Salk researchers accelerate, expand COVID-19 research

LA JOLLA–(June 29, 2020) As the COVID-19 pandemic continues across the globe, the Salk Institute joins in efforts to understand the fundamental science behind the novel coronavirus to pave the way to treatments and cures. COVID-19 exploits a vulnerability in the immune system’s armor: because the SARS-CoV-2 virus–the novel coronavirus that causes COVID-19–appeared in humans recently, our immune systems have no experience with the virus–and sometimes have difficulty fighting it.

“It is hard to overstate the impact of COVID-19, the disease caused by the novel coronavirus, on our world,” says Salk President Rusty Gage. “Salk scientists with expertise in virology, immunology and infectious disease are fully engaged pursuing bold research focused on the COVID-19 infection and the SARS-CoV-2 virus that causes it.”

Salk faculty are tackling COVID-19 research from a number of angles, some via ongoing research projects that have direct relevance to the virus, including:

• Professor Janelle Ayres is studying pneumonia and acute respiratory distress syndrome (ARDS, which occurs in COVID-19 patients).
• Professor Greg Lemke is delving into how receptors regulate the immune response and is studying ways to prevent the “cytokine storms” that develop in COVID-19.
• Professor Satchin Panda is focusing on the long-term gene activity in COVID patients.
• Research Professor Marga Behrens is researching the effects of virus-induced maternal immune activity on brain development of offspring.

There is also a host of new, approved COVID-19 research projects underway, including:

• Professor Tony Hunter previously showed that the cytokine LIF (leukemia inhibitory factor) plays a role in pancreatic cancer. In severe COVID-19 cases, immune cells in the infected windpipe and lungs can release high levels of cytokines, damaging inflammatory proteins. He will test whether cytokines, like LIF, play a role in the immune overreaction (“cytokine storm”) seen in some COVID-19 patients.
  • Gerald Pao, a staff scientist in the Hunter lab, will work with the Sanford Burnham Prebys Medical Discovery Institute to generate a virus system that expresses a spike protein that mimics the ones on the coronavirus. The team will then examine the immune response to these spike proteins.
  • In collaboration with UC San Diego, USC and the Sanford Burnham Prebys Medical Discovery Institute, Pao will develop a test to detect the presence of COVID-19 coronavirus genomes in human nose and throat samples. He has designed this test, which will combine CRISPR with an imaging technology, so that it will only take a few minutes.
  • Pao will also engineer CAR-T cells, cells that can target specific proteins, to aid in the development of a coronavirus vaccine. These cells are repurposed from cancer immunotherapy to provide immune surveillance and kill coronavirus-infected lung cells that have a spike protein on their surface, early in the infection.

• Professor Susan Kaech, who studies how we develop immunity to severe viral infections, such as influenza and now COVID-19, will collaborate with The Scripps Research Institute and La Jolla Institute to study the types of memory T and B cells that form in the lung following SARS-CoV-2 infection as a way to understand if and how long-term immunity to SARS-CoV-2 can be established. This work will be critical to understanding the types of memory T cells that COVID-19 vaccines will need to re-create in vaccinated individuals to establish benchmarks for generating protective immunity. Kaech recently published a paper on this topic in the Journal of Experimental Medicine.
  • Creating a protective coronavirus vaccine is currently one of the world’s greatest challenges. Kaech believes that immune cells called memory B and T cells are likely critical for controlling the infection, and could therefore be excellent targets for vaccines to enable long-term immunity. Her lab, in collaboration with The Scripps Research Institute, will examine the role of memory T cells inside the lungs during a COVID-19 infection.
  • In a separate study, in collaboration with pulmonary physicians at UC San Diego and the VA hospital, Kaech
    will examine changes in the levels and composition of surfactant in COVID-19 patients. Surfactant is a substance in the lungs that allows us to breathe. The study will compare surfactant levels with the health outcomes of COVID-19 patients to determine if a drop in surfactants is associated with more severe disease. Her lab will also test if genetic alterations in pathways that control surfactant levels in the lungs alter the course of the disease.

• Assistant Professor Dmitry Lyumkis will examine the molecular mechanisms by which the non-structural protein NSP1 halts host protein production. This process ultimately helps the virus in promoting the production of its own viral proteins and the development of COVID-19. The Lyumkis lab will also explore how the non-structural protein NSP2 affects host cells during the development of COVID-19.
• Professor Juan Carlos Izpisua Belmonte is collaborating with a San Diego biotechnology company to develop COVID-19 treatments using nanoparticles. The researchers will use RNA-targeting CRISPR-Cas technology to destroy the SARS-CoV-2 virus’ RNA. This treatment will prevent the virus from replicating in the body, thereby reducing the severity of an individual’s COVID-19 infection and limiting the virus’ chances of spreading. If successful, this approach could be extended to treat other RNA viruses in the future.
• It will take a virus to kill a virus. Professors Clodagh O’Shea, Alan Saghatelian and Joseph Noel are exploiting the atomic structures of the SARS-CoV-2 virus, together with proprietary synthetic virology and chemical biology platforms, to create transformative vaccines and gene therapies. Their pipeline will target i) SARS-CoV-2 prevention by creating synthetic live viral vaccines that induce broad and long-lasting immunity and ii) SARS-CoV-2 treatment through viral gene therapies that express synthetic nanoparticles that seek, neutralize and destroy SARS-CoV-2 and prevent pathology. This research will uncover underlying principles and overcome intractable clinical challenges, not just of SARS-CoV-2 today, but of SARS-CoV-3 tomorrow.

“The foundational basic research underway at Salk plays a central role in shaping our approach in response to COVID-19, and to prevent similar crises in the future,” says Salk Vice President, Chief Science Officer and Professor Martin Hetzer. “This pandemic has shown how critical basic research is to responding to the greatest health challenges of our time, including infections like COVID-19, diseases of aging like Alzheimer’s, and climate change.”

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