Yu Jung Shin has always been fascinated by disease modeling. As a young scientist from Seoul, she was drawn to the United States by opportunities to learn the art of recreating diseases in the lab to study how they begin and how to stop them. New technologies have made disease modeling faster and more precise than ever and are helping researchers pursue treatments for many common and deadly disorders that impact people of all ages worldwide. After earning an undergraduate degree at Johns Hopkins University, Shin found a home in the Zheng Lab in the Institute for Stem Cell and Regenerative Medicine (ISCRM).
“I found my niche in stem cell modeling of the human organ system,” says Shin, who is now a fourth-year graduate student. “My goal is to use all the skills I’ve gained to model systems on a micro-physiological scale. I ended up focusing on vasculature because it goes everywhere.”
Shin works with disease modeling tools known as organoids, tiny three-dimensional structures grown in dishes from self-assembling cells. At ISCRM and elsewhere, organoids are used to study the kidneys, brain, and liver, and other organs. Shin uses vascular organoids for modeling organ-specific vasculature that can resemble real human blood vessels. She hopes to investigate what role various cell types, pressure, and flow play in the development of organ-specific vasculature and wants to utilize this tool to understand what parameters are altered in disease models.
Together with her mentor ISCRM faculty Ying Zheng, PhD, an Associate Professor in Bioengineering, Shin is asking big questions that could push the boundaries of biomedical research. Finding answers to these questions takes ingenuity, perseverance, lots of data, and funding. An ISCRM fellowship she received in 2020 provides unique support for her as an international student. This fellowship has helped her to work with others in her lab to receive an R21 grant shared by the Zheng and Young labs.
Emily Olszewski is also a graduate student in an ISCRM lab. Originally from Wisconsin, Olszewski studies how fibroblasts impact blood vessels in the heart, part of a larger effort to understand and control scarring – and hopefully – improve outcomes for patients at risk for heart failure. Like many other graduate students, Olszewski needs funding to finish her research, yet can’t finish her research if she is constantly focused on grant and fellowship applications – one reason she was grateful to receive an ISCRM fellowship in 2019.
The fact that Shin and Olszewski have produced groundbreaking research published in high-impact journals and are on track to earn PhDs within the next year is a testament to individual determination backed by a fellowship program that has helped propel the careers of more than 60 young scientists.
The ISCRM Fellows program began in 2017, the year the Washington State Legislature first included funding for ISCRM in the state budget. In a critical show of support for stem cell research, the legislature appropriated $2.25 million for core staff and technologies, innovation pilot awards for faculty, and a trainee fellowship program to help the UW fulfill its mission, increase capacity for labs, and provide foundational research experiences for graduate, undergraduate, and postdoctoral students embarking on science careers. In 2019, the annual funding was increased to $2,625,000.
Since 2017, ISCRM fellows representing 28 labs across 13 departments have been listed on more than 60 published papers and have advanced research on more than 20 diseases. Research topics have included protein design, 3D tissue engineering, disease modeling, aging, epigenetics, regenerative medicine, immunology, bioinformatics, high-throughput genomics, drug development, gene regulation, organoids, and stem cell biology. Among past fellows, 84% say the program positively influenced their ability or desire to study or research at the University of Washington.
ISCRM fellows have represented countries and cultures from all over the world, a vital contribution for an institute that recently established a five-year strategic plan for equity and inclusion.
“Young scientists from diverse backgrounds bring passion, creativity, and fresh perspectives to our labs,” says Hannele Ruohola-Baker, PhD, a Professor of Biochemistry, Associate Director of ISCRM, and Director of the ISCRM Fellows Program. “What they don’t always have is the financial means to be full-time researchers. The ISCRM Fellows Program allows them to maximize their time in the lab and really commit to the projects. The payoff for them, for their labs, and for society is huge.”
David Mack, PhD is an Associate Professor of Rehabilitation Medicine. He oversees the award program at the undergraduate level. Mack echoes the value of the ISCRM Fellows Program to the broader community. “We have trainees at every level, from undergraduates to postdocs, making pivotal contributions to research projects that could help actual patients suffering from heart disease, cancer, muscular dystrophy, and other devastating conditions. This is how science turns into medicine. It’s very exciting.”
Fred Yeboah is one recent ISCRM Fellow whose funded research project is helping to bring the world closer to an urgently needed treatment for an incurable disease. Yeboah, who is from Ghana, is a graduate in the lab of Jessica Young, PhD, an Assistant Professor of Laboratory Medicine and Pathology. Young and her lab use stem cells derived from Alzheimer’s disease patients to study how the disorder begins.
