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Brown researchers combat COVID-19 in the lab, clinic

University laboratories pause cancer, fluid mechanics research, turn their knowledge, resources to COVID-19

While researchers across the University had to close their doors and hang up their lab coats for the foreseeable future on March 18, some labs have found ways to keep their doors open for the benefit of the community amid the COVID-19 crisis. Donning personal protective equipment, researchers are reapplying their relevant expertise from other fields and working urgently to seek solutions to the novel coronavirus’ transmission and infection. 

Included in the effort to pursue COVID-19 related projects are labs situated in the Department of Pathology and Laboratory Medicine belonging to Associate Professor of Pathology and Laboratory Medicine and Associate Director of Coagulation and Transfusion Medicine at Lifespan Jeffrey Bailey and Associate Dean for Oncologic Sciences at the Alpert Medical School Wafik El-Deiry, who also directs Brown’s Cancer Center. At the School of Engineering, Assistant Professor of Engineering Daniel Harris is collaborating with Professor of Engineering Roberto Zenit on a project aimed at curbing the ventilator shortage. 

As the United States now has more confirmed COVID-19 cases than any other country, these researchers are working to provide some answers to the many scientific questions posed by COVID-19 and the unprecedented impact it has had on global society. 

Jeff Bailey and the University’s COVID-19 Research Task Force

Operational for just over a week, the University now has a COVID-19 research task force chaired by Bailey.  

The task force was “started by the Dean of the Medical School, but it's operating more broadly to try to bring people together,” Bailey said. Its goals are to optimize communication between researchers at Brown working on the virus and to help push current research projects forward. 

Bailey was involved in a response to the Ebola outbreak of 2014 when he was an assistant professor at the University of Massachusetts. “The U.S. is not used to outbreaks. … It really requires rapid thinking, rapid response and rapid organization,” he said, adding that lessons learned in Africa at the peak of the Ebola crisis could guide scientists and public health officials now. 

Bailey is currently working on a project tied to Rhode Island Hospital involving the treatment of COVID-19 with convalescent plasma, a method that involves transferring the component of the blood containing COVID-19 antibodies from a recovered patient to a new one. “The FDA just cleared it for what we call compassionate use,” Bailey said, meaning it can be given to patients on a case-by-case basis. 

According to Bailey, Lifespan is also involved in a multicenter trial that is testing another potential treatment, a drug named Remdesivir. It was developed for Ebola, “but it seems to have potential broad effects, at least in the lab,” in the context of COVID-19, he said.

Wafik El-Deiry and a BEACON of hope: A link between cancer and coronavirus

El-Deiry, a medical oncologist who had not previously studied coronaviruses, respiratory diseases or pandemics in depth, was inspired to reorient his research to focus on COVID-19, in part because many of its biological mechanisms are reminiscent of the disease he has devoted his life’s work to: cancer. 

Realizing he had the knowledge and laboratory resources to make sense of the virus’s mode of infection, El Deiry, alongside other scientists from his research group, are volunteering their time to study COVID-19 as members of the Brown Experimentalists Against COVID-19 group, aptly referred to as BEACON. 

“There (are) some parallels between some of the symptoms and phenomena that patients are experiencing and things we in the world of cancer and cancer research are very familiar with. We use some of the same drugs, we use other drugs to treat side effects, so there is a fund of knowledge that already exists,” he said. 

El-Deiry only arrived at the University in January 2019, but his research team has focused on better understanding tumor suppressor genes and seeking cures for cancer for over two decades, during which they made pivotal discoveries at the basis of cancer biology and treatment.

When the University started making arrangements to temporarily shutter research labs, “we basically stopped doing new experiments, we started freezing our cancer cells that we grow in culture,” El-Deiry said.

After spending time in the clinic with his patients, El-Deiry saw that as research had started to scale back, healthcare workers were facing increasingly intense workloads while national PPE shortages threatened their safety. 

“What about the researchers?” he asked. “What can we do at a time like this? Should we just sit back and do nothing and wait?” He started to consider how his research group could use the methods and knowledge they’d acquired to help combat the crisis, asking himself, "How could we mobilize? How could we do things in a safe manner? How could we make important contributions that may matter now?” 

For El-Deiry and his team, studying COVID-19 was the answer. Without using the actual COVID-19 virus in the lab, the researchers are looking into multiple stages of the COVID-19 infection — from the protein that facilitates its movement into a cell, to the inflammatory response that is triggered in the lungs upon infection.   

Spike protein,” a small projection on the surface of the COVID-19 virus, is the microscopic culprit responsible for the virus’s ability to latch onto a human cell. The El-Deiry lab is in line to receive isolated spike protein samples for testing. When a person becomes infected with COVID-19, the virus may travel through the throat to their lungs, where these proteins help the virus bind to ACE2, a receptor in the membrane of human host cells, infiltrating the cell, El-Deiry said. 

