We are pleased to present this brief report on a year of innovation, collaboration, and discovery from the Institute for Stem Cell and Regenerative Medicine (ISCRM). As our scientific community continues to expand, so does the breadth of our research. In the pages that follow, you’ll see achievements in heart regeneration, Alzheimer’s disease, and tissue engineering alongside exciting advances in malaria, autism, and dentistry made possible in part by support from generous donors like you.
Chuck Murry, Director | Hannele Ruohola-Baker, Associate Director | Jen Davis, Associate Director | Nate Sniadecki, Associate Director
Progress Against Disease
Gene Edits Suppress Irregular Heartbeats
ISCRM Director Chuck Murry and his team have tackled a major obstacle in the ongoing heart regeneration effort. In a study published in April, the researchers show that a gene-editing approach developed in the Murry Lab safely reduces irregular heartbeats (known as arrhythmias) caused by engrafted stem cells that were usurping pace-making duties, preventing the host heart from setting its own rhythm. Work is now underway to demonstrate that the gene-edited cells are not only safe, but also capable of remuscularizing the walls of infarcted hearts–and, ultimately, improving wellbeing for heart disease patients everywhere. Critical support and expertise was provided by the Garvey family, the WashingtonResearch Foundation, and Sana Biotechnology.
Did You Know? Philanthropy supports preliminary research that leads to millions of dollars in federal grants.
A Surprising Finding About the Cause of Polycystic Kidney Disease
ISCRM faculty member Beno Freedman, PhD, studies polycystic kidney disease (PKD), an incurable inherited disorder that affects more than 600,000 people in the United States. The disease causes fluid-filled cysts which can affect kidney functioning and lead to kidney failure, an outcome requiring dialysis or transplant.
To better understand how the disease takes hold at the molecular level, the Freedman Lab invented a new tool called a human kidney organoid on a chip. This device, which allows a fluidic combination of water, sugar, amino acids, and other nutrients to flow over the organoids (gene-edited to mimic PKD), played a key role in a January 2023 study, which revealed that cysts appear to grow by pulling in sugar-rich fluid, not by secreting the liquid, as had been expected. The discovery suggests that drugs approved to block sugar uptake in the kidneys could have therapeutic potential for PKD.
“We know clumping of tau causes a lot of the neurodegeneration seen in Alzheimer’s. We wanted to better understand how the various functions of tau are altered or lost and how those disruptions contribute to disease beyond the abnormal protein aggregation.” – Tiara Schwarze-Taufiq, PhD
NIH Grant Advances Alzheimer’s Research – And Launches a Career
Tiara Schwarze-Taufiq joined the lab of ISCRM faculty member Jessica Young, PhD as an undergraduate researcher. In the summer of 2021, she received a state-funded ISCRM fellowship that allowed her to probe a pivotal question about a protein, known as tau, implicated in the onset of Alzheimer’s disease. Now, the preliminary data from her experiments has helped lead to an NIH grant that will support a deeper dive into the consequences of tau mutations. Adding a grace note, funding from the grant allowed Young to hire Schwarze-Taufiq as a full-time research scientist.
In other recent research from the Young Lab, a study led by Acting Instructor Swati Mishra demonstrated that disruptions in the endo-lysosomal network caused by mutations to the SORL1 gene, which is linked to Alzheimer’s disease risk, can be rescued by molecular chaperones. This discovery points to a potential new therapeutic pathway for Alzheimer’s disease.
Did You Know? Philanthropy has the power to launch the careers of young scientists.
Engineering Advances
Light Activated Proteins
An April 2023 study from the Cole DeForest Research Group described the use of light to activate protein functions both inside and outside of living cells. The new method, called light-activated SpyLigation, can turn on proteins with the flick of a light switch, enabling spatiotemporal control of cell fate and genome editing. This technology has potential multiple uses in tissue engineering and regenerative medicine.
Regrowing Enamel
In a breakthrough that could lead to transformative possibilities in dental care, scientists in the Ruohola-Baker Lab, the UW School of Dentistry, and theInstitute for Protein Design(IPD) created stem cell-based organoids that secrete the proteins that form enamel, the outer coating of our teeth, and the hardest substance in the human body.
Modeling Cerebral Malaria in 3D
The Zheng Lab, in partnership with Dr. Joe Smith at Seattle Children’s Research Institute, unveiled a modeling tool for probing cerebral (brain) malaria inflammation in 3D engineered human brain microvessels. Findings published in a November 2023 paper revealed new information about the risk to blood vessels in the brain that results from interplay of the mosquito-borne malaria parasite and a protein involved in the body’s immune response to infection.
“By putting fibroblasts into these materials, we can study the conditions which produce scar, and perhaps whether reversing those conditions could calm the cells back down. These material systems have the potential to unlock our understanding of scarring in the heart, enabling us to develop the next generation of treatments for this deadly disease process.” – Jen Davis, PhD
Extracting Cells From Hydrogels
ISCRM Associate Director Jennifer Davis, PhD and her lab are on a mission to harness the cellular mechanisms of scarring to improve outcomes for millions of heart disease and heart attack patients. But, to control scarring, the researchers need to understand what makes fibrotic cardiac cells tick – and, to do that, they need a way to observe, manipulate, and evaluate the cells in their natural state. Encasing cells in hydrogels is one way to do that, with a catch. Removing cells without disturbing them has proven to be difficult. However, a collaboration with the Cole DeForest Research Group, has demonstrated a new method for cell extraction using engineered versions of an enzyme called sortase that have evolved to recognize and break specific peptide sequences.
