For ISCRM, the year 2020 has been marked by adversity, ingenuity, collaboration, reflection, and growth. The global response to COVID-19 has shown us that working together in the pursuit of a higher purpose can yield progress with unimaginable speed. At the same time, acts of racial injustice have reminded us that we must do much more within our own community to create a truly diverse, equitable, and inclusive research environment. We are proud to share the following report with all of our supporters who have helped make these accomplishments possible.
Chuck Murry, Director | Hannele Ruohola-Baker, Associate Director | Jen Davis, Associate Director | Nate Sniadecki, Associate Director
Over the last twelve years, philanthropic support has helped ISCRM unite biologists, physicians, and engineers confronting diseases that have tormented humanity for centuries. Here are a few ways the dynamic research community you helped build is now using its combined strength to help frontline medical providers address the urgent and long-term threats posed by COVID-19.
Brain, Heart, and Kidney
This summer, the Murry, Sniadecki, and Gale Labs used stem cell and tissue engineering technologies to show, in unprecedented detail, why so many COVID-19 patients are dying from heart failure. The findings could have major implications for patient care. Other ISCRM teams are using stem cells and organoids to study how COVID-19 impacts the lung, brain, and kidney.
Partnering for Progress
With a $3.4 million grant from the Department of Defense, the Ruohola-Baker Lab is partnering with the Institute for Protein Design (IPD) to explore whether a combination of computer designed proteins could help treat life-threatening sepsis caused by COVID-19 and bind to the signature spikes of the virus, preventing it from entering and infecting cells in the first place.
Accelerating Drug Discovery with High Throughput Screening
In ISCRM’s high-throughput screening facility, we have seen the benefits of automated drug screening for cancer patients. An ISCRM team is now using that technology to rapidly test thousands of combinations of drugs that could be effective against COVID-19, saving precious time in the race for treatments.
Research shows that diverse teams working together and capitalizing on innovative ideas and distinct perspectives outperform homogenous teams. Scientists and trainees from diverse backgrounds and life experiences bring different perspectives, creativity, and individual enterprise to address complex scientific problems.
– NIH, November 2019
Confronting racism wherever it exists is not only a matter of human dignity and human rights. It is also critical for science. To reach our full potential as an institute, we know our research community must represent and serve all members of society, including those from historically marginalized populations. That’s why ISCRM is dedicating more resources to recruiting and supporting faculty and students from underrepresented groups and taking the time to collectively learn to recognize and disrupt racism in our institute, university, and community. We look forward to updating you on our progress in 2021 and sharing how you can support these efforts.
In 2019, the Heart Regeneration Program, incubated in ISCRM, moved to Sana Biotechnology, where it is currently moving toward human clinical trials that could begin as soon as 2023. In the meantime, heart research at ISCRM continues to produce discoveries that are opening the door to potential new treatments for heart disease.
COVID-19 and the Heart
Using remote technology originally designed for the International Space Station, the Murry and Sniadecki Labs partnered with the Gale Lab in the Department of Immunology to demonstrate that COVID-19 is capable of infecting cardiac organoids directly. The findings could help doctors determine which patients are at increased risk of infection or how they might respond to certain drugs.
Colorful Way to Study Heart Formation
Danny El-Nachef, PhD, a former postdoc in the Davis and Sniadecki Labs, published research that further validates rainbow reporter technology – a tool that allows researchers to track how stem cells behave during the earliest stages of human heart development. El-Nachef’s work has drawn international interest from labs hoping to better understand how the heart forms and how it can be regenerated after injury.
Predicting Risk of Heart Disease
A major grant from the American Heart Association is funding a collaboration that brings together world-class expertise in cell engineering, data science, and predictive modeling. ISCRM faculty members Jen Davis PhD, and Farid Moussavi-Harami, MD are partnering with Tom Daniel, PhD in the Department of Biology to develop tools that physicians can use to quickly and accurately identify risk of heart disease using a patient’s genetic make-up.
