Yale Stem Cell Center Faculty Are Studying COVID-19

The COVID-19 pandemic has mobilized investigators at Yale to pivot from their ongoing work to develop vaccines to prevent the disease, assays to detect the disease, and drugs to treat the disease. We are proud to list just a few of the remarkable scientific projects being pursued by members of the Yale Stem Cell Center in fighting against the pandemic.

From the laboratory of Sidi Chen

Chen laboratory is conducting COVID-19 research in the following areas: (1) development of novel therapeutic candidates such as neutralizing antibodies; (2) big data and omics scale analyses using artificial intelligence and machine learning to identify genetic links to disease vulnerability factors; (3) understanding of viral immunology; (4) pilot development of novel coronavirus vaccine candidates.

From the laboratory of Yung-Chi Cheng

We are exploring the potential of herbal medicine for treating COVID 19 patients by studying the formula China recommended and also developing new formula covering all aspects of disease pathogenesis. The current reductionist approach by others for treating patients is too narrow in scope and won't work well by itself. Combination will still be needed. This is what my lab is doing in this area.

From the laboratories of Rong Fan, Stephanie Halene, Diane Krause, Hyung Chun, and Mina Xu

Patients with hematologic malignancies have a higher risk of SARS-CoV-2 infection, determined by their underlying diseases and their treatments. The teams around Drs. Rong Fan, Stephanie Halene, Diane Krause, Hyung Chun and Mina Xu will develop and validate two novel immuno-serological assays that will be deployed to conduct longitudinal measurement of plasma markers and peripheral blood immune cells from COVID19 patients with different hematologic malignancies. They will use their plasma protein assay and single cell microchip to measure a cohort of COVID19 patients with or without hematological malignancies and healthy donors in order to identify potential molecular correlates with immune-mediated pathology and COVID19 disease severity uniquely in hematological cancer patients. These studies will extend to monitoring vaccine-induced humoral, cellular, and immunological responses in patients with hematologic malignancies to understand gaps in immune response to vaccination and how to improve upon it. The grant title: IMMUNO-SEROLOGICAL ASSAYS FOR MONITORING COVID19 IN PATIENTS WITH HEMATOLOGIC MALIGNANCIES, 1U01CA260507-01

From the laboratory of Kevan Herold

We are looking at differences in immune responses in children vs. adults with COVID-19. Our paper was published in Science Translational Medicine: Immune responses to SARS-CoV-2 infection in hospitalized pediatric and adult patients. Carl A. Pierce, Paula Preston-Hurlburt, Yile Dai, Clare Burn Aschner, Natalia Cheshenko, Benjamin Galen, Scott J. Garforth, Natalia G. Herrera, Rohit K. Jangra, Nicholas C. Morano, Erika Orner, Sharlene Sy, Kartik Chandran, James Dziura, Steven C. Almo, Aaron Ring, Marla J. Keller, Kevan C. Herold, Betsy C. Herold. Sci. Transl. Med. 10.1126/scitranslmed.abd5487 (2020).

From the laboratory of Diane Krause

The Krause laboratory is collaborating with Dr. John Hwa and additional faculty members (Alfred Lee, Hyung Chun, Stephanie Halene, Jonathan Siner and others) on the causes of severe morbidity and mortality in COVID19. The cause of death in severely ill patients is usually respiratory failure from acute respiratory distress syndrome and/or disseminated thrombosis (blood clotting). Blood clotting requires activation of circulating factors as well as platelets. In our ongoing work, we have demonstrated platelet hyperactivation in patients hospitalized with COVID19. In a small clinical trial, this Yale team has demonstrated that pharmacological inhibition of platelet aggregation may improve survival in patients hospitalized with COVID19.

From the Laboratory of Haifan Lin

To discover a medicine for treating COVID-19 patients, Dr. Haifan Lin is co-leading two clinical trials with Dr. Miriam M. Treggiari, M.D., Ph.D., Professor and Vice Chair of the Department of Anesthesiology at Yale School of Medicine, to treat moderate and severe COVID-19 patients with a new candidate drug that blocks the assembly and proliferation of the coronavirus. This effort, in partnership with Sound Pharmaceuticals, Inc. (Seattle, WA), was approved by FDA on September 2, 2020 for Phase II clinical trials. The team is moving rapidly to initiate the trials in the Yale-New Haven Health System within the next few months.

From the laboratory of Jun Lu

The COVID-19 pandemic has exposed global inadequacies in therapeutic options against both SARS-CoV-2 and other newly emerged respiratory viruses. The Lu Laboratory has been investigating the feasibility of designing virus-specific anti-viral therapeutics multiple years prior to the emergence of respiratory viral outbreaks. These designed RNA-based therapeutics are being tested to combat both the COVID-19-causing SARS-CoV-2 virus as well as potential future respiratory coronaviruses.

From the laboratory of Richard Sutton

We are exploring various functional assays involving the humoral response against SARS-CoV-2, in both man and preclinical models. A paper that describes a novel cell fusion assay is getting ready for publication; we also have a cell-cell transmission assay that quantifies the ability of Spike to interact with hACE2, and we are developing a cell-free assay that would take only 30 minutes to also quantify this interaction.

From the laboratory of Jean-Leon Thomas

We analyze the anatomical routes of brain invasion by SARS-CoV-2, using COVID-19 mouse models and the technique of i-DISCO+-labelling of whole head preparations combined with light sheet fluorescent microscope imaging. We are also investigating whether and how SARS-CoV-2 infection interferes with a pre-existing proteinopathy in a mouse model of Tauopathy.

We have contributed to the following study of the Iwasaki laboratory, by providing human brain tissue sections from COVID-19 deceased patients’ autopsies: Neuroinvasion of SARS-CoV-2 in human and mouse brain. Song E, Zhang C, Israelow B, Lu-Culligan A, Prado AV, Skriabine S, Lu P, Weizman OE, Liu F, Dai Y, Szigeti-Buck K, Yasumoto Y, Wang G, Castaldi C, Heltke J, Ng E, Wheeler J, Alfajaro MM, Levavasseur E, Fontes B, Ravindra NG, Van Dijk D, Mane S, Gunel M, Ring A, Jaffar Kazmi SA, Zhang K, Wilen CB, Horvath TL, Plu I, Haik S, Thomas JL, Louvi A, Farhadian SF, Huttner A, Seilhean D, Renier N, Bilguvar K, Iwasaki A.bioRxiv. 2020 Sep 8:2020.06.25.169946. doi: 10.1101/2020.06.25.169946