ISCRM is thrilled to welcome two new faculty members, Min (Mia) Yang, Assistant Professor, OBGYN and Nobuhiko (Nobu) Hamazaki, PhD, Assistant Professor, OBGYN and Genome Sciences.
Exploring the Mysteries of Development and Improving Fetal and Maternal Health
As a child growing up in Chengdu, China, Min (Mia) Yang recalls her extended family being abuzz about her uncle, Xiangzhong (Jerry) Yang, the celebrated researcher who had moved to the United States in the 1980’s and become a pioneer in the field of animal cloning at the University of Connecticut and Cornell University.
“He was a brilliant scientist,” says Yang. “He was the reason I learned about reproductive cloning and somatic cell nuclear transfer (SCNT) when I was still in elementary school. He was my role model from very early on. I chose my career path at a young age because of him.”
After earning an undergraduate degree at the Sichuan Agricultural University, Yang moved to Logan, Utah to pursue a PhD in Animal Reproduction and Development at Utah State University, where she joined the lab of Irina Polejaeva. There, Yang focused on developing genetically modified large animals using SCNT that could be used in agriculture and in the study of human diseases.
During her time in Utah, Yang discovered both a love of the outdoors and a budding interest in the mysteries of the earliest stages of mammalian development. “I was drawn to the reproductive aspects of my research,” says Yang. “I wanted to know how a single cell, the egg, can so efficiently reprogram other adult cells to develop a new life. I felt a better understanding of these mechanisms could lead to more efficient cloning and this knowledge could eventually benefits for human medicine.”
That inclination to connect her research to clinical applications led Yang to undertake her first postdoc training in a lab associated with an IVF clinic in New Jersey. She studied the epigenetic profiles of human IVF produced embryos donated for research, with a goal to discover biomarkers indicative of embryo quality.
However, she soon realized that patient sample-based research presented limitations, both in terms of resources and ethical concerns. Motivated to delve deeper into the fundamentals of embryonic development, she joined Ali Brivanlou’s synthetic embryology lab at Rockefeller University in New York City. There, she leveraged quantitative stem cell models to explore the molecular and cellular basis of early human development.
Now, as Yang launches her own lab at the University of Washington, she is carrying that emphasis on translational science forward.
“I am a basic scientist. But I want my research to have a translational perspective. “My hope for my lab is to use advanced stem cell models and animal models to study the conditions that impact reproductive and maternal fetal health.”
Yang cites one investigation in which her lab will explore how chromosomal abnormalities impair normal development and cause miscarriages using both human embryonic stem cell and non-human primate models.”
Additionally, Yang and her team will utilize advanced 3D stem cell models to gain fresh insights into essential embryonic processes, particularly gastrulation and placentation. According to Yang, these cell-based models could serve as valuable tools for investigating specific conditions like hormone imbalances and preeclampsia, which can complicate pregnancies and are generally challenging to study.
Progress on these fronts could have important implications for medicine and for women in general, says Yang. “I believe improving female reproductive health will promote gender equality. Women have a limited time window for reproduction. If we have more control over this clock, and if we can find ways to lower gestational risks and boost pregnancy success rates, that could help women who are also pursuing careers, for example.”
In addition to her appointment in the UW Medicine Department of Obstetrics & Gynecology, Yang will also be a faculty member in the Institute for Stem Cell and Regenerative Medicine (ISCRM), an affiliation that places Yang in a community of like-minded researchers.
“Being a part of ISCRM is an opportunity to meet potential collaborators to learn new techniques from my colleagues,” says Yang. “The combination of that and the access to clinical resources in my department is what makes this position really special.”
Studying the Seed of Life
One ISCRM colleague Yang expects to team up with is Nobuhiko (Nobu) Hamazaki, PhD, who is also joining UW Medicine this month. Like Yang, Hamazaki has also studied the origins of life in a non-human species. In his case, however, it was a much smaller animal – the sea urchin.
When he was a high school student in Kanazawa, on the west coast of Japan, Hamazaki and his classmates extracted sperm and eggs from male and female sea urchins, fertilized them in vitro, then watched the cells multiply under the microscope. “That experiment led to my current research direction,” says Hamazaki.
Later, as an undergraduate student at Hokkaido University, Hamazaki became intrigued by a question that continues to shape his career. “I saw that the earliest stages of development in sea urchins and humans were quite similar, and I wondered about the genetic processes that could produce such different organisms.”
At Kyoto University, Hamazaki earned a PhD analyzing the mechanisms of fertilization and gene activation and exploring the regulation of genes involved in early development. His next step was a postdoctoral position at Kyushu University, where he contributed to a system to model how oocytes differentiate from stem cells, eventually identifying eight genes that are essential for that transformation.
Hamazaki has remained interested in oocytes, the ovarian cells he refers to as the seed of life.
“While fertilization is a critical step, oocytes are central to a process by which small cells become larger cells. But this process is not well understood. For example, how do oocyte, which is a huge cell, coordinate gene expression in such a huge amount of space in nuclear?”
In 2019, Hamazaki moved to Seattle to join the lab of ISCRM faculty member Jay Shendure, MD., PhD. There, he turned his attention to the genetics at work after fertilization, applying stem cell-based methods capable of generating embryo-like structures with cutting-edge genomics technologies that allowed the team to investigate the function of genes involved in human development.
Hamazaki imagines a future when it might be possible to differentiate stem cells into oocytes in the lab, opening the door to a possible treatment for infertility. For now, he is looking forward to partnering with other stem cell researchers who share his taste for collaboration and collective problem solving.
“I have a passion for applying basic science,” says Hamazaki. “It’s interesting and it’s important for human medicine. In the stem cell field, there is a possibility to help people. If we understand the fundamentals of normal development, we’ll know more about what makes it go wrong.”