# Multi-omic investigation of the adiposity-lipid intersection and its role in cardiovascular disease risk

> **NIH NIH K99** · MASSACHUSETTS GENERAL HOSPITAL · 2024 · $171,450

## Abstract

ABSTRACT
Excess body fat, referred to as “adiposity”, is a major contributor to heart disease, the leading cause of death
worldwide. Anti-obesity medications (AOMs) designed to reduce excess body fat not only help with weight loss
but also significantly decrease the risk of heart disease. However, it is unknown whether this reduction in risk is
solely due to weight loss or if AOMs influence other contributing risk factors, such as elevated lipid levels (e.g.,
cholesterol and triglycerides), which are strongly linked to heart disease and adiposity.
In this research proposal, we will evaluate how adiposity alters the biological mechanisms regulating blood lipid
levels by leveraging the genetic nature of lipids and adiposity, and large-scale datasets with clinical and multi-
omics data—genomics, transcriptomics, and proteomics—to (1) measure interaction effects between adiposity
and genetic DNA variants on lipid levels; (2) evaluate how genetically determined volumes of adipose tissue
affect lifetime trajectories of lipid levels and heart disease risk; and (3) examine how risk factors in addition to
lipid levels, such as high blood pressure and hyperglycemia, mediate the relationship between AOMs and heart
disease. Completing these research aims will assist in identifying key biological pathways at the adiposity-lipid
intersection and provide insight into whether a risk reduction of heart disease by AOMs is due to mechanisms
beyond weight loss.
This project will be led by Dr. Dron, a computational geneticist with expertise in lipid and lipoprotein metabolism,
clinical and population cohorts, and disease risk assessment. Dr. Dron has developed a comprehensive plan to
complete the above research aims and further her career development by expanding upon her current expertise
with training in adipose biology, obesity, and advanced statistical modeling techniques. This supports her goal
of becoming an independent researcher using genetic-based approaches to investigate new ways to enhance
heart disease prediction, prevention, and treatment by better understanding the biological relationship and
interaction between adiposity and heart disease risk factors.
Dr. Dron’s exceptional advisory team will directly support her career development. Her primary mentor, Dr.
Pradeep Natarajan, is a prominent leader in cardiovascular genomics. The additional members of Dr. Dron’s
advisory team include scientists with diverse experiences in biostatistics, causal inference models, adiposity,
obesity, AOMs, and multi-omic analyses of complex traits. Dr. Dron’s outstanding advisory team and training
plan, coupled with the collaborative environment and extensive resources for innovative genetic research at the
Center for Genomic Medicine and Broad Institute of MIT and Harvard, will facilitate her transition into an
independent research career.

## Key facts

- **NIH application ID:** 10948413
- **Project number:** 1K99HL175031-01
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Jacqueline Shirley Dron
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $171,450
- **Award type:** 1
- **Project period:** 2024-09-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10948413

## Citation

> US National Institutes of Health, RePORTER application 10948413, Multi-omic investigation of the adiposity-lipid intersection and its role in cardiovascular disease risk (1K99HL175031-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10948413. Licensed CC0.

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