Focus Area: Research

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.

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.

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.

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.

Karla Ausderau, PhD, assistant professor, UW–Madison School of Education, Department of Kinesiology used a COVID-19 Response grant to address significant health disparities and marginalization experienced by people with intellectual and developmental disabilities (IDD) that have been exacerbated by the COVID-19 pandemic. This project examined the impact of COVID-19 on the health and wellbeing of people with IDD, evaluated current responses to address this impact and provided recommendations to guide service delivery to better meet the needs of this often-underserved population.

This project, led by Matthew Harer, MD, associate professor, Department of Pediatrics, aimed to enhance early acute kidney injury (AKI) diagnosis in premature infants via non-invasive methods. AKI is prevalent among premature infants and it significantly increases mortality and poses a risk of chronic kidney disease (CKD) later in life. In Wisconsin, about 800 extremely premature infants are born each year, with up to 400 experiencing AKI and approximately 100 potentially developing CKD by ages two to five years old. As a result, there is a need for novel diagnostic methods to identify AKI in the NICU. The research team made significant progress toward its goals of enhancing early AKI diagnosis and developing effective therapies. They found that infants with AKI experienced prolonged periods of kidney hypoxia and that administering caffeine improved kidney oxygen levels. Additionally, urinary biomarker analysis identified distinct metabolite profiles associated with AKI, suggesting potential for early diagnosis and intervention in preterm infants to avoid chronic kidney disease. More research is needed, but these findings laid a foundation for improving care and outcomes for premature infants at risk of AKI.