Garg Lab
The Garg Lab focuses on identifying genetic contributors to the most common type of birth defect: congenital heart diseases (CHD). Its team aims to dissect the molecular mechanisms by which these genetic abnormalities disrupt cardiac developmental pathways to cause cardiovascular disease. The Garg Lab is also interested in the genetic contributors to progressive heart valve and aortic aneurysmal diseases, which often affect CHD survivors.
Dr. Garg and his team have studied families with inherited cardiovascular diseases, including CHD, cardiomyopathies and cardiac arrhythmias, to identify novel etiologic genes and/or pathogenic variants and published the first research linking mutations in GATA4 and NOTCH1 to cardiac septation defects and heart valve disease, respectively, in humans (Garg, Nature 2003; Garg, Nature, 2005).
Over time, research in the Garg Lab has evolved to leverage the latest advances in genomic technologies, including chromosomal microarray and, more recently, exome and whole genome sequencing approaches (LaHaye, Circulation: Cardiovascular Genetics 2016; Manivannan, PLOS Genetics 2020). His team was also one of the first to identify pathogenic chromosomal copy number changes in children with CHD and additional congenital anomalies (Richards, Pediatric Research 2008).
The Garg Lab has since studied how these genes and specific mutations disrupt normal heart development and gene functions, respectively, by using cell-based assays and, in select cases, the development of murine models (Misra, PLOS Genetics, 2012; Koenig, Journal of the American Heart Association, 2016; LaHaye, Disease Models & Mechanisms, 2019). This work has led to insights into the etiology of both congenital heart defects and adult-onset cardiovascular diseases, which are often co-morbid conditions for adult congenital heart disease survivors (Koenig, JCI Insight 2017; Majumdar, Science Advances, 2021).
Additionally, to further define the role of gene-environment interactions in CHD, the team has expanded its research to include efforts to better understand how environmental factors, specifically maternal diabetes, affect cardiac developmental pathways (Basu, JCI Insight, 2017).
The research efforts in the Garg Lab have involved a diverse group of over 50 trainees, ranging from postdoctoral and research fellows with both medical and doctorate degrees, graduate and medical students, and undergraduate and high school students. Support for the lab’s research efforts includes current and past extramural funding from the National Institutes of Health (NIH), including the National Heart, Lung, and Blood Institute (NHLBI), American Heart Association (AHA), March of Dimes, Children’s Heart Foundation and Saving tiny Hearts Society.
Featured Publications
- A novel pathogenic GATA6 variant identified in a family with congenital heart disease, childhood-onset diabetes mellitus and necrotizing enterocolitis
- Generation and Characterization of a human induced pluripotent stem cell line heterozygous for a NOTCH1 mutation (NCHi014-A)
- Congenital Aortic Valve Stenosis: from pathophysiology to molecular genetics and the need for novel therapeutics
- Single cell RNA-seq analysis of aortic valve interstitial cells demonstrate the regulation of integrin signaling by nitric oxide
- Nitric oxide prevents aortic valve calcification by S-nitrosylation of Usp9x to activate Notch signaling
Ongoing Research Support
Funding | Research | Years Awarded |
R01HL144009 | Epigenetic Mechanisms Underlying Maternal Diabetes Associated Cardiac Malformations | 2019-2025 |
R21HL161823 | A Multi-omic approach towards improving candidate gene identification and variant prioritization in patients with congenital heart disease |
2022-2024 |
R01HL175924 | Mechanisms and therapeutics for congenital aortic valve disease | 2024-2028 |
Join Our Team!
The Garg Lab is growing. If you are interested in joining our team as a gap year trainee, research intern, research assistant, etc., please send a cover letter and a CV/Resume to Vidu.Garg@NationwideChildrens.org.