In the midst of a worldwide pandemic, UCSF is dedicating many of our research studies towards combating COVID-19. Read about the many COVID-19 related research studies below.
Under leadership from Pulmonary Division physician-scientists at UCSF and ZSFG the COMET Study (COVID-19 Multi-Phenotyping for Effective Therapies) has enlisted an interdisciplinary team of scientists and frontline healthcare workers to study COVID-19. The purpose of this study is to better understand how it affects the immune system, why it causes difficulty breathing, and why some people become sicker than others. Learn more about the study at the COMET Study official website and the COMET Study page on this site.
Other COVID-19 Related Research
The Bhattacharya lab studies lung macrophages in acute and chronic inflammation. For COVID19, we have been interested in boosting antiviral type 1 interferon responses by these first-responder cells through the use of TLR agonists, which we are testing in mouse and human models. Several TLR agonists are under clinical development for other indications and could be tested in early COVID19 infection if we can provide rationale from our preclinical studies.
The Gordon lab is studying the basic mechanisms of SARS-CoV2 virulence using human airway epithelial cells. Our hypothesis is that a key virulence factor in the SAR-CoV-2 virus, the E protein, triggers IL-1B secretion from epithelial cells in a gasdermin and caspase dependent manner. IL-1 secretion acts in an autocrine fashion, to inhibit critical interferon responses that are required to constrain the virus to the upper airway and prevent lower airway infection. We are examining these effects in cells from old and young individuals and using CRISPR-Cas9 to determine the basis for cytokine secretion. We are testing novel therapeutics that target these pathways.
The Greenland lab is investigating novel therapies for COVID-19. With excess tissue obtained at the time of lung transplantation, we are using epithelial air liquid interface culture models to study therapies that may inhibit infection, cell injury, and cytokine storm
The Reiter lab in the Department of Biochemistry and Biophysics is mapping SAR-CoV-2 infection, replication and transcriptional responses in human airway epithelial cells in collaboration with several other groups here at UCSF. In addition, they are investigating whether a nonstructural protein produced by SARS-CoV-2, NSP13, interacts with centrosomal proteins to control viral replication.
The Sheppard Lab is currently working on two COVID-19 related studies. The first involves trying to understand why severe pulmonary effects are delayed and how alveolar, epithelial cells, which normally express low or non-existent levels of the well-established receptor, ACE2, get infected to cause pulmonary pathology. We are testing the hypothesis that anti-SARS CoV2 antibodies may play a crucial role by binding to the virus and facilitating uptake into the epithelial cells by binding to the neonatal Fc receptor (FcRn), a mechanism that might be facilitated by the low pH of the alveolar lining fluid.
The other study involves helping to plan a clinical trial of a drug we have developed together with Pliant Therapeutics, that blocks the alphavbeta6 integrin. We and others have previously shown that inhibition of this integrin can prevent or reverse alveolar flooding in acute lung injury and that inhibition of this integrin also accelerates viral clearance in models of influenza pneumonia. The drug is currently in phase clinical trials for treatment of pulmonary fibrosis and primary sclerosing cholangitis and we are working with the FDA to allow enrollment of patients with hypoxic respiratory failure from COVID-19 for treatment with this orally available drug beginning in September, 2020.