Faculty Highlight: Leo Wan

Do cells lean left or right?

BME Faculty Highlights Series
Associate Professor Leo Wan and the Laboratory for Tissue Engineering and Morphogenesis

This article is the first in a series aimed at spotlighting the faculty in the Department of Biomedical Engineering at RPI. In this series, we will highlight biomedical research areas, cutting edge engineering techniques, student and trainee successes, as well as the broader societal impacts of the work in BME. Stay tuned each month of this academic year for more features, and follow us on Twitter @RPI_BME (https://twitter.com/RPI_BME).

Cells, just like the humans they make up, can be left- or right-handed, thanks to an inherent cell property called chirality. Drugs or other environmental factors can alter the chirality of cells during fetal development, leading to drastic changes in growth and development and resulting in life-altering birth defects. BME Associate Professor Leo Wan's group at RPI is therefore looking to develop fast, easy-to-use tests to identify and learn more about the factors that can lead to these changes in cell chirality.

Principal Investigator Leo Wan explains his discovery that chirality can easily be observed in cells grown on 2D micro-patterned surfaces or self-assembled in 3D within hydrogels. Growing and observing cells in the laboratory is faster, cheaper, and often more versatile than running experiments in animals. In drug development, determining whether a drug may lead to chirality problems often involves animal testing. However, ethical concerns with animals, differences between laboratory animals and humans, and costs in time and resources are all great reasons for the Wan lab to pursue a “cells on a chip” approach.

Graduate student, Jennifer Rico-Varela, is using this 3D cellular self-assembly to measure the “effect of small molecules and pharmaceutical drugs” on cell chirality during embryonic development. For this work, she uses human embryonic stem cells, which behave similarly to cells “during the first trimester of pregnancy” and can therefore provide insights into whether a drug could cause organs to develop in the wrong direction. Rico-Varela hopes that her research will contribute to “new insights and high-throughput screening platforms into the study of human laterality disorders or birth defects.”

In addition to working on the patent-pending 2D and 3D technologies to screen cell chirality for drug side effects, the Wan lab uses their cells on a chip platform to study the basic behavior of cells. Ultimately, the understanding of the basic mechanisms that direct cell chirality can be used to detect and prevent future birth defects. This knowledge of how to manipulate the directionality of cell growth and development could also lead to advances in tissue engineering, where control of the production of tubal structures, such as blood vessels and gastrointestinal tract, could be vital to designing functional tissues and organs in the laboratory.

Because mice and other animal models may not necessarily predict the behavior of human cells, Katie Worley, another BME graduate student in Wan’s laboratory, is exploring the possibility of studying cell chirality and left-right asymmetry in the “in vitro differentiation of human embryonic stem cells” using the lab’s 3D hydrogel system. Just like their response to some drugs, cell behavior and organ development in animals may not necessarily have the same left-right characteristics as in humans. “I’ve always been interested in human development,” Worley adds, “and I was excited to be able to work on a project that might allow for a more human focused approach to studying embryonic development.”

This cutting edge research hasn’t gone unnoticed. Since he’s joined RPI, Wan and his group’s research have been awarded the NSF CAREER Award, NIH Director’s New Innovators Award, and the Pew Biomedical Scholar award, among other grants and awards. You can learn more about chirality and its role in disease from Wan’s video through TED-Ed (https://www.youtube.com/watch?v=hLgh1pJP5ng&feature=youtu.be) and in his contribution to a feature on Wired (https://www.wired.com/2017/02/body-can-tell-left-right/). Meanwhile, Wan looks towards the future, when he foresees that their patent-pending 2D and 3D assays will be powerful tools to screen for and ultimately prevent them.