Masked and mindful of the challenges before us, we have returned to the lab to continue confronting the root causes of disease through collaboration and innovation. We are proud that researchers at all career levels and from so many scientific and cultural backgrounds have made pivotal contributions to discoveries that are closer than ever to the clinic – and yet we know we have much more to do to achieve our full potential as an institute. We thank all those who have supported ISCRM and hope you will enjoy this report on the progress you have made possible.
Chuck Murry, Director | Hannele Ruohola-Baker, Associate Director | Jen Davis, Associate Director | Nate Sniadecki, Associate Director
Heart Regeneration
In a period of extraordinary health challenges, heart disease remains the leading cause of death in the world. More than 650,000 Americans lost their lives to heart disease in 2020. ISCRM researchers are pursuing new treatments that could soon help suffering patients recover more completely from heart injuries. Two recent breakthroughs in particular point to a brighter outlook in the near future.
In September, a research team led by ISCRM Director Chuck Murry, MD, PhD used a large animal model to demonstrate the use of FDA-approved drugs to control arrhythmias (irregular heartbeats) that have been a hurdle in the effort to bring heart regeneration closer to the clinic. The results of the study indicate that pharmacological treatment of engraftment arrhythmia may be a viable strategy to improve safety and allow further clinical development of cardiac remuscularization therapy.
Another piece of the heart regeneration puzzle fell into place this year when ISCRM faculty members Jen Davis, PhD and Nate Sniadecki, PhD used rainbow reporter technology to show conclusively that transplanted heart cells do proliferate in vivo, a finding that could help researchers improve the efficacy of cell treatments for heart disease and other conditions.
Donations Matter! Generous support from Lynn and Mike Garvey has fueled heart regeneration research at ISCRM and has helped keep this life-saving treatment for heart disease on track to be in human clinical trials as soon as 2023.
Diversity, Equity, Inclusion
At ISCRM, we are bound by a belief that public health and human rights are inseparable. We are at our best as a research community when scientists representing different backgrounds, cultures, and worldviews work together to solve complex problems. We are pleased to report that we have developed a measurable five-year strategic plan for equity and inclusion to guide our commitment to antiracism and social equality, and to creating a more equitable, inclusive, and welcoming environment.
This summer, three students from Oregon, Washington State, and Cameroon joined ISCRM labs as part of a Research Experience for Undergraduates (REU) program that aims to increase access to real-world research opportunities. Susana Bohorquez, who first came to UW as an REU student from Texas, is now pursuing her PhD in the Stevens Lab.
ISCRM faculty member Kelly Stevens, PhD is the lead and co-corresponding author of a paper calling on the National Institutes of Health and other funding agencies to address disparities in allocating support to Black researchers.
Donations Matter! ISCRM has plans to grow the REU program over the next several years. Contributions from donors will help us provide stipends and housing for REU participants.
Protein design allows us to use what nature has provided and takes it a step farther. Our bodies make antibodies to fight antigens. Here we make antibodies work better through the use of small, designed, self-assembling proteins that contribute to more effective regeneration and greater potency against cancer. – Hannele Ruohola-Baker, PhD
Designed Regeneration
Scientists in the Ruohola-Baker Lab and their counterparts in the Institute for Protein Design 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 COVID-19, heart disease, Alzheimer’s disease, strokes, and other conditions.
In just one example of designed regeneration, ISCRM faculty members Hannele Ruohola-Baker, PhD and Beno Freedman, PhD are co-PIs on a $3.4 million Department of Defense grant that is allowing ISCRM and IPD scientists to design and test synthetic protein scaffolds built to regulate biological pathways crucial for healthy blood vessels.
Donations Matter! An anonymous donation of $580K is allowing stem cell experts at ISCRM to play a critical role in a partnership with IPD that could result in faster, more accurate, and less expensive treatments for a wide range of diseases.
Cancer
Most diseases studied by ISCRM researchers are caused by cell depletion. In cancer, the problem is too much cell growth. One central aim at ISCRM is to understand how to regulate natural mechanisms to accelerate the death of unwanted cells while sparing healthy cells. Stem cells and designed protein technology are two of the tools that are helping in the fight against cancer.
