Area of study:

Our lab studies how the force provided by blood flow (i.e., hemodynamic force) regulates cardiovascular development in mouse and zebrafish model organisms. Specifically, we are interested in understanding how hemodynamic force regulates blood vessel maturation and heart morphogenesis. Also, we aim to discover the signaling pathways that become activated in response to hemodynamic force. Finally, in a new project, we are interested in environmental toxicology screening, with the goal of identifying potential teratogens that impact cardiovascular development.

Our studies focus on these four aspects.

I: Determining the role of smooth muscle cells in stabilizing blood vessel trees
Once vessel trees form their hierarchy, blood vessels begin to mature by becoming surrounded by another layer of cells called vascular smooth muscle cells (vSMCs). Our studies have revealed that hemodynamic force is required for proper formation of the vSMC layer in developing blood vessels. We aim to further understand how this process is regulated.

I. Determine the influence of hemodynamic force on mammalian heart development                                                                 Studies in avian and zebrafish embryos have shown that heart development is perturbed under abnormal hemodynamics. In our recent study, we have revealed that hemodynamic force is required for developing mouse hearts to grow larger in size and to develop a thicker heart tissue (myocardium). Further, we determined that the developing mouse heart is particularly sensitive to hemodynamic force, and that slightly diminishing force results in impaired heart looping and trabeculation. We aim to further understand the cellular and molecular mechanisms for how the heart responds to hemodynamic force.

III. Elucidating the signaling pathways that detect the physical force of blood flow
We currently know that blood flow creates hemodynamic force. We also know that this force shapes vessel trees into a hierarchy. However, it is unknown how the cells that make up blood vessels (called endothelial cells) sense hemodynamic force. Thus, one goal of the lab is to elucidate the signaling pathways that become activated by hemodynamic force in a process called mechanotransduction.

IV. Discovering environmental contaminants that exhibit teratogenic effects on cardiovascular development

We are exposing zebrafish embryos to environmental contaminants that have not been tested on embryos before (examples: herbicides and pesticides). The utlimate goal is to identify contaminants that are harmful to zebrafish by acting as a teratogen. A teratogen is a substance that can impair embryonic/larval development. Based on similar screens, we anticipate identifying a large percent of the contaminants with defects to cardiovascular development, and we will further test the precise manner in which the contaminants impair heart and blood vessel formation.

Information for students: Students will have an opportunity in performing research in an interdisciplinary environment, utilizing knowledge in biophysics (hemodynamics and optical imaging), developmental biology (embryo culture and manipulation), molecular biology (immunohistochemistry, PCR, western blots, gel electrophoresis, etc.), animal care and husbandry (mouse and zebrafish), and any other topic at the interest of the student.

back