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Researchers awarded COVID-19 pilot grants from the Carver Trust

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Date: Friday, January 29, 2021

Twelve University of Iowa Carver College of Medicine faculty have received pilot grants from the Roy J. Carver Charitable Trust as part of a new COVID-19 research program.

The pilot grants will fund eight research projects that aim to advance the fundamental aspects and biology of the novel coronavirus known as SARS-CoV-2. One of the goals of the pilot grant program is to develop new knowledge that will serve as the foundation for future COVID-19 studies that merit extramural funding.

The pilot grant program was established in fall 2020 with the support of a $1 million gift from Carver Charitable Trust through the UI Center for Advancement. Individual lab projects may be awarded up to $50,000 in pilot project funding; collaborating teams of two or more investigators may receive up to $75,000.

“Basic science research is key to understanding living systems at the cellular and molecular levels, which can lead to better ways to predict, prevent, diagnose, and treat diseases such as COVID-19,” says Patricia Winokur, MD, executive dean of the UI Carver College of Medicine. “Thanks to the generosity and vision of the Carver Trust, our research teams can make high-impact contributions to a growing body of COVID-19 studies.”

“The SARS-CoV-2 virus and its mutant variants are likely to persist as serious threats in our communities for the foreseeable future, so efforts seeking a more complete understanding of their biology and physiological effects remain absolutely critical areas of scientific inquiry,” says Troy Ross, PhD, CEO of the Carver Charitable Trust. “Supporting these studies with strategic and flexible funding reflects the Carver Trust’s dedication to responsible philanthropy that positively impacts, protects, and improves human health.”

Following are the first round of funded projects under the Carver pilot grant program:

Mechanisms of CD40-mediated early protection from SARS-CoV-2 infection

Gail Bishop, PhD, and Wendy Maury, PhD, Department of Microbiology and Immunology

Much remains to be learned about the immune response to the coronavirus SARS-CoV-2 responsible for the COVID-19 pandemic. Bishop and colleagues recently discovered that early SARS-CoV-2 infection of lung cells induces rapid antiviral immune responses mediated by a specific immune stimulatory protein called CD40, expressed by the lung cells. This project will investigate the characteristics and mechanisms of this antiviral response to better understand, and possibly therapeutically harness, immune defenses against SARS-CoV-2.

Hypercoagulability in a novel mouse model of SARS-CoV-2 infection

Sanjana Dayal, PhD, and Steven Lentz, MD, PhD, Department of Internal Medicine­, Division of Hematology, Oncology, and Blood and Marrow Transplantation

Patients with COVID-19 tend to develop clots in blood vessels, often leading to death. However, the reasons why people with COVID-19 develop blood-clots are not fully known. A newly developed mouse model by Stanley Perlman, MD, PhD, UI professor of microbiology and immunology, and colleagues mimics human COVID-19 disease and also exhibits small clots in the lung. Using this model, Dayal and colleagues will study whether and how the protein IL6, which is found to be increased in human and mouse COVID-19 models, causes blood clot formation during SARS-CoV-2 infection. The team plans to expand studies in the future to incorporate other risk factors such as aging, diabetes, kidney failure, and high blood pressure using this model.

Neuropathological assessment of COVID-19-related neurodegeneration

Marco Hefti, MD, Department of Pathology, and Li-Chun (Queena) Lin, PhD, Department of Neuroscience and Pharmacology

The purpose of this project is to understand how COVID-19 infection—and the often long hospital and ICU stays that patients often have as a result—affects the brain. This includes both immediate effects of COVID-19 on the brain and long-term effects on patients who have recovered. Hefti and colleagues are particularly interested in the relationship between COVID-19 and neurodegenerative diseases such as Alzheimer’s disease.

Investigating the dysregulation of TCR signaling and CD4 T cell differentiation by SARS-COV-2 protein trimer

Jon Houtman, PhD, Department of Microbiology and Immunology, and Jack Stapleton, MD, Department of Internal Medicine, Division of Infectious Diseases

This project will help researchers better understand how proteins on the outside of the COVID-19 virus change the ability of white blood cells to react to the infection. These studies will highlight a new way the COVID-19 virus changes the immune response, which will aid in designing better therapies and vaccines for the virus.

Cellular and molecular mechanism underlying nasal viral priming-induced innate immunity in the lungs

Xiaoyang Hua, MD, Department of Otolaryngology–Head and Neck Surgery

Epidemic and pandemic lethal viral pneumonia periodically occur, resulting in substantial morbidity, mortality, and socioeconomic impact. Hua’s recent research suggests that targeting the nasal mucosa—the type of tissue that lines the nasal cavity—can induce broad spectrum immunity in the lungs against lethal respiratory virus infections. This project aims to further define this protective mechanism and develop new preventive and therapeutic strategies to combat lethal respiratory virus infection, including COVID-19.

The role of visceral fat in SARS-COV-2 infection

Al Klingelhutz, PhD, and Wendy Maury, PhD, Department of Microbiology and Immunology

Obesity significantly increases the possibility of severe symptoms, hospitalization, and death associated with COVID-19. Obese people accumulate fat through expansion of fat cells, also referred to as adipocytes. Studies have shown that people with a large amount of abdominal fat (visceral fat) are the most prone to complications of COVID-19. Preliminary studies indicate that visceral fat cells can be infected by SARS-CoV-2, the cause of COVID-19. This suggests the intriguing possibility that one reason for the severity of COVID-19 in obese patients is that the virus is infecting abdominal fat cells, causing them to become inflammatory and non-functional. Klingelhutz and colleagues will examine the consequences of SARS-CoV-2 infection of visceral fat cells. This will lead to a better understanding of why obesity is so strongly associated with more severe COVID-19 symptoms and may point to novel treatment strategies.”

Viral cell tropism in the pathogenesis of SARS-COV-2

Balaji Manicassamy, PhD, Department of Microbiology and Immunology

SARS-CoV-2 infection of the respiratory tract can cause severe damage beyond the lungs, including the heart and kidneys. The goal of Manicassamy’s study is to determine if SARS-CoV-2 causes severe disease by targeting specific cells in the body and to utilize this knowledge in the development of treatments against COVID-19.

The role of ISGylation in SARS-COV-2 infection

Lilliana Radoshevich, PhD, Department of Microbiology and Immunology

Following an infection, our immune systems detect viral or bacterial pathogens and begin to produce an arsenal of antiviral proteins to protect us from the infection.  However, some viruses like SARS-CoV-2 block this process before it can start using enzymes that cut up host antiviral proteins. Radoshevich’s laboratory studies a host defense protein called ISG15; the goal of this project is to boost its activity prior to viral infection to improve outcomes in COVID-19 patients and in other respiratory viral infections like influenza.  

A second round of the application process will occur in spring 2021. For more information, contact Erin Brothers, research administrator in the Carver College of Medicine, at erin-brothers@uiowa.edu.