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Spring 2022 Carver Trust pilot grants fund further COVID-19 studies

Date: Monday, June 6, 2022

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University of Iowa Carver College of Medicine investigators have received research pilot grants as part of a COVID-19 research program funded by the Roy J. Carver Charitable Trust

The pilot grants will fund four new research projects and renew funding for three existing projects. The projects aim to advance the understanding of fundamental aspects and biology of the novel coronavirus (SARS-CoV-2). One of the goals of the pilot grant program is to develop new knowledge that will lead to future studies related to COVID-19.  

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. A recent additional $1 million gift was awarded from the Trust to augment funding toward this basic research. Individual lab projects are awarded up to $50,000; teams of two or more investigators may receive up to $75,000. The total amount awarded in this round is $493,464. 

An initial round of pilot grants for eight research projects was announced in early 2021.

New projects funded:

COVID-19 associated thrombo-inflammation and stroke

Anil Chauhan, MTech, PhD, Department of Internal Medicine; and Stanley Perlman, MD, PhD, Department of Microbiology and Immunology 

The incidence of thrombosis in COVID-19 intensive care unit patients is ~20-30%, but the characteristics of COVID-19 associated coagulopathy are distinct from other sources of coagulopathy. COVID-19 associated coagulopathy is also linked to acute ischemic stroke. This project will delineate the link between thrombo-inflammation and stroke in patients diagnosed with COVID-19 by exploring its pathogenesis at the molecular and cellular level with the goal of testing therapeutic interventions to reduce the mortality rate of these conditions.

Alcohol as a risk factor for SARS-CoV-2 neuroinvasion

Catherine Marcinkiewcz, PhD, Department of Neuroscience and Pharmacology; and Stanley Perlman, MD, PhD, Department of Microbiology and Immunology 

SARS-CoV-2 uses two proteins, angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2), to infect cells. These proteins may be up-regulated by chronic alcohol consumption and could explain the increased risk of severe COVID-19. Marcinkiewcz’s team will investigate how alcohol exposure may promote SARS-CoV-2 neuroinvasion, leading to more severe disease.

Role of complement activation in the pathogenesis of COVID-19

Paul McCray, MD, Stead Family Department of Pediatrics; and Richard Smith, MD, Department of Otolaryngology 

Prior studies of severe COVID-19 cases have implicated the complement cascade, a function of the immune system, as a possible driver of some of the disease’s more life-threatening symptoms. McCray and Smith are studying the role of complement activation in COVID-19 and other respiratory diseases to define the mechanism and establish the utility of complement inhibition as a treatment option.

The role of ME1 during SARS-CoV-2 infection

Lilliana Radoshevich, PhD, Department of Microbiology and Immunology; and Eric Taylor, PhD, Department of Molecular Physiology and Biophysics 

Radoshevich’s team has previously used machine learning to identify a protein (ME1) that may be able to predict COVID-19 mortality. ME1 generates NADPH and is associated with metabolism and the Nrf2 inflammatory pathway. Nrf2 is an emerging regulator of cellular resistance to oxidants. This new study seeks to determine if the protein renders cells and animals susceptible to SARS-CoV-2 infection and if it can be leveraged as a biomarker of severe COVID-19. 

Projects awarded renewed funding:

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

Jon Houtman, PhD, Department of Microbiology and Immunology; and Jack Stapleton, MD, Department of Internal Medicine 

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.

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

Al Klingelhutz, PhD, and Balaji Manicassamy, 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 and 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 next round of the application process will occur in the fall. For more information, contact Erin Brothers, research administrator in the Carver College of Medicine, at erin-brothers@uiowa.edu