"Cell Chirality in Cardiovascular Development and Disease"

CBE Department Seminar
Dr. Leo Wan
Ricketts 203, Rensselaer Polytechnic Institute
Wed, March 27, 2024 at 9:30 AM
Refreshments available in the Ricketts Coonley Lounge (120) at 9:00 a.m.

Cell chirality (handedness and left-right (LR) asymmetry) is an intrinsic capability of the cell telling left from right. Developing the vertebrate body plan with left-right asymmetry requires emerging chiral morphogenesis at multicellular levels at specific embryonic stages. Changes in the orientation of the LR axis due to genetic or environmental factors can lead to malformations and disease. However, the concept of cell chirality was never studied in detail until the recent development of novel engineering tools. We demonstrate that the cultivation of cells on micropatterned 2D surfaces and in 3D hydrogels reveals an intrinsic cellular LR asymmetry, which depends on cell phenotype and actin cytoskeleton. With these new tools, we examine the role of cell chirality on the embryonic development of cardiac LR asymmetry and the barrier function of endothelium layers. Protein Kinase C (PKC) activation reverses the inherent chirality from clockwise to counterclockwise in engineering systems.

Interestingly, activation of PKC signaling reverses the directional bias of chick cardiac C-looping. Mediating endothelial cell chirality can regulate the permeability of endothelial layers. Overall, our results strongly suggest the critical role of cell chirality in cardiovascular development and disease.

Dr. Leo Q. Wan is an associate professor in the Department of Biomedical Engineering at the Rensselaer Polytechnic Institute in Troy, NY. His research focuses on understanding physical biology in tissue development and regeneration and includes Tissue Morphogenesis, Stem Cell Mechanobiology, and Functional Tissue Engineering. He is a pioneer in cell chirality research with bioengineering platforms. His lecture titled “Why are human bodies asymmetrical?”, which was collaborated with TED-Ed, has over 1 million views. Dr. Wan received his Bachelor’s degree in Mechanics and Mechanical Engineering and his Master’s degree in Fluid Mechanics from the University of Science and Technology of China. After completing his PhD in Biomedical Engineering at Columbia University in 2007, he became a postdoctoral scientist in Stem Cells and Tissue Engineering. Leo is a Pew scholar (Class 2013) and a recipient of the NIH Director’s New Innovator Award, the National Science Foundation Early Career Award, the American Heart Association Scientist Development Grant, and the March of Dimes Basil O’Connor Starter Scholar Research Award. He is a fellow of the American Heart Association (FAHA).

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