# Investigating the Role of Dach1 in Artery Specification and Collateral Artery Development

> **NIH NIH F31** · STANFORD UNIVERSITY · 2020 · $34,268

## Abstract

Coronary artery disease is the leading cause of death worldwide and development of new
therapeutic strategies could reduce mortality. Collateral arteries connect arteries to one another
and provide multiple routes for coronary circulation. In patients with coronary artery disease,
those that have well-developed collateral arteries have a reduced rate of mortality.
Unfortunately, due to our poor understanding of the basic mechanisms responsible for artery
growth, there are no therapies to increase collateral artery coverage.
 In order to find novel genes which regulate artery development, we generated a
transgenic mouse line that over expressed the transcription factor Dach1 in endothelial cells.
Using whole mouse immunostaining and confocal microscopy, we found that Dach1 over
expression mice had increased artery and collateral artery coverage during development.
Through a combination of in vitro and in vivo experiments we went on to find that Dach1 over
expression increased expression increased the expression of arterial genes and decreased
venous gene expression supporting a model where Dach1 induces the specification of artery
endothelial cells.
 The goal of this proposal is to 1) understand how the pathway activated by Dach1
increases arterial cell specification and 2) test if increasing collateral artery coverage though
Dach1 overexpression can protect against myocardial infarction. We will find the factors that act
downstream of Dach1 to initiate artery specification by genetically or pharmacologically
inhibiting candidate factors in the Dach1 overexpression background and visualizing artery
formation using confocal microscopy. In addition, we will use the mouse coronary artery ligation
model to test if adult mice over expressing Dach1 can make more collateral arteries post-
ligation and increase survival. Answering these questions will elucidate new molecular
regulators of artery growth that could be targeted therapeutically in patients with coronary artery
disease.
 This research will be conducted in the laboratory of Dr. Kristy Red-Horse at Stanford
University. Both the faculty mentor and institution are well suited for the scientific and career
development of the applicant. Specifically, the applicant will benefit from abundant opportunities
for scientific presentations and writing practice, mentorship of junior graduate students, access
to state of the art facilities for experimenting with mouse genetics, weekly meetings with Dr.
Red-Horse, and close collaboration with Dr. Dan Bernstein who will lead the surgical studies.

## Key facts

- **NIH application ID:** 9959195
- **Project number:** 5F31HL147410-02
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Brian Christopher Raftrey
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $34,268
- **Award type:** 5
- **Project period:** 2019-06-01 → 2021-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9959195

## Citation

> US National Institutes of Health, RePORTER application 9959195, Investigating the Role of Dach1 in Artery Specification and Collateral Artery Development (5F31HL147410-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9959195. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*