Focus Area: Research

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 is using 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 will elucidate the impact of COVID-19 on the health and wellbeing of people with IDD, evaluate current responses to address this impact and provide 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.

Carey Gleason, PhD, associate professor, Department of Medicine, and co-principal investigators Maria Mora Pinzon, MD, MS, assistant scientist, Department of Medicine, and Melissa Metoxen, senior student services coordinator at the Native American Center for Health Professions were awarded a COVID-19 Response grant for utilizing social media and community advocates to address health consequences of COVID-19 in Black, Latinx and American Indian communities. The overarching goal of this project is to continue disseminating accurate information created by community advocates through social media about COVID-19 and evaluate the effectiveness of social media messages on changing beliefs, attitudes, and adoption of behaviors related to COVID-19 and vaccination.

This project, Defining and Targeting Novel Anti-viral and Anti-cancer T cell Immunity, investigated the role of nuclear-to-cytoplasmic (N→C NF-κB) signaling in regulating CD8+ T cell responses to infections and cancer. The researchers aimed to understand how N→C NF-κB signaling affects CD8+ cell regulation during viral infections and tumor responses. They found that inhibiting the N→C NF-κB pathway led to improved anti-tumor responses in their mouse model, NEMODK. However, in chronic viral infections, the model had reduced virus control, suggesting its importance in CD8+ T cell differentiation. The research team explored a drug that targeted the NF-κB pathway and showed promising results in tumor regression. The study has received NIH funding to further investigate the mechanisms of a NF-κB inhibitory drug.

Humans rely heavily on vision, primarily facilitated by cone photoreceptors in the macula, which provide high-definition spatial and chromatic resolution. Macular degeneration, a leading cause of blindness, affects about 20 percent of people over 45 in Wisconsin. Recent advances in human pluripotent stem cell (hPSC) engineering have made it possible to create 3D retinal organoids (ROs) that mimic the retina’s structure but have yet to demonstrate the phototransduction needed for vision. The goal of this project was to demonstrate that cone cells in lab-grown ROs can respond to light like those in a healthy human eye and test gene therapies to restore vision in patients with achromatopsia. The researchers found that cells in lab-grown ROs had slower and less sensitive responses compared to those in mature primate eyes and confirmed the immaturity of the ROs through 3D mapping of cell connections. The lack of a retinal pigment epithelial (RPE) layer, essential for recycling vision pigments, resulted in limited light sensitivity, but adding artificial pigments improved the cells’ response to light. Using stem cells from achromatopsia patients, the team created ROs that mimicked the condition and they are now testing nanoinjection for delivery of gene therapy after unsuccessful attempts with viral vectors. Overall, this project has made significant strides in understanding and improving lab-grown retinal cells’ function.

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.