Grant Program: Collaborative Health Sciences Program

In Wisconsin, people of Hmong ancestry are infected by a particular fungal lung disease at rates up to 100 times higher than people of European ancestry, a concerning public health disparity. The researchers identified the genetic basis for susceptibility to the fungal infection in people of Hmong ancestry, providing new opportunities for treatment and education.

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.

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.

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.

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.

Emerging and recurring viral infections remain a threat to public health and personal well-being. This innovative project proposes to “rediscover” rheumatoid factor (RF), a naturally occurring autoimmune antibody generally considered a hallmark of rheumatoid arthritis, as a unique, universal antiviral agent. The primary goal of this proposal is to learn more about the role of RFs in COVID-19 in order to inform the development of a universal antiviral treatment for rapid deployment during seasonal, endemic and future viral pandemics. The findings have the potential to inform the development of novel therapeutics for treating wide range of viral infections.

Two incurable cancers, prostate cancer and pediatric neuroblastoma (a cancer often found in the adrenal glands) have high incidence rates in Wisconsin. This study will attempt to treat these cancers with an exciting new therapy approach using B-cells.

Lupus is one of the most common autoimmune diseases, causing lifelong burden for 1.5 million U.S. and 28,000 Wisconsin residents. Currently, gaps in care for people with lupus contribute to more kidney failure, more cases of early death, and greater disease damage. Notably, in the US, those with lupus who are Black suffer greater disease burden when compared to other countries, likely indicating disparities in the U.S. healthcare system. Research shows that similar care gaps, disparities, and negative health consequences experienced by people with HIV were reduced by more than 20 percent through targeting key steps to control the disease: diagnosis, linkage to care, retention in care, retention on therapy and low disease activity/ damage to body. Using cutting-edge gap-closing data analysis methods, Dr. Bartels, Dr. Elwert and team will first study retention in care and retention on immune therapy, and then will further examine gaps and predictors in all five key steps for lupus care to identify which steps offer the most potential to eliminate health disparities and improve outcomes. Healthcare and patient partners will help select, adapt and pilot-test strategies that successfully reduced HIV outcome disparities. The results will provide a foundation for future studies to improve damage-free survival and health equity for people with lupus. This project includes collaborators from UW–Madison and the Medical College of Wisconsin.

Human papillomavirus (HPV) is the most commonly sexually transmitted disease in the United States – an estimated 79 million Americans are currently infected— and the number one risk factor for developing anogenital cancers, such as squamous cell carcinoma of the anus (SCCA). In Wisconsin, HPV-positive SCCA disproportionately affects underserved populations, particularly those living with HIV. Once HPV-driven anal pre-cancers are diagnosed, there are few treatment options that are effective or well-tolerated. This project builds on recent findings that show select FDA-approved protease inhibitors, previously used orally to treat HIV infection, can also be used topically to prevent HPV-associated cancers, in particular SCCA. This team of interdisciplinary researchers will work to determine the molecular mechanisms supporting these effects and repurpose these drugs as an approach for anal cancer prevention in Wisconsin. The long-term goal of this research is to develop a new strategy to prevent HPV-associated cancers, particularly SCCA, especially in high-risk patients such as people living with HIV. This project also includes collaborators from UW–Madison.

Wisconsin’s prison population is faced with high rates of Hepatitis C infection (HCV) and opioid use disorder, both of which have dire consequences if left untreated. Thus, individuals need to be connected to care as they re-enter society, but research is needed to identify effective interventions.