Did You Know? Philanthropy allows multidisciplinary partnerships to become innovation multipliers.
Capping a Career: Professor Carol Ware
Finding a Sweet Spot for Embryonic Stem Cell Cultivation
Professor Emeritus Carol Ware, PhD, a founding member of ISCRM and the inaugural director of the Ellison Stem Cell Core, has helped many ISCRM labs answer questions about early human development by using different types of stem cells to model a wide range of diseases and biological processes.
In 2014, Ware generated the first human embryonic stem cell in a naïve state, which more closely resembles a pre-implantation stage of development. (Cells that are derived from a post-implantation stage are known as primed.) Successfully generating and stabilizing naïve cells opened up new possibilities in embryonic modeling.
One challenge has been how to produce self-sustaining cell lines from embryos frozen at the blastocyst stage. This year, in a paper published in Stem Cell Review and Reports, Ware and ISCRM faculty member Julie Mathieu, PhD revealed that later naïve cells have a very stable, but reversible, imprint pattern that allows for much more thorough differentiation into various cell types and that a molecule know to inhibit a checkpoint (CHK1) associated with cancer treatment helps with the derivation of naïve cells.
Growing Our Research Community
In 2023, ISCRM welcomed six new faculty members who joined the university through joint recruiting efforts with different departments.
Nobuhiko (Nobu) Hamazaki, PhD, OBGYN and Genome Sciences
The Hamazaki Lab will explore gene expression in the earliest stages of development, with a long-term hope of pursuing new treatments for infertility and other health challenges.
Yusha Katie Liu, MD, PhD, Division of Plastic Surgery
The Liu lab will study peripheral nerve injuries and will work to translate mechanistic findings into therapeutic applications to improve functional outcomes in patients.
Joe Powers, PhD, Lab Medicine & Pathology and Mechanical Engineering
The Powers Lab studies the cellular and molecular mechanisms underlying various forms of heart diseases, with a focus on multi-scale biomechanics, mechanobiology, and biological structure.
Feini (Sylvia) Qu, PhD, Orthopaedics and Sports Medicine and Mechanical Engineering
The Qu Lab will explore the cellular and molecular pathways of composite musculoskeletal tissue regeneration, especially the bones and connective tissues that link our limbs and joints.
Jenny Robinson, PhD, Orthopaedics and Sports Medicine and Mechanical Engineering
With a focus on promoting regeneration, the Robinson Lab uses polymer-based biomaterials to explore how cells respond to changing chemical and mechanical properties in their tissue microenvironments.
Min (Mia) Yang, PhD, OBGYN
Dr. Yang and her lab will utilize advanced 3D stem cell models and animal models to gain fresh insights into early embryonic processes, with the goal of improving reproductive and maternal-fetal health.
Quick-Hit Highlights from 2023
FDA Approval for Gene Therapy
On June 22, 2023, the FDA approved the first-ever gene therapy for Duchenne Muscular Dystrophy – an approach to treating the disease, developed by Sarepta Therapeutics, that is based in part on technology designed by ISCRM faculty member Jeff Chamberlain, PhD and his collaborators at UW Medicine. In related news, the NIH renewed the Sen. Paul D. Wellstone Muscular Dystrophy Specialized Research Center, directed by Dr. Chamberlain, for another five years.
Progress Against Parasitic Worms
Research published this year by Jakob von Moltke, PhD describes how our body generates an enigmatic cell type, known as tuft cells, that detects parasitic worms and helps to mobilize an immune response. Worm infections, which are prevalent around the world, can be especially harmful for children who lack access to adequate sanitation.
Studying a Gene Linked to Autism
ISCRM faculty member Smita Yadav, PhD and her lab used rodent and stem cell models to shed new light on the mechanisms by which a gene strongly linked to autism and other neurodevelopmental conditions triggers pathological changes to the neuronal membrane that contribute to intellectual disabilities. The researchers believe these findings point to a promising target for potential therapies.
ISCRM Undergraduate Summer Program
The ISCRM Undergraduate Summer Program, now in its second year, provided a combined cohort of ISCRM Fellows, Bothell Fellows, and ISCRM REU students with paid summer jobs in labs, weekly training in professional skills related to publishing, presenting, and communications, and an opportunity to connect with other undergraduate researchers from around the world.
STEM Outreach and Community Engagement
ISCRM Visits Students in the Yakima Valley
In February and March, researchers representing seven ISCRM labs journeyed to Toppenish High School in the Yakima Valley to lead an interactive lesson focused on the pancreas and diabetes and another on stem cells and organoid technology. In June, the Toppenish students travelled to Seattle for a tour of ISCRM’s South Lake Union campus, where they examined high-resolution photos of stained organoids in the Garvey Imaging Core, peered at beating heart cells in the Ellison Stem Cell Core, and learned about 3D bioprinting technology in the Stevens Lab.
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 Elizabeth Damore, director for philanthropy, at edamore@uw.edu.