For the last two years, funding from consecutive ISCRM fellowships has enabled Yeboah to focus his attention on the means by which a protein known as HDAC2 inhibits other genes responsible for memory formation when it is overexpressed in the brain. In partnership with the Ruohola-Baker Lab and former ISCRM faculty member Yuliang Wang, Yeboah has gathered data that was the basis for a paper published this spring in the International Journal of Molecular Sciences.
While Yeboah was producing insights that are contributing to the field of Alzheimer’s disease research, he took advantage of other opportunities made possible by his fellowship. He participated in the Cascadia Corridor Research Symposium and won third prize for his poster. He was awarded the University of Washington Retirement Association UWRA Patricia Dougherty Fellowship in Aging. And he is preparing to publish another paper based on his thesis.
“Especially as an international student, this fellowship has meant a lot for my professional development,” says Yeboah. “I’ve had opportunities to spend more time in the lab and to collaborate with other labs. The findings are good for the field and I’m excited about how the lab is contributing to Alzheimer’s research.”
Sometimes an ISCRM fellowship can lead to a longer-term engagement. As an undergraduate student, Kira Evitts received an ISCRM fellowship that allowed her to research in the Young Lab, where she learned to differentiate stem cells into neurons that could be used in the study of Alzheimer’s disease. Three years later Evitts is a graduate student doing organoid work with the Young Lab and vascular engineering in the Zheng Lab. “The chance to have a full-time summer job in the lab was really essential and made me realize that I wanted to continue studying the brain,” says Evitts.
Shin, Olszewski, and Yeboah are each preparing to complete PhD projects in the near future. Shin hopes to begin a postdoc and perhaps someday lead her own lab centered on disease modeling. Yeboah has plans to continue his research in a commercial setting perhaps at a pharmaceutical company.
For her part, Olszewski, who leveraged her fellowship into a prestigious NIH F31 grant, is considering fellowships that will allow her to explore the intersection of science and education policy. “Grad school has taught me that I love doing science and I love mentoring. I want to find a role that allow me to use those skills even if it isn’t on the traditional academic route.”
Nisa Williams earned her PhD in 2020 after years of research embedded in cardiovascular biology. In her project, Williams created sophisticated 3D models of the heart that allowed her study the intricate folding and remodeling that drives cardiac development at the cellular level. The premise is that understanding how the heart grows in the lab will help scientists heal injured hearts in the clinic.
The ISCRM Fellows Program allowed Williams to finish her thesis, often working in isolation during the COVID-19 pandemic – a hardship that made her even more appreciative of the research community around her. “The fellowship helped me build a network of scientists who have backgrounds in so many different areas and who were able to give me so much one-on-one time and feedback on my research. They also helped me pursue my career goals beyond the university.”
As it happened, those career goals dovetailed with the research Williams conducted as an ISCRM fellow.
Williams, who received her degree in Bioengineering, was mentored by ISCRM Director Chuck Murry. Over the last few years, Murry and his team at UW have demonstrated the viability of regenerating the human heart using cardiomyocytes derived from stem cells. Murry, as a Senior Vice President and Head of Cardiometabolic Cell Therapy at Sana Biotechnology, is working to shepherd heart regeneration toward human clinical trials at Sana with the use of certain technologies developed at UW.
In an unusually seamless transition from graduate school to the real world, Williams is now a member of the Cardiac Cell Therapy team at Sana, where she is helping to translate aspects her thesis project into therapies that could help patients. “I feel very lucky to work for a company that is turning research I’ve been a part of into potential treatments. I’m also leading projects that are outside of my core experience, which has been fun and challenging as well.”
Eligibility for the ISCRM Fellows Program is not limited to the Seattle campus. Students from UW Bothell have also been able to contribute to research in ISCRM labs thanks to fellowship funding. This summer, three undergraduate students helped advance ongoing investigations related to osteoporosis, heart regeneration, and polycystic kidney disease.
Prabhat Aluri, a Math major from UW Bothell, spent the summer in the Kwon Lab, where he was exposed to many of the same research approaches he’d been introduced to in class. “I had the opportunity to witness methods of genetic research that I have studied extensively through coursework but have not had the chance to experience, such as CRISPR Cas9 genetic editing,” says Aluri. “And I now have useable data that is ready to be analyzed in further studies.”
“Exposing UW Bothell students to the culture of ISCRM labs is invigorating and transformative, says Bryan White, PhD, a Senior Lecturer at UW Bothell. “It is almost unthinkable that my students get to participate in stem cell science at this level.”
White notes that the program’s emphasis on increasing diversity has particular meaning for UW Bothell. “Twenty percent of our students are from a traditionally underrepresented ethnic group and 50% of students will be the first in their family to receive a four-year degree. Training marginalized students and helping them realize that they can do science in a stem cell lab is transformative for them and beneficial for society.”