The importance of basement membranes for cardiovascular development and disease

Congential heart disease affects approximately one percent of all children born worldwide. This multidisciplinary project will combine novel 3D imaging, using synchrotron-based phase contrast micro-CT, with cell and molecular biology for improved understanding of congenital heart defects and cardiovascular function. The primary focus will be the importance of basement membranes for cardiovascular development and disease.

Specifically, we will explore the importance of the basement membrane component laminin by use of mice that lack the laminin delta-1 subunit in cardiomyocytes and smooth muscle cells (SMCs) or lack the laminin alpha2 subunit, as seen in certain forms of human muscular dystrophy. 

Preliminary synchrotron-based imaging data shows heart defects in the mutant mice. Those defects will be explored in detail and tissue sections, as well as isolated primary cells from the mouse strains, will be used for mechanistic studies. 

Novel techniques to integrate molecular biology with advanced 3D imaging to understand extracellular matrix deposition and regulatory mechanisms in a three dimensional context will also be developed.

IGNITE Fellow - Oscar van der Have

Oscar van der Have began his journey in experimental research as a medical student at Lund University. After graduating as a medical doctor in 2020, he pursued a PhD in Vessel Wall Biology. Today, he combines his passion for clinical care and research as an IGNITE Fellow in the Tran-Lundmark lab, while also training as a resident in pediatric cardiology at the Pediatric Heart Center, Skåne University Hospital in Lund. 

Congenital heart defects are the most common form of birth malformation in humans, yet the underlying mechanisms remain incompletely understood. By combining synchrotron-based imaging of genetically modified mice with cellular-level mechanistic studies, his project aims to uncover how laminins contribute to heart development and disease. The insights gained may pave the way for new strategies to better understand, and ultimately prevent, congenital heart conditions.

Main Principal Investigator

• Karin Tran Lundmark

Co-supervisors

• Madeleine Durbeej-Hjalt
• Vinay Swaminathan