Focus Area: Research

In Wisconsin, Alzheimer’s disease (AD) is the fifth leading cause of death among those aged 65 and older. Despite decades of research, the etiology of dementia due to AD remains unknown, and there are currently no preventative or disease-modifying treatments available. The overarching goal of this project was to determine the role of the gut microbiome in AD and identify new treatment targets for the disease. This project was successful in identifying new relationships between gut and brain pathology in AD, defining how timing of microbial colonization influences the development of AD, and determining the role microbe-related metabolites may play in preclinical cognitive decline.

As schools reopened and extracurricular activities resumed in the fall of 2021, it was anticipated that the coming respiratory season would be characterized by numerous respiratory infections, some caused by SARS-CoV-2 and others caused by more typical respiratory viruses including rhinovirus, respiratory syncytial virus, and influenza. Schools needed to develop a strategy to quickly distinguish between cases of COVID-19 caused by SARS-CoV-2 and cases of more typical respiratory viruses. The Department of Health Services in Wisconsin developed testing options for K-12 schools which included the use of BinaxNOW Antigen Self-Tests for individuals with symptoms followed by confirmation through PCR for those who were antigen negative. The goal of this project was to identify ways to improve upon the statewide testing by comparing the results of repeated at-home antigen tests to at-school PCR tests and evaluating whether oral “lollipop” swabs were as effective as nasal swabs for identifying children with COVID-19. The results of this project suggest that the at-home BinaxNOW test was at least as sensitive as the nasal PCR test. Additionally, lollipop samples performed better than the nasal swabs and were preferred by 92 percent of students.

COVID-19 presents with non-specific symptoms that are very similar to other viral illnesses, making it difficult to clinically diagnose. Early in the pandemic, polymerase chain reaction (RT-PCR) testing and x-ray computed tomography (CT) were the primary methods of diagnosis, but they lacked effectiveness. The goal of this project was to develop and deploy an artificial intelligence (AI) solution to assist physicians in achieving rapid and efficient diagnosis of COVID-19 using chest x-ray radiography (CXR). Researchers were successful in curating a large COVID CXR dataset and ultimately developed an artificial intelligence (AI) solution that could differentiate between COVID-19 pneumonia and non-COVID-19 pneumonia with high sensitivity and specificity. In the future, this dataset will be used to address key challenges in AI including generalizability, interpretability, and algorithmic bias.

The overuse and misuse of antibiotics in Wisconsin nursing homes is a public health problem as unnecessary prescriptions can lead to antibiotic resistance. This project’s goal was to improve the quality and safety of antibiotic prescribing in Wisconsin nursing homes. By partnering with Wisconsin nursing homes, and the Wisconsin Department of Health Services, the grant team is supporting the implementation and dissemination of an intervention of a urinary tract infection (UTI) toolkit, to promote antibiotic stewardship in nursing homes.

When this project began, the COVID-19 pandemic required the development of vaccines to mitigate the impact of this virus. Whole inactivated vaccines are easy to produce and have been shown to be effective for several viruses including corona, influenza, and Ebola. Thus, the research team proposed to generate a whole inactivated SARS-CoV-2 vaccine virus and test its ability to protect against COVID-19 in an animal model of Syrian hamsters. The research team determined that the inactivated vaccine virus elicited a protective immune response in a hamster model of SARS-CoV-2 infection. The vaccine alone without Quil-A® gave protection two weeks after a second vaccination, even against emerging variants. Although the durability of this inactivated vaccine is currently unknown, the addition of an immune response enhancing substance like Quil-A may extend its protective efficacy.

This project aimed to address the unmet needs of current COVID-19 testing by developing novel molecules called monoclonal antibodies that act to restore, enhance, or mimic the immune system’s attack on the COVID-19 virus. The researchers successfully developed monoclonal antibodies that block viral entry into cells. In the future, these molecules can be incorporated into tests and contribute to therapies for COVID-19.

The prevalence of allergic diseases is increasing worldwide, but little progress has been made in preventing them. Epidemiologic studies have identified strong associations between early life farming exposures and protection from developing allergic diseases. This project aimed to better define the important environmental exposures and immune signatures in providing protection from developing allergic disease. This project established a novel birth cohort including infants born into animal farming environments and traditional old world agrarian lifestyles. Researchers identified key differences between the immune cells and microbial communities of infants that were related to farming lifestyles. These findings are now being leveraged and integrated into a more expansive, NIH-funded project designed to build upon these research findings.

Healthcare workers caring for COVID-19 patients are at high risk of contracting and spreading the virus. Early in the pandemic, there was an urgent need for effective, safe, and easily implementable strategies to reduce the spread of COVID-19. Researchers aimed to evaluate the feasibility of and effects of decontamination interventions including nasal solution and an oral mouthwash on virologic shedding, transmission, and infection outcomes in healthcare workers involved in COVID-19 patient care. Researchers were successful in completing this project. Participants reported high acceptability of the interventions and 73 percent of respondents were willing to use the interventions moving forward.

This project sought to address problems in COVID-19 preparedness to reduce morbidity and mortality and to achieve the highest level of health for all people of Wisconsin. To do this, the research team created a biorepository to support research at the UW and beyond. They also evaluated the persistence of anti-SARS-CoV-2 antibodies. The resulting biorepository contains extensive clinical data, serum, plasma, and immune cells collected over the course of a year from 120 subjects who recovered from COVID-19. In addition to supporting the research of multiple scientists at UW and nationally, the biorepository allowed the research team to demonstrate the presence of antibodies against the SARS-CoV-2 membrane protein in the human body for at least one year, and showed that antibodies that bind to the receptor binding domain (RBD) of the SARS-CoV-2 spike protein are a long-lasting, sensitive, and specific marker of both past infection and vaccination. Thus, the researchers determined that a combination of these antibodies can accurately differentiate between distant COVID-19 infection, vaccination, and naïve states to advance public health, individual healthcare, and research goals.

This project, led by Dr. Ivan Rosado Mendez, aimed to develop and implement ultrasound microvessel imaging (UMI) as a functional imaging technique to study cervical remodeling during pregnancy in real time. Cervical remodeling describes the progressive changes of the cervix during pregnancy and involves four phases: softening, ripening, dilation and postpartum repair. If the cervix ripens in preparation for delivery too early, it can cause premature birth. Preterm birth (PTB), defined as delivery before 37 weeks of pregnancy, results in one million deaths worldwide and is associated with significant racial and socioeconomic disparities. The researchers successfully developed a cervical tissue-mimicking model, called a phantom, composed of agar-based simulated tissue, fluid-carrying channels, blood-mimicking fluid and a system to control fluid dynamics. They validated channel dimensions with micro-CT scans, ensured stability over 14 days and selected a fluid that best matched the features of human blood for the prototype. Finally, the team implemented a high-resolution imaging protocol that was able to detect fluid movement through the channels even when surrounded by simulated tissue.