Helping the World Breathe Easier
01 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 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.
02 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 longterm 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.
03 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.
Tiny Treatments, Big Results
01 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.
02 In addition, Izpisua Belmonte led a team of multi-institution scientists to develop a new viral screening test that can not only diagnose COVID-19 in a matter of minutes with a portable, pocket-sized machine, but can also simultaneously test for other viruses—like influenza—that might be mistaken for the coronavirus. At the same time, clinicians can sequence the virus, providing valuable information on the spread of COVID-19 mutations and variants. Read more here»
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A Seek-and-Destroy Mission
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.
Helping Patients Tolerate Serious Infections
Sometimes the body’s immune response causes more damage than the pathogen it is fighting. In these cases, limiting damage and supporting affected organs—such as with drugs that manipulate normal metabolism and repair processes—is paramount. Using her knowledge of physiology and infectious disease, Professor Janelle Ayres studies ways to help patients better tolerate infections, such as pneumonia and the acute respiratory distress syndrome (ARDS) that occurs in COVID-19 patients.
Maintaining a Healthy Balance
Healthy immunity is a fine balance: too strong a response and autoimmune disease or other damage can occur; too weak a response and cancer or infections can take hold. 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, as the body produces such an overwhelming immune response in the lung that the collateral damage can be lethal for patients.
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Averting Cytokine Storms and Designing New Tests and Treatments
01 In severe COVID-19 cases, immune cells in the infected windpipe and lungs can release high levels of damaging inflammatory proteins called cytokines, colloquially known as a “cytokine storm.” American Cancer Society Professor Tony Hunter previously showed that the cytokine LIF (leukemia inhibitory factor) plays a role in pancreatic cancer. He will test whether cytokines, like LIF, play a role in the immune overreaction seen in some COVID-19 patients.
02 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.
03 In collaboration with UC San Diego, USC and Sanford Burnham Prebys Medical Discovery Institute, Pao will develop a test to detect the presence of COVID-19 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.
Halting Viral Production
01 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.
02 The Lyumkis lab will also explore how the nonstructural protein NSP2 affects host cells during the development of COVID-19.
Timing is Everything
Research from the lab of Professor Satchin Panda has found that the majority of our genes follow a day/night rhythm in many tissue types and brain regions. This has implications for many behaviors, including when it’s best to eat, exercise, and take medications. Because COVID-19 affects so many bodily systems, Panda is studying gene activity in COVID patients to see how day-to-day changes in this activity and the clinical symptoms of COVID predict treatment outcomes. The research findings will impact predictions of COVID patients’ disease course when they check in to the hospital and finding the right treatment to accelerate recovery.
Influencing Brain Development
Many more factors than DNA alone influence brain development. These include events that happen both in the womb as well as after birth. Research Professor Margarita Behrens is researching the effects of virus-induced maternal immune activation on brain development of offspring, which, given the number of COVID-19 infections worldwide, could reveal a significant effect.
Understanding the Spike Protein
Scientists have known for a while that SARS-CoV-2’s distinctive “spike” proteins help the virus infect its host by latching on to healthy cells. A new study co-led by Assistant Research Professor Uri Manor and UC San Diego shows that the proteins also play a key role in the disease itself. The study shows conclusively that COVID-19 is a vascular disease, demonstrating exactly how the SARS-CoV-2 virus damages and attacks the vascular system on a cellular level. The findings help explain COVID-19’s wide variety of seemingly unconnected complications, and could open the door for new research into more effective therapies.
