The Srivastava lab is focused on the gene networks that guide the development of the heart, seeking to understand how aberrations in these pathways can cause congenital heart disease, and how they can use this knowledge to generate new cardiac cells to repair heart damage.
One powerful approach they use is creating models of heart disease in a dish by reprogramming human cells from patients carrying mutations in cardiac developmental genes, editing them with CRISPR technology and analyzing changes at the single cell level. This has led them to discover perturbations in pivotal genetic pathways that contribute to disease, and identified the nodes that can be therapeutically targeted to restore heart cells to normal function.
Disease Areas
- Congenital Heart Disease
- Heart Failure
- Cardiac Valve Disease
- Aging
Areas of Expertise
- CRISPR and Gene Editing
- Stem Cells and iPS Cells
- Developmental Biology
- Human Genetics
- Regenerative Medicine
Lab Focus
- Modeling human cardiovascular diseases using single-cell approaches in animal models and induced pluripotent stem cells from patients with genetically defined disease.
- Investigating how combinations of human mutations or polymorphisms in cardiac developmental genes predispose to disease.
- Identifying targetable signaling, transcriptional, and translational nodes that can be manipulated for regenerative medicine or other therapeutic approaches to directly reprogram non-myocytes into new cardiomyocytes for cardiac regeneration.
Research Impact
Srivastava’s lab leveraged the lessons of cardiac developmental biology to directly reprogram resident non-muscle cells in the mouse heart into cells that function like heart muscle cells, effectively regenerating heart muscle after damage. This new paradigm of harnessing endogenous cells to regenerate organs may be broadly applicable to other organs.
Similarly, the team used knowledge of developmental cell-cycle regulators to unlock the post-mitotic state in adult cardiomyocytes and stimulate enough stable cell division to regenerate cardiac muscle in the adult. They also revealed the mechanisms underlying human disease caused by mutations in cardiac developmental regulators using human iPS cells, and used this knowledge to screen for novel therapeutic approaches to disease.
