Formation of heart and vasculature follow a complex series of steps that involve interplay of stimulatory and inhibitory signaling, guidance molecules and cross-talk among numerous cell types. A growing understanding of these events is already shedding light on many complex clinical problems and will likely result in development of new regenerative approaches to the treatment of a wide variety of cardiac illnesses. The following areas are being studied by YCVRC investigators:
Vascular and lymphatic development: A. Eichmann, S-W Jin, M. Simons, S. Nicoli
Large vessel development: D. Greif
Hemogenic endothelium: K. Hirschi
The vascular and the nervous system are the first two systems to develop and they share a remarkable number of features including the overall network architecture and many signaling molecules and receptors. In addition, there is a remarkable cross-talk between the two systems with peripheral nerves guiding development of peripheral arteries and arterial blood supply supporting nerve growth. This interaction extends even further with the vasculature playing an important role in modulating nervous system plasticity during development and in adult tissues.
Neural guidance of the vasculature: A. Eichmann, C. Ruhrberg (UCL)
Neurovascular CNS niche: K. Hirschi, J-L Thomas (Neurology)
Cellular responses to a variety of soluble and extracellular matrix signals are at the heart cardiovascular biology. A thorough understanding of this process can guide understanding of numerous cardiovascular pathologies from formation of arterial-venous malformations to development of cardiac hypertrophy to to blood pressure regulation. The ability to manipulate these signaling events is critical to development of new classes of therapeutic agents that can promote process such as arteriogenesis or lymphangiogenesis, increase contractility of the failing heart or reverse myocardial hypertrophy.
Endothelial and smooth muscle signaling: J. Bender, H. Chun, K. Martin, W. Sessa (Pharmacology), M. Simons
Myocardial signaling: D. Tirziu, L. Young
Technology advances in DNA sequencing and array analysis of gene expression have enabled comprehensive approaches to the analysis of many common and not so common cardiovascular problems. The YCVRC genetics program seeks to understand genetic basis of a number of cardiovascular illnesses including early onset coronary artery disease, metabolic syndrome, sudden cardiac death and atrial fibrillation. Much of this work is carried out in close collaboration with CV geneticists at UCL.
Genetics, genomics & pharmacogenomics: J. Hwa, A. Mani, W. McKenna (UCL),
The goal of stem cell biology investigations at YCVRC is to develop a through understanding of processes involved in cell differentiation with the view towards developments of stem cell-based regenerative therapies for cardiac and neurological diseases. At the same time, we are exploring the utility of iPS-derived defined cell types from patients with complex illnesses for molecular diagnostics. These investigations are being carried out in close collaborations with Department of Neurology, Yale Stem Cell Center and UCLStem cells: K. Hirschi, Y. Quyang.