ISCRM Labs Mount a Rapid, Coordinated Response to COVID-19
Dr. Silvia Marchiano and Tim Martins PhD are just two members of the ISCRM community involved in COVID-19 research efforts underway. JISCRM

All around the world, researchers are mounting an urgent response to the COVID-19 pandemic.  The UW Institute for Stem Cell and Regenerative Medicine (ISCRM) is well-positioned to join this global effort. Over the last decade, ISCRM has built a diverse community of biologists, pathologists, physicians, engineers, and other specialists who are now working together on multiple fronts to combat COVID-19 through automated drug discovery, disease modeling, donations to the frontline, and other efforts. Here are some of the ways ISCRM is joining the fight against COVID-19.

Saving Lives with Automated Drug Screening
High-throughput screening is an automated technology that makes it possible to identify potential drugs with incredible speed. In ISCRM’s Quellos High-Throughput Screening Core researchers have already seen the benefits of automated drug screening for cancer patients. Now, an ISCRM team, working in partnership with Dr. Mike Gale, UW Professor of Immunology, will use that technology to test thousands of drugs that could be effective against COVID-19, saving precious time in the race for treatments. The project, sparked by ISCRM co-founder Dr. Randy Moon, will take place in a highly-secure lab at UW Medical Center, where Tim Martins, PhD, the Quellos Core Director, will treat live SARS CoV-2, the virus that causes COVID-19 with every known approved drug in a quest to find a vulnerability to target that perhaps blocks infection or prevent replication. A hit would be an important lead for investigators to explore as a potential therapy or a stepping stone to clinical trials.

Organoids like this one grown from stem cells enable researchers to study how disease begin and how to stop them.

Using Stem Cells to Study COVID-19’s Impact on the Heart, Lung, Brain and Kidney
ISCRM researchers have pioneered the use of stem cells to conduct “disease-in-a-dish” experiments, a technology that allows scientists to efficiently understand how diseases begin and how to stop them. Now, that approach is being used to answer critical questions about the nature of COVID-19.  Dr. Silvia Marchiano, a Postdoc in the Murry Lab, is leading a collaborative effort to explore exactly how COVID-19 impacts heart functioning by turning stem cells into cardiac muscle cells. What the research team learns could help doctors determine which patients are at increased risk of infection or how they might respond to certain drugs. Key partners in the investigation include ISCRM faculty members Nate Sniadecki PhD (Mechanical Engineering) and Hannele Ruohola-Baker PhD (Biochemistry). The ISCRM team is collaborating with Mike Gale PhD from the Department of Immunology. At the same time ISCRM faculty members Jessica Young PhD and Beno Freedman PhD are preparing to use stem cell-based tools, called organoids, to study how COVID-19 affects the brain and kidney.

 

Astronaut Jessica Meir with an engineered heart tissue chamber aboard the International Space Station. Photo courtesy of NASA

Adapting Space-Based Technology
Earlier this year, Nate Sniadecki and his lab sent engineered heart tissue into space to study how microgravity affects cardiac functioning. For a month, the earth-bound researchers received real-time data from orbit, courtesy of tiny sensors measuring every beat of the engineered hearts. Now that technology is moving from the International Space Station to a secure biosafety lab with advanced containment at the University of Washington Medical Center. As part of the broader ISCRM effort to understand the impact of COVID-19 on the heart, Sniadecki and his team will remotely monitor the health of engineered heart tissue infected with the virus, reducing the amount of time scientists will need to spend in hazardous environments.

ISCRM faculty member Patrick Boyle PhD (Bioengineering) Photo: Joseph K. Yu

Using Artificial Intelligence to Predict Heart Failure Risk
ISCRM faculty member Patrick M Boyle, PhD (Bioengineering) and his partners in the departments of cardiology and epidemiology are devising a plan to use artificial intelligence to help frontline care teams predict risk for heart complications in COVID-19 patients (e.g., inflammation resulting from viral infection of the heart, aberrant heart rhythms, sudden cardiac death), potentially making it easier for doctors and nurses to respond to life-threatening situations while reducing their own exposure to the virus. The researchers have already disseminated an intake protocol to gather clinical data on COVID-19 patients admitted in the UW Health Care System and are working with a network of collaborators to obtain similar insights from hard hit cities and countries around the world. Key collaborators on the research team include Dr. Arun Sridhar, Dr. Neal Chatterjee, Dr. Jeanne Poole (UW Cardiology), and Dr. Alison Fohner (UW Epidemiology).

