# Unraveling molecular Complexity of Mitral Valve Disease using single cell and Spatial Multi-Omics analysis"

> **NIH NIH R01** · YALE UNIVERSITY · 2024 · $462,133

## Abstract

PROJECT SUMMARY
Mitral valve prolapse (MVP), a condition affecting 2-3% of the general populace, is typified by irregular thickening
of valve leaflets. The histopathological modifications associated with MVP are well known, yet a comprehensive
understanding of the specific molecular structures and their impact on the disease's onset remains elusive. Bulk
RNA-sequencing has been utilized to investigate gene expression in MVP, although inconsistencies between
these data and those derived from traditional IHC and RT-PCR analysis have been observed. This discrepancy
may be due to the fact that averaged expression cannot accurately portray heterogeneity across different cellular
populations. At present, the study of MVP mitral valve leaflet samples using single-cell approaches is
considerably limited. Moreover, spatial omics methodologies, capable of illustrating the spatial heterogeneity
within tissue microenvironments, have not been applied to MVP research. To address this knowledge gap, we
intend to construct a single-cell and spatial molecular atlas using mitral valve leaflet samples from both MVP
patients and healthy contributors. In-depth data analysis will enable us to elucidate the molecular underpinnings
of the disease. In this endeavor, we will focus on three specific objectives: 1) we aim to accurately identify cell
subpopulations and molecular states in MVP using single-nucleus multi-omics sequencing; 2) we plan to
characterize MVP's mitral valve tissue through spatially resolved transcriptomic, epigenomic, and proteomic
techniques such as spatial-CITE-seq and spatial ATAC-seq; 3) we will extend our research to construct a
molecular atlas of Marfan syndrome MVP utilizing single-cell and spatial omics analysis. In sum, the molecular
data and insights gained from this research will facilitate further exploration into the diverse cell populations and
tissue microenvironment associated with MVP.

## Key facts

- **NIH application ID:** 10858142
- **Project number:** 1R01HL173271-01
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Yang Liu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $462,133
- **Award type:** 1
- **Project period:** 2024-09-01 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10858142

## Citation

> US National Institutes of Health, RePORTER application 10858142, Unraveling molecular Complexity of Mitral Valve Disease using single cell and Spatial Multi-Omics analysis" (1R01HL173271-01). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10858142. Licensed CC0.

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