“Given the time pressure to find treatments and ultimately prevent COVID-19 and the terrible loss of life and economic disruption that are damaging the well-being of individuals, families, and entire countries,” says Carol Ludwig, MD, president of the foundation, “we felt it was important to lend early support to this group of talented Yale scientists who are working tirelessly to find approaches with the potential to benefit large numbers of people.”
The gift includes funding for research led by Akiko Iwasaki, PhD, Waldemar Von Zedtwitz Professor of Immunobiology, in collaboration with Aaron M. Ring, MD, PhD, assistant professor of immunobiology, and Craig Wilen, MD, PhD, assistant professor of laboratory medicine and of immunobiology. Their combined laboratories will analyze components of the blood and immune systems of COVID-positive patients via flow cytometry and other methods. The more precisely they are able to sort out the many components of the immune response to SARS-Co-V2, the more likely they will be to develop targeted treatment strategies, use biomarkers to predict the success of each treatment option, and determine which immune system components will help protect the patient from disease and which may exacerbate it.
Wilen’s lab is also working to identify drugs and novel targets, using a combination approach. One part involves screening 680 FDA-approved drugs for anti-viral activity, and then testing their efficacy with tests involving infectious virus. The second is analyzing the human genome to identify genes that may open the door to SARS-CoV2 infection, with the hope that those genes can become targets for new therapies. The third is to learn how the virus causes disease by using single-cell RNA sequencing to sort out the genes expressed by specific cells in the presence versus the absence of the virus.
The labs of Ring and of Andrew Wang, MD, PhD, assistant professor of internal medicine and of immunobiology, are collaborating on answering the important question of whether a patient’s cells are destroyed directly by the SARS-Co-V2 virus or by powerful elements of the infected person’s immune system that the virus triggers. That work, supported by the gift, will include defining the roles of several cell death pathways in the progression of COVID-19 disease, and the potential of making them therapeutic targets.
David A. Hafler, MD, chair and William S. and Lois Styles Professor of Neurology, and professor of immunobiology, will use some of the funding to work to develop immunotherapies to treat COVID-19, with a particular focus on the co-inhibitory receptor TIGIT. Hafler and colleagues have identified TIGIT as playing a central role in orchestrating T cell activation in autoimmunity, cancer, and viral expression. One of their goals is to use multi-omics single cell analysis to explore T cell immune profiles in patients with mild and severe manifestations of COVID-19 compared with healthy individuals. They hope this work will also have applications to pandemic viruses that might arise in the future.
The gift is also supporting work led by Richard Bucala, MD, PhD, Waldemar Von Zedtwitz Professor of Medicine (Rheumatology) and professor of pathology and of epidemiology (microbial diseases). Bucala’s laboratory hopes to develop a vaccine based on an RNA replicon platform that can block transmission of SARS-CoV-2 and also limit future viral outbreaks. Bucala is particularly optimistic about this approach because it has shown promise when applied to other forms of viral infection, can be administered effectively in small doses, and can be produced rapidly in large quantities to enable mass vaccine distribution.
We felt it was important to lend early support to this group of talented Yale scientists who are working tirelessly to find approaches with the potential to benefit large numbers of people.
Carol Ludwig, MD
In addition to providing funding to these specific projects, the Ludwig Family Foundation has provided a generous gift to the COVID Research Resource Fund. This fund may be used at the discretion of Nancy J. Brown, MD, Jean and David W. Wallace Dean of Medicine and C.N.H. Long Professor of Internal Medicine, in her role leading the coordination of research activities related to COVID through CoReCT, the campuswide COVID-19 Response Coordination Team.