Meet the PI: Nathan VanDusen, Ph.D.

Dr. VanDusen joined the Indiana University School of Medicine Cardiac Developmental Biology group during the summer of 2022, as an Assistant Professor of Pediatrics. The lab’s major technical focuses include genome editing, functional genomics, and genetic engineering. We seek to creatively apply these disciplines to the fields of cardiac development and disease, with current major focuses on cardiomyocyte maturation, cardiac regeneration, gene therapy systems development, and heart failure.

Development and Maturation

During normal heart development cardiomyocytes undergo dramatic changes in gene expression and phenotype between birth and adulthood. This process is called cardiomyocyte maturation. In contrast, stem cell derived cardiomyocytes fail to mature, which limits their utility. Furthermore, cardiomyocyte maturation coincides with loss of regenerative capacity, which is a major barrier for development of cardiac regenerative therapies. To address these challenges we are currently using epigenomics and functional genomics to thoroughly characterize transcriptional control of crucial maturational processes.

Precise Genome Editing

Somatic cell precise gene editing has tremendous potential for treating a broad range of diseases, especially those with a genetic basis. In a recent study, we demonstrated that CRISPR/AAV-mediated precise genome editing can occur with surprisingly high efficiencies in the mouse heart. However, efficiency varies greatly between different target loci, and even at ideal loci there remains room for improvement. Current studies in the VanDusen Lab aim to better characterize the molecular mechanisms governing CRISPR/AAV-mediated homology-directed repair, with the goal of engineering gene therapy strategies with improved safety and efficacy.

Adult Cardiac Disease

Studies on maturation can naturally be extended to the disease state, such as pathological cardiomyocyte hypertrophy, where reactivation of components of the immature gene program is frequently observed. Although some transcriptional regulators of hypertrophy have been identified, systematic unbiased in vivo approaches to identifying key regulatory programs are lacking. The VanDusen Lab aims to address this deficiency by employing a variety of high-throughput functional genomics methodologies to identify key disease pathways and regulators. These methods will provide insights into the molecular mechanisms of hypertrophy and have the potential to inspire novel therapeutics.