The zebrafish is a versatile vertebrate model organism offering several advantages over mammalian species. For example, the fact that fish embryos and larvae are small and transparent allows in vivo monitoring of development and function of the entire cardiovascular and nervous systems with single-cell resolution. Moreover, advanced molecular genetic techniques permit precise modifications of specific cell types.
Ischemic heart disease associated with acute loss of cardiomyocytes is a major cause of heart failure. The regenerative capacity of the human heart, as in other mammals, is grossly inadequate to compensate for such a catastrophic loss of heart muscles. Despite intensive studies, a successful cell-based therapy to replace the lost cardiac muscles has yet to emerge.
The work in our group focuses on the roles of hematopoietic lineage cells in cardiac repair with the ultimate goal to tackle the limitation of myocardial regeneration. We are taking advantage of the zebrafish unique ability to replenish the injured heart with fully functional cardiac muscles throughout life to elucidate how hematopoietic-cardiac cell interactions contribute to this process and to identify the cellular and molecular regulators responsible for this remarkable regenerative capacity.
The nervous and immune systems engage in bidirectional communications essential for normal functioning of an organism. These interactions play also a central role in the development of disease states in the brain and other organs. For example, brain activity generated in response to psychological stress modulates immunity, thereby impairing defenses against pathogens. On the other hand, immune cells can feedback to regulate central nervous system function and ultimately behavior.
We are currently interested in two lines of research. Our first goal is to understand how innate and adaptive immunity regulates brain activity and behavior in physiological and pathological conditions. Secondly, we aim to reveal how the central nervous system can alter immunity in peripheral tissues in response to changes in the external environment and internal states.
Immune-mediated cardiac-neuronal communications
In the 1920s German physiologist Otto Loewi set a milestone in neuroscience by demonstrating the existence of chemical synaptic transmission, showing that acetylcholine could slow down heart beat. While the control of heartbeat by the nervous systems is today textbook knowledge, we still know very little about the influence of neurons on other aspects of cardiac physiology. For example, it is now recognized that the nervous system can affect the regenerative capacity of the myocardium, but much is left to learn on cellular components and regulatory mechanisms underlying neuronal communications with cardiac-resident and circulating cells recruited to the injured heart.
We aim to understand how the nervous system influence cardiac repair through interactions with elements of the immune system and stem cells.
Main methods used in the lab
Molecular Genetics, Confocal and Two-Photon in vivo Imaging, Cardiac Injury Models, Embryo Manipulation Techniques, Behavioral Assays, Genome-wide expression profiling.