When we think about forces that drive progress in biomedical research, we often point to technology, collaboration, public investment, and private philanthropy. More than ever, we also appreciate the role that all forms of diversity play in our work. In order to solve the biggest problems in medicine, we must be shaped by the broadest possible spectrum of perspectives, representing a global mosaic of cultures, ethnicities, values, and scientific disciplines. We are grateful to everyone within the institute who embodies that spirit of unity and to our donors who have helped us become a world leader in regenerative medicine.
Chuck Murry, Director | Hannele Ruohola-Baker, Associate Director | Jen Davis, Associate Director | Nate Sniadecki, Associate Director
Tapping into Our Regenerative Potential
ISCRM researchers in more than 130 labs are learning to control the machinery that causes our cells to replicate. This is the basis of regenerative medicine. If we can replenish lost cells – or slow the growth of unwanted cells – we can address the root causes of diseases, and improve wellbeing for billions of people.
- At the same time, investigators at ISCRM are working together to answer another tantalizing question: Why are some animals able to regrow bony appendages, such as limbs, after amputation – and could something in the biology of these animals teach us to someday regenerate human limbs?
- In September, researchers led by Ronald Young Kwon, PhD partnered with the Brotman Baty Institute to sequence thousands of zebrafish genes and identified a two-way cellular differentiation process that helps the aquatic creatures, which share 70% of their genes with humans, regenerate fins.
The sequencing work was supported by an NIH grant that Kwon shares with ISCRM colleagues Olivia Bermingham-McDonogh, PhD, Tom Reh, PhD, Andrea Wills, PhD, and Hannele Ruohola-Baker, PhD. This collaborative, known as the Regeneration Club, studies regeneration across species, organs, and tissues in hopes of unlocking regenerative potential in humans.
Did you know? Philanthropy supports preliminary research that leads to millions of dollars in federal grants.
Collaborating Against Cancer
With funding from the National Cancer Institute, Thelma Escobar, PhD and Sergei Doulatov, PhD are teaming up to explore the molecular origins of AML, a family of blood cancers that claim more than 22,000 lives annually. The ISCRM peers hope that by combining their backgrounds in hematology and chromatin biochemistry they can produce insights with clinical significance for oncologists and patients.
(Chromatin is the raw material that the body uses to build chromosomes, which carry our DNA. Modifications that occur to our DNA during our lifetimes are known as epigenetic changes – and the full set of those changes is known as the epigenome.)
The researchers will use mouse and human induced pluripotent stem cell (iPSC) models to study the interplay of the protein NPM1 and the epigenome and to learn more about what goes awry as blood stem cells with the mutation divide and eventually cause illness.
“What we have found could someday be very useful in a clinical setting. Our research shows that once directed to a specific site, the computer designed epigenomic binder successfully upregulates gene expression, leading to the desired changes in cell function. Best of all, this is an organic approach in which careful human intervention nudges cells to follow their natural instincts.” – Shiri Levy, PhD
Regulating Epigenetics and Regenerating Teeth
Scientists in the Ruohola-Baker Lab and their counterparts in the UW Institute for Protein Design (IPD) are combining stem cell biology and designed protein technology to test and develop root-cause interventions that could give physicians entirely new ways to treat cancer, COVID-19, heart disease, Alzheimer’s disease, strokes, and other conditions. Here are two recent examples of collaboration between ISCRM and IPD.
Stem cell biologists are learning to regulate how cells differentiate. Shiri Levy, an Acting Instructor in the Ruohola-Baker Lab, has led the development of a computer-designed protein binder, engineered with IPD scientists, that is capable of selectively controlling an epigenetic regulator that influences cell fate across multiple stages of development.
In another collaboration with IPD, ISCRM researchers used designed protein mini-binders to supercharge a pathway that gives rise to odontoblasts, specialized cells that play a crucial role in tooth development. The ability to produce different types of dental tissues in the lab marks a step forward for regenerative dentistry.
Did you know? Philanthropy allows multidisciplinary partnerships to become innovation multipliers.
“We are exploring the basic tenets of fibroblast biology. We’re learning which genes are necessary for cells to transition and what causes a fibroblast to awaken and become activated. The implications are definitely exciting.” – Darrian Bugg, PhD (Davis Lab)
Healing Hearts
Every year, more than 1.5 million Americans suffer a stroke or a heart attack. For survivors, these events can lead to significantly diminished quality of life. ISCRM researchers use a multidisciplinary approach to produce discoveries that could someday help people around the world recover from strokes and heart attacks.
