# Modulation of cystogenesis

> **NIH NIH R01** · BRIGHAM AND WOMEN'S HOSPITAL · 2024 · $573,216

## Abstract

Mutations in PKD1 are responsible for over 85% of cases in autosomal dominant polycystic kidney disease
(ADPKD). A number of studies by us and others have implicated that the ADPKD proteins polycystin-1 and -2
(PC1 and PC2) modulate a number of cellular events and signaling pathways such as Ca2+ signaling, JAK-
STAT, mTOR, cyclic AMP (cAMP), and planar cell polarity (PCP). How polycystins modulate these pathways,
however, remains elusive. The sequence of these signaling events is unknown. A major challenge is that many
experiments have been performed using different model systems, different cell types, and under different
conditions. Better understanding of the cystogenic mechanisms and disease progression of ADPKD is a high
priority for clinical care. Our long-term goal of this proposal is to identify and modulate the factors controlling
cyst formation and enlargement in ADPKD using multidisciplinary approaches. We previously reported a
biochemical interaction between PC1 and protein kinase C and casein kinase substrate in neurons 2 (Pacsin
2), a cytoplasmic phosphoprotein that has been implicated in cytoskeletal organization and vesicle trafficking.
By in vitro studies, we found that PC1, Pacsin 2 and N-Wasp are in the same protein complex and deficiency
of either PC1 or Pacsin 2 leads to defects in actin cytoskeleton and cell migration in cultured cells. Here we
propose to extend our study of Pacsin 2 to multiple orthologous mouse models of ADPKD that we have
developed to understand mechanisms suppressing cystogenesis. We aim to develop an in vivo imaging
protocol of cell migration and to elucidate the role of Pascin 2 in cystogenesis using multidisciplinary
approaches including the analysis the cystogenic proteome and phosphoproteome in human and mouse
ADPKD models using the latest quantitative proteomics technology, coupled with innovative bioinformatics
tools.
The proposed studies will likely discover novel therapeutic targets central to the early event(s) in cystogenesis.

## Key facts

- **NIH application ID:** 10798213
- **Project number:** 5R01DK129574-03
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Jing Zhou
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $573,216
- **Award type:** 5
- **Project period:** 2022-05-01 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10798213

## Citation

> US National Institutes of Health, RePORTER application 10798213, Modulation of cystogenesis (5R01DK129574-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10798213. Licensed CC0.

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