Every day, 20 people die waiting for an organ transplant. Kyle Loh would like to see that number reduced to zero. For his groundbreaking PhD work mapping out the developmental pathways that stem cells take on their way to becoming various organs and tissues, Hertz Fellow Kyle Loh has been awarded the Fannie and John Hertz Foundation’s 2018 Thesis Prize. Granted annually since 1981, the thesis prize recognizes one Hertz Fellow’s dissertation for overall excellence and pertinence to high-impact science. Each Thesis Prize winner receives an honorarium of $5000.
Imagine if, instead of waiting years for a donor with a genetic match, patients in need of a transplant could have a replacement “organ” grown in the lab. This promise has motivated decades of research into stem cells, cells that can grow and differentiate into every other kind of cell in our body, but controlling the cells’ development enough to build new biological tissue has been an elusive goal.
Until Kyle Loh, that is. When Loh was awarded a Hertz Fellowship in 2011 to take a PhD in developmental biology at Stanford University, he was already leading a research team at the Genome Institute of Singapore, at the young age of 17. His research only advanced from there. In Irv Weismann’s lab at Stanford, Loh provided a new way forward for regenerative medicine, bringing the use of stem cells for tissue repair and organ replacement that much closer to reality.
For his PhD thesis, titled A Developmental Roadmap for the Diversification of Human Tissue fates from Pluripotent Cells, Loh mapped out the chemical signals that drive stem cells to develop into different tissues.
Then, he solved a problem that had long plagued regenerative medicine.
When stem cells differentiate during our own development from a baby into a human being, a given cell’s descendants will naturally develop into a diverse group of different cell types. However, to grow individual organs or types of cells in a dish for regenerative medicine, it’s much more useful to have pure populations of a given stem cell type. With the developmental roadmap in hand, Loh showed how to induce and suppress the right chemical signals to produce pure populations of cells for growing liver tissue, pancreas tissue, and more.
These pure populations of cells are not quite organ replacements – they still must be assembled into a form that will function in the body, and transplanted in a way that doesn’t trigger a dangerous immunological reaction. But in some cases, extensive knowledge of the “developmental roadmap” may allow doctors to skip the replacement step altogether. Since his graduation, Loh and his collaborators have discovered and produced a “multipotent” lung stem cell, which develops into both types of lung tissue, the airways that carry air through the lungs and the alveoli that pass it to our blood. When the multipotent lung cells were injected into injured mouse lungs, they developed into both types of tissue, healing the lung without transplant.
Loh’s work is far from done. Now an assistant professor of Developmental Biology at Stanford, and as part of the Stanford Institute for Stem Cell Biology and Regenerative Medicine, he continues his work to understand the immunological interactions that determine whether an organ replacement will be rejected. And connections within the Hertz community are helping take his work in new directions.
With Hertz Fellow and housemate Will Allen, a PhD candidate in neuroscience at Stanford, Loh is now working to map out how different types of neurons and other cells develop from stem cells. The research will provide new insight into how our brains form and provide important insight into the diseases that occur when this development goes awry.
“Being part of the Hertz family has been a wonderful experience for me,” he said. “The tight-knit community of the in-school fellows has given me a fantastic experience and I hope to continue cultivating these relationships and connections between fellows. “
Since 1963, the Fannie and John Hertz Foundation has been providing PhD Fellowships to exceptionally talented individuals expected to have the greatest impact on the application of science, math and engineering to human problems. It is the legacy of John Hertz, a Hungarian immigrant who made his fortune by capitalizing on the entrepreneurship prospects in the budding automotive industry, and who strongly believed that innovative and entrepreneurial solutions were vital to the strength, security and prosperity of our nation. For more information on the Hertz Foundation and the cutting-edge innovations led by our Hertz Fellows please visit www.hertzfoundation.org.