In a nutshell, tissue engineering is what happens when biologists who ask why meet engineers who ask what if. At ISCRM, that means using natural and synthetic materials to recreate the structure and function of cells, organs, vessels, and other tissues. In 2020, ISCRM researchers published dozens of papers detailing efforts to solve real problems using feats of tissue engineering that are breaking boundaries in medicine. Here are just a few examples:
“Ultimately the goal is to improve other disease modeling technologies that are critical for drug testing and to bring us closer to artificial tissues for therapy. Here we demonstrated the viability of a tool that uses genetic engineering, 3D printing, and biomaterials all working together in a system.”
Kelly Stevens, PhD
Controlling Cells with Heat
In another tissue engineering breakthrough, a research team led by Kelly Stevens, PhD demonstrated that heat can be used to turn on selected genes in three-dimensional tissue models. In their investigation, Stevens and former graduate student Daniel Corbett, PhD printed 3D channels similar to the vessels that carry blood through the liver. Next, they injected hot water into the channels and engineered liver cells to express a protein that makes fireflies light up – creating a beacon that helped them track how the cells responded.
Studying Human Biology in 4D
Cole DeForest, PhD received a prestigious five-year, $1.9 million grant from the NIH to mimic, exploit, and quantify biological systems in full 4D complexity. DeForest and his collaborators are using sophisticated biomaterials to study how human biology changes as cells move through space and time. The ultimate goal is to provide researchers with new tools to study how the body works, and to understand what goes wrong when it doesn’t.
Breaking the Capillary Barrier
Capillaries are the most abundant vessels in the vast vascular network that supports our tissue and organs. These microvessels, which enable the exchange of nutrients and waste and carry blood from the arteries to the veins, are challenging to study and difficult to recreate in the lab. Earlier this year, ISCRM faculty member Ying Zheng, PhD led the first research team to successfully engineer capillaries using exquisitely precise laser technology, opening the door to more detailed study of malaria and all small vessel diseases.
In the nucleus of nearly every human cell, approximately three billion base pairs of nucleotides, spread across 23 pairs of chromosomes, are twisted into double strands of replicable genetic material. This is DNA. Each DNA sequence that contains instructions to make a protein is known as a gene, while a genome is the entire set of an organism’s genetic material. Genomics, in turn, is the detailed study of how all those genes work together to code for all human function.
To supercharge the study of genes and disease, ISCRM is creating a Genomics Core. This facility within the institute will be set up to perform complex screens more rapidly and accurately than any single scientist could do alone, accelerating research projects, strengthening federal grant applications, and helping to retain and recruit the greatest minds in biology and engineering.
This technology has widespread implications for human health. The more we know about the genes involved in a disease, how they network together, and how the mutations that cause a disease occur, the better we can diagnose and treat patients battling cancer, Alzheimer’s, diabetes, heart disease, and other conditions impacting billions of people around the world.
Funding a Genomics Core means fast-tracking discoveries that are reshaping medicine. Your support would help provide the staff and equipment ISCRM labs need to translate genetic insights into powerful new diagnostic tools and treatments that confront the root causes of disease.
Testing Potential Treatment for Kidney Disease
Beno Freedman, PhD and his collaborators received a $4 million grant to test a new therapeutic approach for kidney disease. The treatment would use fragments of antibodies known as nanobodies to help stimulate regeneration of highly specialized, hard-to-grow cells.
Developing New Treatments for Type 1 Diabetes
Laura Crisa, MD, PhD, Vincenzo Cirulli, MD, PhD, and Cole DeForest, PhD, received a multi-Investigator NIH Grant from the NIH to develop innovative strategies for the transplantation of stem cell-derived pancreatic islet cells.
Watch a video of Cirulli and Crisa discussing their diabetes research here.
Investigating a Gene Implicated in Alzheimer’s Disease
Jessica Young, PhD and Sumie Jayadev, MD used stem cells to produce new evidence that a gene known as SORL1 contributes to some types of Alzheimer’s disease. The findings also help explain why so many promising treatments have been unsuccessful in clinical trials.
Studying the Genetics of Osteoporosis
Fueled by a major grant from the NIH, Ron Kwon, PhD and his lab are on a mission to confront the root cause of osteoporosis. The investigators are using cutting-edge imaging technology to identify genetic risk factors for the disease and to identify new therapeutic targets.