Carver Trust pilot grants spur COVID-19 studies

Date: Tuesday, June 29, 2021

Coronavirus with a dark backgroundUniversity 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 five research projects that aim to advance the 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. Individual lab projects are awarded up to $50,000 in pilot project funding; teams of two or more investigators may receive up to $75,000.

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

Following are latest projects funded by the Carver Trust pilot grant program:

Unraveling the role of saliva in COVID-19 pathogenesis using a comprehensive multi-omics approach

Ashutosh Mangalam, PhD, Department of Pathology; Eric Taylor, PhD, Department of Molecular Physiology and Biophysics; Sukirth Ganesan, PhD, UI College of Dentistry; and Kevin Legge, PhD, Department of Pathology

With the emerging evidence on the significant role of COVID-19 transmission and infection, the goal of this pilot grant is to identify the microbial, immune, and metabolic biomarkers/signatures of COVID-19 in saliva. To further the understanding of pathogenesis of this pandemic, the multidisciplinary team has been assembled spanning across the fields of microbiome, oral biology, metabolomics, viral immunology, and infectious disease. In addition to the investigators listed above, Val Sheffield, MD, PhD, Stead Family Department of Pediatrics, and Katherine Imborek, MD, Department of Family Medicine, will serve as study consultants.

Metabolic imaging neurological post-COVID-19 fatigue using F-18 positron emission tomography

Eunkyung Park, MD, PhD, and Laura Ponto, PhD, Department of Radiology; and Thorsten Rudroff, PhD, Department of Health and Human Physiology, UI College of Liberal Arts and Sciences

For survivors of severe COVID-19 infection, overcoming the virus is just the beginning of an uncharted recovery path. Recent reports indicate that groups of patients experience persistent symptoms even after recovery from the acute phase of the disease. Park and colleagues are particularly interested in enduring post-COVID-19 fatigue that adversely affects people’s quality of life and undermines daily functioning. The first step in finding a treatment solution is to better understand the underlying neural mechanism. The research team will investigate if such fatigue is associated with changes in the brain metabolism by using a functional neuromolecular imaging technique called positron emission tomography.

The role of IL-13-induced airway goblet cell metaplasia in host responses to SARS-CoV-2

Alejandro Pezzulo, MD, Department of Internal Medicine; and Paul McCray, MD, Stead Family Department of Pediatrics

The allergic type of inflammation present in half of people with asthma may either protect the lungs or increase damage from SARS-CoV-2 infection. Pezzulo and McCray will test the effects of allergic inflammation in primary human airway cells in vitro or in mice in vivo and how it affects infection by SARS-CoV-2. This collaboration between the Pezzulo and McCray labs will leverage their complementary expertise in genomics, virology, and epithelial biology to understand the basis of an important clinical question.

Structural mechanisms and targeting of the SARS-CoV-2 replication

Maria Spies, PhD, Department of Biochemistry

The Spies lab will investigate a detailed 3-D structure of a large SARS-CoV-2 protein called Nsp3 (non-structural protein 3). This protein contains modules that interact with RNA, process viral proteins, and strip human proteins of specific signaling marks. It also contains a module, called SARS unique domain, which is found in SARS, but not in other related coronaviruses. While structures of some of the Nsp3 modules have been determined, the research team will learn, for the first time, how these modules come together to assist viral replication. Knowledge of the Nsp3 architecture and Nsp3 preference for specific RNA will explain the involvement of the Nsp3 in SARS replication/transcription and suggest novel therapeutic targets.

The role of SAMHD1 in regulating SARS-CoV-2-induced inflammation

Li Wu, PhD, Wendy Maury, PhD, and Lilliana Radoshevich, PhD, Department of Microbiology and Immunology; and Patrick Sinn, PhD, Stead Family Department of Pediatrics

To better combat the COVID-19 pandemic, improved fundamental knowledge of severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) is needed, including studies to characterize viral replication and transmission and to understand host immunity. Wu and colleagues aim to investigate the role of a unique cellular enzyme called SAMHD1 in regulating SARS-CoV-2 replication and virus-induced inflammation. This basic study is important to better understand the host responses to SARS-CoV-2 infection and the mechanisms of immunoregulation of COVID-19.