There are links between the prevalence of these ACE2 receptors and the populations who may be most susceptible to infection, El-Deiry noted. People being treated for high blood pressure are among those shown to have higher ACE2 levels, he said, adding that “The elderly are particularly sensitive to (COVID-19), and patients with comorbidities, including, notably, patients with cancer, are at high risk.” 

El-Deiry and fellow scientists now hope to help those infected by COVID-19 by finding a means of inhibiting the ACE2 receptor or of enhancing the body’s immune response to combat the potentially deadly invaders. The immune system fights COVID-19 similarly to how it responds to cancerous cells. Complications can develop, however, when the protein IL6 triggers a “cytokine storm,” which is an excessive release of cytokine proteins that cause inflammation.

One antidote to the virus may lie in already existing pharmaceutical drugs. Chloroquine and hydroxychloroquine are examples of drugs that some have proposed as potential treatments for COVID-19, though much of the science behind how they could work remains unknown, El-Deiry said, adding that they have been used in cancer clinical trials. 

Tocilizumab is another drug, “approved very recently to ... treat COVID-19 pneumonia,” that is known to impede IL-6 and cytokine storms. “We can certainly look at how these drugs affect the activity of this innate immune system that we (have studied) in the lab every day for more than two decades,” El-Deiry added.

The researchers in El-Deiry’s lab also plan to analyze the role of killer T-cells — another one of the body’s natural defenders. They have designed methods to test these cells, which he hopes will enable them to analyze how various drugs impact the immune system’s response to the novel coronavirus. Even though these experiments were originally designed with cancer in mind, “we could pivot instantly,” El-Deiry said. 

Though the timeline of their work remains uncertain, El-Deiry said that “one of our strengths is in this area of translational research, ... the idea of taking discoveries and knowledge from the lab and moving into the clinic as quickly as possible.”

The researchers would also “love to collaborate if (they) make meaningful progress in the coming weeks,” El-Deiry said.

Delighted to collaborate with @tcellsrus @MDAndersonNews through the work of #BEACON (Brown Experimentalists Against COVID-Nineteen) @BrownMedicine @BrownUniversity @BrownUResearch hoping to learn, contribute new knowledge, and make a difference #eldeirylab

In the current climate, El-Deiry said, “basic science is important, and research is important. And it can save lives, and it can bring hope.”

Daniel Harris, Roberto Zenit and BRUNO2: Engineering a Solution to the Ventilator Shortage

Harris and Zenit are leading an effort at the University entitled “BRUNO2” to design a ventilator — a lifesaving device that delivers air to the lungs — that could help mitigate the COVID-19 ventilator shortage. The project involves incorporating 3-D printed materials and open-source electronics to design a ventilator that could be practically and cheaply made in areas where ventilators are in high demand. 

An invitation to participate in the “Code Life Challenge” with the same goal sparked the project, and the researchers’ abilities were well suited to undertaking the task. They have traditionally focused on creating fluid devices, Harris wrote in an email to The Herald. 

Researchers put out calls for collaborators on social media and announced the name of the project, BRUNO2, Sunday. The BRUNO2 group currently consists of fifteen Brown Engineering affiliated members, two practicing engineers, three medical doctors and three medical students, according to Harris. 

Elizabeth Austin ’20, an engineering student, helped design the BRUNO2 logo that was shared across social media platforms. 

But “this challenge is only the beginning of our efforts,” Harris wrote, adding, “We have just submitted documentation for our first prototype but have a lot of work to do in the coming weeks to add functionality and fully test the design.”

Tuesday, the Harris Lab tweeted a video of the prototype ventilator as it pushed air in and out of a red balloon — expanding and compressing the balloon as the ventilator would a person’s lungs. The tweet had a short but hopeful caption: “It’s … breathtaking!” 

On Wednesday, they released another video. 

Beyond proud of what the #bruno2 team has been able to accomplish in just over a week for our first major deadline. Honored to work aside such motivated and talented individuals. @brownengin @BrownUniversity

A unified effort with government, healthcare professionals across Rhode Island  

In addition to these labs, other “Brown researchers have been working closely and continually on several fronts with state government officials and health care professionals to help expand the capacity to test and treat patients,” Vice President for Research Jill Pipher wrote in a statement to The Herald. 

“We do have an obligation to address the important issue at this time, so it’s great to be within an environment that makes that possible,” El-Deiry said. “We still want to be very careful with everything we do, but … maybe we could make a difference that impacts on the rest of the world from right here where things maybe aren’t as bad at this time.”


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