- Mike Regnier, PhD has received a $3.3 million NIH grant that will help the Center for Translational Muscle Research and the Murry Lab translate discoveries about the mechanics of heart contractions into new ways to help heart attack patients.
- Jen Davis, PhD and Darrian Bugg, PhD are authors of a February 2022 study that reveals illuminating details about the role an RNA binding protein (MBNL1) plays in the steps that lead to scarring. Controlling scarring could lead to better recovery for heart attack victims, more effective wound healing, and better outcomes for patients with certain forms of liver and lung diseases.
- With a five-year, $2.9 million grant from the National Heart, Lung, and Blood Institute, Patrick Boyle, PhD and his partners in the Department of Medicine and Department of Mechanical Engineering will harness advances in clinical imaging artificial intelligence, computational physiology biology, and multi-physics mathematical modeling stem cell technology to help doctors more effectively predict and treat ischemic strokes and understand their complex relationships to underlying cardiovascular disease.
Building a More Inclusive Community
We are pleased to share these stories of progress within the ISCRM community that reflect our ongoing work to create a more diverse research environment.
- Students from across the country took part in the ISCRM Undergraduate Summer Program, which provides paid lab work, training in professional skills, and opportunities to connect with other students from around the world.
- Undergraduate researcher Dessirée Ortaç and PhD students Jordan Jackson and Susana Simmonds Bohorquez received the inaugural ISCRM DEI Service Awards in recognition of their contributions to the effort to increase diversity, equity, and inclusion across the institute.
- A $431,000 NIH grant will allow a team led by Ronald Young Kwon, PhD to foster the early careers of young scientists from underrepresented backgrounds through a formal mentor network that includes Tam’ra-Kay Francis, PhD, Arianna Gómez, PhD, Jyoti Rai, MS, Joyce Tang, MS, and Howard Chansky, MD.
Did you know? Philanthropy benefits human health by propelling discoveries from the lab to the clinic.
Quick-Hit Highlights from 2022
Credit: Benjamin Freedman
Exploring the Role of Cilia in Polycystic Kidney Disease
Research from Beno Freedman, PhD and Hongxia Fu, PhD, supported in part by an ISCRM Innovation Pilot Award, explored the role of cilia in cell signaling, differentiation, and disease development. In the investigation, the researchers engineered induced pluripotent stem cell lines incapable of forming cilia, revealing how these hair-like organelles can contribute to polycystic kidney disease (PKD) and how they interact with the hedgehog signaling pathway to promote organ development.
Developing a Neuromuscular Modeling System
In the Neuromuscular Disease Research Group, Alec Smith, PhD, David Mack, PhD and Mark Bothwell, PhD are working together to engineer a system to explore connections between neurons and muscle tissue in a way that closely models neuromuscular junction function in the body. This technology, based on a tool designed by Nate Sniadecki, PhD will enable more precise modeling of neuromuscular diseases.
Improving Treatments for Hemophilia A
In a longitudinal study funded by the NIH, a team of researchers led by Jill Johnsen, MD will trace the roots of risk for immune complications associated with a common treatment for Hemophilia A starting from the time in the womb. The data will help scientists and physicians to better predict a patient’s risk and develop individualized treatment plans to mitigate the immune response.
Chehalis STEM Camp
In August, more than 45 ISCRM faculty, students, and staff traveled to Chehalis, Washington to lead two days of a UW STEM camp offered to more than 50 Lewis County high school students. The first day featured interactive experiences focused on organs and systems, including the heart, brain, and lungs, kidney chips and organoids, blood vessels, the neuromuscular system, and the pancreas. On the second day, students explored biotechnology topics, including CRISPR gene-editing, epigenetics, zebrafish, computational medicine, biomaterials, and measuring cardiac force. We were also honored to welcome Sen. John Braun, Rep. Peter Abbarno and Rep. Ed Orcutt, who joined us on the first afternoon.
Recruiting Rising Stars
By partnering with the UW Department of Orthopaedics and Sports Medicine, the Department of Obstetrics & Gynecology, and the Department of Genome Sciences, ISCRM was able to recruit four talented rising-star researchers who will bring highly-sought expertise in digit regeneration, developmental biology, and women’s reproductive health, elevating the UW’s impact in these crucial areas of research.
Thank you!
We are grateful to the generous supporters who have helped ISCRM become an engine of discovery in the field of regenerative medicine. If you’d like to learn more about how philanthropic investments fuel our work, please contact Jeannie Stuyvesant, senior director for philanthropy, at jstuy@uw.edu.