Dr. Min (Mia) Yang has received an NIH Director’s New Innovator Award that will enable her lab to recreate key aspects of early embryonic development and, hopefully, point the field toward new ways to improve maternal health, enhance fertility treatments, control unwanted cell growth, and harness the body’s natural capacity for regeneration.
Dr. Min (Mia) Yang is a University of Washington Assistant Professor of Obstetrics & Gynecology and a faculty member in the Institute for Stem Cell and Regenerative Medicine. Her laboratory is interested in the processes that drive – and disrupt – human development in its very earliest stages.
Her team uses human pluripotent stem cell (hPSC) models to unravel mysteries at work in fertilization, implantation, and the initial phases of embryogenesis. The questions the Yang Lab is attempting to answer have profound implications for reproductive biology, cancer treatment, and regenerative medicine.
One area of focus for the Yang Lab relates to chromosomal instability in early development. Chromosomes carry the instructions that guide how cells grow. Too many or two few chromosomes in a cell, a condition known as aneuploidy, can cause problems during development or later in life. However, embryos can be remarkably resilient and are capable of cleaning up the cells with chromosomal mistakes.
In previous research, published in Nature Communications, Yang and her lab used stem cells to model the placental environment. They found that chromosomal errors in the embryo are quite common, even necessary for development in some cases, and also uncovered biological pathways – built-in quality control mechanisms – that help abnormal cells survive.
An intriguing revelation from their research suggests that tolerance for chromosomal abnormality is connected to cell fate. The Yang Lab has discovered in recent years that aneuploid cells are actively eliminated from the embryonic lineage that will form the fetus but seem to have a predisposition to become the trophectoderm cells that give rise to highly resilient placental cells. All of this happens in a “fitness-switching” window in early embryogenesis.
Nonetheless, how different cell types cope with chromosomal instability, which genes and signals are involved, and how cells compete with each other for survival all remain poorly understood.
“We can see that the embryogenesis process is very error-prone,” says Dr. Yang. “But we are still learning why that is. Closer study of the means by which cells adapt to, or are eliminated by, chromosomal instability using advanced modeling techniques could have exciting research and even therapeutic impacts that extend well beyond developmental biology.”
Now, those efforts to shed light on the cellular drama unfolding during that narrow, but formative window of time have drawn significant new funding. Dr. Yang has received an NIH Director’s New Innovator Award through the institute’s High-Risk, High-Reward Research program, an initiative that supports exceptionally creative scientists pursuing highly innovative research with the potential for broad impact in biomedical, behavioral, or social sciences.
Funding – totaling $1.5 million over five years – will enable Yang and her lab to recreate key aspects of early embryonic development and, hopefully, point the field toward new ways to improve maternal health, enhance fertility treatments, control unwanted cell growth, and harness the body’s natural capacity for regeneration.
The investigators believe the grant will help them close a major research gap. While chromosomal instability has been studied in cancer, there has been less examination of the phenomenon in the early embryo, partly due to a lack of suitable modeling tools. The Yang Lab’s access to hPSC, genomics, and imaging technologies will allow them to watch a “survival of the fittest” process play out as cells with different numbers of chromosomes duel for dominance and are ultimately selected for various fates – in other words, which cell type in the embryo they will become, if they survive.
“We think is a very interesting and important question to study,” says Dr. Yang. “What we learn will help us to understand cell lineage and to explain why harmful cells win out against healthy cells in cancer. It will teach us how to optimize cells used in cell therapies. It will help the field improve assisted fertility treatments. And it will establish new methodologies that could be broadly applicable to any area of study that involves chromosomal instability.”