Focus Area: Research

Most older women in Wisconsin experience incontinence, which impacts quality of life, but they may not seek care due to stigma. The “Mind over Matter: Healthy Bowels, Healthy Bladder (MOM)” workshop teaches women skills to improve symptoms without a medical professional. Participants in the MOM workshop reported significant improvement in both bladder and bowel symptoms. Since the trial, more than a dozen additional MOM workshops have taken place and more widespread workshops and trainings are planned for 2020, in partnership with the Wisconsin Institute for Healthy Aging (www.wihealthyaging.org).

SARS-CoV-2, the virus that causes COVID-19, genetically changes across populations at a predictable rate of one mutation approximately every 15 days. Understanding the transmission of COVID-19 in healthcare facilities, which are at the core of the pandemic in Wisconsin, is crucial to help resolve the directionality and source of infection. In order to understand if healthcare workers are becoming infected through patient contact, the research team used information such as viral lineage and consensus sequence provided by Oxford Nanopore Technology. The researchers had an initial goal of sequencing ten transmission clusters per month from UW Hospitals and Clinics. They far surpassed this goal and have investigated 55 transmission clusters involving over 400 individuals. After identifying likely and unlikely sources of infection in healthcare workers (HCW) and comparing patient sequences to local outbreaks, they found little evidence for widespread transmission, suggesting that HCWs are most likely to become infected with SARS-CoV-2 in the community.

This project aimed to genetically characterize SARS-CoV-2 in Wisconsin to estimate infection parameters and evaluate the effectiveness of interventions. In March 2020, little was known regarding the true extent of SARS-CoV-2 transmission in Wisconsin. Researchers used genomic surveillance, tracking of different SARS-CoV-2 strains through space and time, to inform decisions on public health measures and aid the transition between mitigation and containment strategies. Preparing the genetic epidemiology infrastructure was crucial for tracking the local SARS-CoV-2 epidemic through 2020. The project was successful in understanding and tracking SARS-CoV-2 transmission in Wisconsin. The team utilized genomic surveillance to identify patterns in SARS-CoV-2 transmission and sequenced over 5,000 viral genomes. The establishment of a sequencing program played a vital role during the emergence of the Delta variant, contributing to its early detection in Wisconsin. This project was also one of the first to show that vaccinated people who became infected with Delta variants could transmit the virus to others. Results from this project established a vigorous new research program that attracted significant extramural support, including three new CDC-funded projects using SARS-CoV-2 genome sequences to reveal patterns in virus transmission and evolution.

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.

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.

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.

This project, led by Dr. Yun Liang, aimed to understand how factors like diet and biological differences between men and women influence autoimmune diseases. Autoimmune diseases like lupus are much more common in women, while men are more often affected by infections and cancer. These sex differences in immune response are not well understood, partly because women have historically been underrepresented in medical research. One promising area of research focuses on a molecule called VGLL3, which is found at higher levels in women and is linked to autoimmunity. The project made significant strides in understanding how VGLL3 contributes to lupus inflammation. High levels of VGLL3 were found to increase the activity of specific lupus-related genes, and high levels of another molecule, called IL17C, suggest a link between VGLL3 and IL17C in driving inflammation in lupus. The study revealed a complex interplay between VGLL3 and immune regulation pathways, especially under conditions of stress. Overall, these findings offer valuable insights into potential therapeutic approaches for lupus.

The Medical College of Wisconsin (MCW) and the UW School of Medicine and Public Health are partnering on an initiative to improve health equity in Wisconsin. MCW’s Advancing a Healthier Wisconsin Endowment (AHW) and the UW’s Wisconsin Partnership Program (WPP), statewide health funders based at Wisconsin’s two medical schools, have announced a joint three-year, $3 million grant to launch an expansive new statewide partnership that will study, measure and recommend solutions for health inequities across the state of Wisconsin.

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.