Caring for Cancer Patients During the COVID-19 Crisis
Cancer patients are at heightened risk for complications caused by COVID-19. Immunosuppression compromises the body’s ability to fight a virus. Blood supply shortages, like the one we are experiencing now, could impact care for those requiring transfusions. And developing a fever with low blood neutrophil count (the number of “fighter” white blood cells) would lead to more emergency room visits and hospital admissions at a time when medical centers are near or over capacity with COVID-19 patients.

Dr. Pamela Becker, Professor of Medicine in the Division of Hematology at UW Medicine, Physician at Seattle Cancer Care Alliance, and ISCRM faculty member

To address these concerns, ISCRM faculty member Dr. Pamela Becker, a world leader in cancer care and research, twice convened a subcommittee of the National Comprehensive Cancer Network Hematopoietic (NCCN) Growth Factors Panel, a group of researchers, physicians, and pharmacists that she chairs. The goal was to develop short term recommendations designed to minimize ER visits and hospitalizations, as well as reduce the need for red blood cell and platelet transfusions to adjust to low blood supply. Based on rapid institutional reviews from the sites, Dr. Becker updated the recommendations, which were posted on the NCCN COVID-19 Resources site on April 2nd.

Among the panelists were Gary Lyman, MD, MPH of the Fred Hutchinson Cancer Research Center and Laura Alwan, PharmD, BCOP, a pharmacist with the University of Washington and Seattle Cancer Care Alliance, as well as representatives from 16 other NCCN sites from all over the United States.

ISCRM labs have sent boxes of urgently needed personal protective equipment to UW Medical Center.

Sending PPE to the Frontlines
Frontline care teams around the world are facing severe shortages of personal protective equipment. ISCRM labs have responded to this crisis by donating their own supplies and repurposing cutting-edge technology typically used for research. The Murry, Chamberlain, Bomsztyk, Sniadecki, and Kwon Labs, and the Quellos High Throughput Screening Core, have sent boxes of urgently needed masks and gloves to UW Medical Center. And the Stevens Lab is taking part in a broader UW Medicine effort, coordinated by Dr. Robert Sweet, to 3D print face shields and other PPE using tools normally used to print 3D models of human tissue and organs for disease modeling.

Fighting the Cytokine Storm
Hannele Ruohola-Baker PhD, a Professor of Biochemistry and Associate Director of ISCRM, uses stem cells to study the basic mechanisms of life. Specifically, her team is focused on the pathways that drive human development and the molecular and cellular processes that give rise to diseases. Over several years, the researchers in the Ruohola-Baker Lab have found that multiple computer-designed proteins, developed in partnership with the Institute for Protein Design, are potential countermeasures against sepsis – an inflammation triggered by the body’s immune response to infections. Now Ruohola-Baker and her ISCRM colleagues Beno Freedman PhD, Julie Mathieu PhD, and Hongxia Fu PhD are preparing to use stem cells from the Allen Institute for Cell Science and organoids from the Freedman Lab to test whether those computer-designed proteins could be a treatment for the cytokine storm that damages the heart, kidney, blood vessels and other tissues in severe cases of COVID-19.

Incubating Innovation
Innovation at ISCRM has produced successful companies that are now generating medical breakthroughs and contributing to the economic vitality of our state. Nimble, specialized Biotech firms like NanoSurface Biomedical, Inc. are crucial allies in the effort to solve the COVID-19 crisis and help bridge the lab to the clinic. Scientists at NanoSurface are generating stem cells that will be used to study how COVID-19 impacts heart functioning. Sustaining that spirit of innovation is imperative if we are going to stay ready for future epidemics and health challenges.