# T-box transcription factor Tbx2 in coronary vascular development and disease

> **NIH NIH R01** · INDIANA UNIVERSITY INDIANAPOLIS · 2020 · $465,365

## Abstract

PROJECT SUMMARY
Coronary heart disease (CHD) is a leading cause of death worldwide and it affects approximately two-thirds of
patients with severe class IV heart failure, threatening more than 13 million Americans’ life today. Although the
traditional risks for CHD is well recognized, it is largely unknown how the genetic factors regulate the
pathogenesis of CHD. In particular, it is unclear whether the mutations of the genetic factors have any negative
impacts on the coronary vascular formation, and whether the malformed coronary vessels lead to susceptibility
to CHD in human. T-box (Tbx) genes encode transcription factors (TFs) that play essential roles in a wide
range of organs’ development. Mutations in T-box genes are highly associated with human congenital
diseases. We recently identified a previously unknown, specific Tbx2 expression in the coronary vessels.
Through a series of newly generated mouse models, we found that mice with Tbx2 mutations do not form
coronary vasculature properly, and mutants develop cardiac fibrosis with heart failure at adult stage. We further
sequenced human patients with premature CHD, and identified TBX2 mutations on the same amino acid.
These mutations lead to coronary artery smooth muscle cell growth arrest. Our overarching hypothesis is that
Tbx2 transcriptional program plays central roles for coronary smooth muscle formation and function, and the
mutated human TBX2 may result in malformed coronary vasculature. Our objectives are to apply genetic and
biochemical approaches to study the biology of Tbx2, to gain comprehensive knowledge concerning how this
critical TF regulates the downstream genes and govern coronary formation during gestation, whether Tbx2
genetic program is required for sustaining the coronary structure after birth, and whether the dysregulated
Tbx2 transcriptional program leads malformed coronary vessels and susceptibility to CHD. In this program, we
will characterize the genetic role of Tbx2 in the coronary vascular formation, and define the transcriptional
network of Tbx2 in the coronary vessels. Our study will address central questions concerning coronary
vascular development and disease.

## Key facts

- **NIH application ID:** 9879763
- **Project number:** 5R01HL131735-04
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** chenleng cai
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $465,365
- **Award type:** 5
- **Project period:** 2019-03-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9879763

## Citation

> US National Institutes of Health, RePORTER application 9879763, T-box transcription factor Tbx2 in coronary vascular development and disease (5R01HL131735-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9879763. Licensed CC0.

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