecting ducts, which increases apical membrane expression of AQP2.
Dysregulation of AQP2 trafficking results in disorders of water balance; decreased AQP2
membrane expression causes nephrogenic diabetes insipidus (NDI), whereas an increase in
plasma membrane AQP2 is associated with fluid retention in the syndrome of inappropriate
ADH secretion (SIADH), congestive heart failure and cirrhosis. While VP/cAMP/PKA is the
major signaling pathway that facilitates AQP2 membrane trafficking and water reabsorption, the
process is in fact far more complex, and can be induced or inhibited by other signaling
pathways. One such “alternative” pathway involves the epidermal growth factor receptor
(EGFR), whose inhibition induces AQP2 membrane accumulation and phosphorylation similar
to VP, but bypasses V2R, cAMP and PKA, and my goal is to deepen our understanding of the
crosstalk between VP and EGFR pathways that modulate AQP2, with a long term career goal to
characterize the role of this novel signaling pathways in dysregulated water retention observed
in patients with SIADH, congestive heart failure and liver cirrhosis, in order to eventually design
therapies to alleviate disease symptoms encountered in the clinic.
For the last year and a half, I have been making significant progress in dissecting the pertinent
pathways between VP and EGFR that regulate water balance. However, as I am focusing on
my research career development, life not only brings us surprises, but also concerns about
interruption in research progress. Therefore, I am applying for this new NIH-NIDDK
Administrative Supplement in order to hire a technician during my maternity leave, expected to
span between early to mid-July to early October 2020, in order to preserve or even increase
research productivity. The Brown Laboratory, including my mentor Dr. Dennis Brown, my close
collaborator Dr. Richard Bouley, and I will maximize the intellectual and technical resources to
ensure progress during my leave, and I will remain updated on the progress to resume full
productivity upon my return. This research proposal is carved out of Aim 1 of my parent K08,
and the proposed experiments are carefully designed and expected to be completed by the end
of the supplemental period. Obtaining this supplement funding would provide highly valuable
support at this critical time of my research career.

## Key facts

- **NIH application ID:** 10165964
- **Project number:** 3K08DK115901-03S1
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Pui Wen Cheung
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $54,000
- **Award type:** 3
- **Project period:** 2018-09-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10165964

## Citation

> US National Institutes of Health, RePORTER application 10165964, Characterization of Novel Signaling Pathways Involved in Water Balance Disorders (3K08DK115901-03S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10165964. Licensed CC0.

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