Our laboratory studies how coronary vessels of the heart develop during embryogenesis and how they regenerate following cardiac injury. Our long-term goal is to discover novel developmental mechanisms while contributing knowledge towards the advancement of clinical treatments for cardiovascular disease.
Key to our findings have been a departure from classical approaches of studying mammalian organ development, i.e. broad level analyses through histological sections. Instead, we interrogate how single cells behave within intact organs. Using this approach, we compiled 3D maps of coronary development and repair and obtained whole transcriptomes of the single cells within these maps Full knowledge of cell lineage, transcriptional state, and position of cells within developing and regenerating hearts provides an invaluable resource for our research.
Vertebrate organ development and regeneration requires the establishment of a blood vessel network that supports each tissue’s physiological needs. The blood vasculature contains diverse cell types organized into a stereotyped vessel hierarchy that ensures efficient transport of blood and oxygen. In addition, each organ’s vascular bed develops tissue-specific characteristics that are required for optimal function. Vascular development in many organs can be broadly divided into two steps: 1. Sprouting angiogenesis to create an immature vascular plexus and 2. Plexus remodeling to form arteries, capillaries, and veins. However, many questions remain about how organ-specific vascular beds are constructed, such as what is the identity of inductive factors produced by target tissues and paracrine factors produced by the vessel cells themselves as well as how mechanical forces imparted by blood flow influence the developmental process. Finally, we take the lessons learned from development and apply them to injury models to to grow new coronary vessels to enhance cardiac recovery.