ISCRM faculty member Julie Mathieu, PhD is partnering with colleagues at the Institute for Protein Design and Fred Hutchinson Cancer Center to test a hunch that more precise regulation of a signaling pathway known as TRAIL could lead to better outcomes for cancer patients.
In the Ruohola-Baker Lab, more than 50 undergraduate students have contributed to a multiyear effort to use fruit flies and breast cancer organoids to screen for potential new cancer drugs and to identify a druggable pathway that could be a target for future cancer treatments.
When it comes to drugs and dementia, we often don’t know if the increased risk of dementia is due to the underlying condition that the drug is treating or if it is due to the direct action of the drug. By treating stem cell-derived neurons from this clinically characterized population with dementia, we can tease this out. – Jessica Young, PhD
Alzheimer’s Disease
Over the last several years, ISCRM faculty member Jessica Young, PhD has partnered with leaders of the UW Alzheimer’s Disease Research Center and the Kaiser Adult Changes in Thought study (ACT). Over the last three decades, the study has enrolled more than 5,800 older patients, who are then tracked as they age, revealing insights about brain health and about risk and resilience factors related to neurodegenerative diseases like Alzheimer’s.
This year, the ACT Study received a $56 million grant from the National Institute on Aging. In one collaboration supported by the grant, Young and Dr. Shelly Gray from the School of Pharmacy are investigating how commonly prescribed classes of medications relate to the incidence of dementia. Young is using stem cells derived from deceased patients with dementia to understand how these drugs could impair neuronal function that would lead to neurodegeneration.
Donations Matter! The more we know about the genes involved in a disease, the better we can diagnose and treat patients. Generous support from Larry and Eileen Tietze allowed ISCRM to launch a new Genomics Core. Additional support will help provide the expert staff and cutting-edge equipment researchers like Jessica Young need to translate genetic insights into powerful new diagnostic tools and treatments that address the root causes of disease.
Quick-Hit Highlights from 2021
Kidney Chips in Space
In June, an unmanned rocket bound for the International Space Station carried 24 credit card-sized chips containing living kidney cells. The mission was part of an effort to study the formation of kidney stones in microgravity. ISCRM faculty member Ed Kelly, PhD and doctoral student Kendan Jones-Isaac are playing leading roles in this research. Undergraduate researcher Mickey Ruiz helped prepare the experiments and designed the mission patch (see right). Ruiz, a senior majoring in physiology, is a Costco Scholar, and a leader of FEEDBACK, an initiative that fosters intellectual curiosity in middle school students from low-income communities and aims to increase diversity in STEM fields.
Prestigious Award for Kelly Stevens
Congratulations to ISCRM faculty member Kelly Stevens, PhD, who received a $1M grant from the Keck Foundation that will fund a three-year effort to shed light on the role of mechanical factors in liver regeneration.
The Muscle Center Turns Two
Now in its third year, the Center for Translational Muscle Research (CTMR) continues to accelerate and expand skeletal muscle research, facilitate novel insights into muscle pathologies, and move therapeutics toward the clinic and the marketplace. ISCRM faculty member Mike Regnier, PhD, leads the Muscle Center, which is based on UW Medicine’s South Lake Union campus.
ISCRM Returns to Chehalis
In 2018, more than 40 ISCRM faculty members and students led a STEM camp for students in Lewis County, Washington. This spring, ISCRM returned to W.F. West High School in Chehalis to help a cohort of Molecular Genetics students expand their zebrafish lab.
Nudging Cells to Repair Damaged Retinas
In an approach that could someday be used to help repair the retinas in patients who have lost vision due to macular degeneration, glaucoma and diabetes, researchers led by ISCRM faculty member Tom Reh, PhD have induced non-neuronal cells to become retinal neurons.
Expanding Horizons in Science
Now in its fifth year, the ISCRM Fellows program has propelled the careers of more than 60 young scientists, representing 28 labs and 13 departments. The ISCRM fellows have advanced research on dozens of diseases, innovated new technologies, and contributed to more than 60 published papers.
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.