# Signaling mechanisms and functions related to patho-physiology of vascular, lung and blood systems

> **NIH NIH R35** · YALE UNIVERSITY · 2020 · $912,314

## Abstract

Project Summary:
My laboratory is interested in understanding molecular basis and functions for two signaling
pathways that use seven transmembrane receptors in their signaling transduction. One of the
pathways is mediated by G protein-coupled receptors, and the other is activated by Wnt
proteins. We have been using a combination of biochemical, molecular and cell biological,
transgenic, genomic, proteomic, structural and chemical biological approaches to discover novel
signaling mechanisms and investigate their functions in vitro and in vivo. In this R35 application,
I intend to streamline our current four research projects that are pertinent to NHBLI missions
under one funding mechanism. Two of the projects are current funded by NHBLI. These four
projects are: 1) To test the hypothesis that the initial break of the symmetry may arise from PM
PI4P polarization caused by plasma membrane deformation as the result of cell attachment.
Polarized PM PI4P defines the “uropod” and thus the initial cellular polarity, upon which further
polarization stimulated by chemoattractants is extended. 2) To investigate the sustained
signaling pathway for regulation of fibroblast migration and its therapeutic potential in treating
pulmonary fibrosis. 3) To Investigate the hypothesis that increased exocytosis is a pathogenic
basis for CCM disease. 4) To investigate MEKK3 as being a negative regulator of NADPH
oxidase 2 (NOD2) and potential therapeutic target for acute respiratory distress syndrome.
Each of the project is highly innovative and would exert a strong impact in their respective field.
In addition, we are generating the new leads coming from these high risk/high reward studies
that include functional genomic screens based on the CRISPR/Cas9 and RNAi technologies.
Thus, this R35 mechanism would not only allow streamlining our grant application and
management so that we can better focus our effort on research, but also afford us the flexibility
to fully and efficiently pursue the new leads coming from these high risk/high reward studies.
Our track record strongly indicates our readiness, capability, and success to pursue subjects
that we deem to be of high-impact even though they fall outside our initial intents.

## Key facts

- **NIH application ID:** 9851421
- **Project number:** 5R35HL135805-04
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Dianqing Wu
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $912,314
- **Award type:** 5
- **Project period:** 2017-02-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9851421

## Citation

> US National Institutes of Health, RePORTER application 9851421, Signaling mechanisms and functions related to patho-physiology of vascular, lung and blood systems (5R35HL135805-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9851421. Licensed CC0.

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