One of the NIH mandates for regional biosafety laboratories is to have the capacity in place to conduct research on pathogens as needs arise, especially in outbreak scenarios. The RBL is working as it was envisioned to work. We offer these services to researchers at Tufts [Cummings School], regionally, and nationally. We have many collaborations ongoing.
Research Published in Science Translational Medicine Highlights Animal Model Studies at Tufts New England Regional Biosafety Lab
Cummings School investigators test drug’s effectiveness in reducing lung disease caused by COVID-19
A new study featured in the biomedical journal Science Translational Medicine this past July is the first published research that showcases the capabilities of Tufts New England Regional Biosafety Laboratory (NERBL) at Cummings School of Veterinary Medicine at Tufts University to conduct COVID-19 research .
“This manuscript demonstrates that we have these animal models up and running at Tufts to use for various purposes. We are ready and capable of running studies for other researchers,” says Dr. Amanda Martinot, who led the research project in the NERBL. Martinot is co-director of the Comparative Pathology and Genomics Shared Resource, veterinary anatomic pathologist in the Department of Comparative Pathobiology, and E.A. Stevens Associate Professor in the Department of Infectious Disease & Global Health at Cummings School.
Tufts New England Regional Biosafety Lab is one of 12 similar regional laboratories in the United States funded by the National Institute of Health (NIH) for pathogen readiness. The lab is equipped with the added capacity to conduct animal model studies to support research into the detection, prevention, and treatment of infectious diseases. SARS-CoV-2, the virus that causes COVID-19, can only be studied in specialized laboratories like the NERBL, that have heightened safety and biocontainment practices. This is why the ability to conduct animal model studies in these facilities is so important.
The capacity to run SARS-CoV-2 animal model studies in NERBL came about from the efforts of Martinot and her colleagues at Cummings School. Dr. Sally Robinson, associate director for research operations at the RBL, secured the foundational seed funding from Tufts Office of the Vice Provost for Research to establish the animal model studies with Dr. Saul Tzipori, professor in the Department of Infectious Disease & Global Health, Agnes Varis University Chair in Science and Society of the Provost’s Office, and Distinguished Professor at Cummings School. Martinot and Tzipori spearheaded efforts to gain funding from the NIH to apply specialized digital image analysis to help interpret results from the studies.
“It’s been a huge effort across the university. We aggressively went for funding resources to get SARS-CoV-2 animal models validated for use at Tufts,” says Martinot. “One of the NIH mandates is to have the capacity in place to conduct research on pathogens as needs arise, especially in outbreak scenarios. The NERBL is working as it was envisioned to work. We offer these services to researchers at Tufts, regionally, and nationally. We have many collaborations ongoing.”
Robinson adds, “We have a strong commitment at the NERBL to be a regional resource for scientists in infectious disease research. Our team at the NERBL offers services to researchers including biocontainment training and provides expertise working with animal models and assays for infectious disease. We are available to support research programs as well as form ongoing scientific collaborations.”
“When the pandemic occurred, researchers were trying to create vaccines and required facilities capable of using animal models. With all the resources we put together here at Tufts [Cummings School], we were able to provide that resource to them,” says Martinot. In 2020, researchers from the University of California San Diego (UCSD) were the first to tap into Cummings School’s new capacity to conduct COVID-19 research utilizing animal models.
The UCSD researchers hypothesized that a new cancer drug candidate would also be effective against lung inflammation caused by SARS and other viruses. Martinot explains that the drug was developed as a host-directed therapy for cancer, as many of these types of drugs were being repurposed to treat COVID-19.
The purpose of the UCSD study was to test a potential therapy for reducing the inflammatory lung damage caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) and other viral inflammatory diseases. Dr. Martinot explains that these viruses often lead to interstitial pneumonia, in which inflammatory myeloid cells (macrophages, neutrophils, and monocytes) enter spaces between the airways and can cause those airspaces in the lungs to collapse. This new drug would target myeloid cells with P13Kγ inhibitors, previously shown to be effective in cancer studies in suppressing inflammation.
Martinot and her team are co-authors on the manuscript, titled “P13Kγ inhibition circumvents inflammation and vascular leak in SARS-CoV-2 and other infections,” and wrote the portion of the manuscript pertaining to the hamster studies conducted in the NERBL.
“It’s the first major therapeutic study where we used the hamster model,” says Martinot. “We showed that the drug did have an effect on inflammatory infiltrates and improved outcomes in those hamsters.”
The team at Cummings School found that the drug did prevent the recruitment of myeloid cells, in line with the study’s finding with mice and human specimens, that P13Kγ inhibitors did help against SARS-CoV-2, and may be effective in treating inflammatory lung disease in humans.
“The animal models are one piece of scientific evidence that the drug is working as predicted,” says Martinot. “This particular drug serves as a proof of principle that repurposing existing drugs, such as cancer drugs, can potentially be of use for COVID treatment.”
Martinot’s team wrapped up their portion of the research for UCSD in 2021 and have been working on a number of other research projects related to SARS-CoV-2, including a current collaboration with Tufts University School of Medicine researchers (Dr. Pilar Alcaide and Dr. Iris Jaffe) and with Boston University as part of the Massachusetts Consortium on Pathogen Readiness (MassCPR) Pathobiology group focused on long COVID. Martinot and Tzipori also co-mentor a graduate student whose work is focused on using the mouse model for SARS-CoV-2 research and to understand the pathogenesis of long COVID (see story here).
“We’re all very proud we managed to make this happen, to showcase what we can do, and get the model and data published in a peer-reviewed, high caliber journal like Science Translational Medicine,” says Martinot. “It’s a huge feather in the cap for our facility and research team.”