Grant Program: Collaborative Health Sciences Program

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.

This project, led by Jacques Galipaeu, MD, aimed to to generate the data needed to secure Investigative New Drug licenses from the Food and Drug Administration (FDA) to use personalized GIFT4 B cells to treat cancer as part of first-in-human clinical trials at the UW Carbone Cancer Center. Previous work enabled researchers to convert normal mouse B cells to cancer-killing cells by treating them with a synthetic cell-signaling protein called GIFT4, and the resulting cells were able to initiate an anti-tumor immune response even in the absence of defined tumor markers. In this work, researchers tested these GIFT4 B cells in mice with prostate and neuroblastoma tumors to see if the cells could improve the immune system’s ability to fight cancer. The researchers made significant progress toward their goal. They found that B cells, when grown with dendritic cells and exposed to GIFT4 protein, could activate T cells which then target tumors. These findings demonstrated the importance of understanding B cell-dendritic cell interactions to advance cancer vaccine development. Additionally, combining GIFT4 B cells with radiation and immunotherapies improved survival, highlighting the efficacy of multifaceted therapies in targeting cancer. Overall, these results have the potential to enhance cell therapies leading to more effective treatment strategies for cancer in the future.

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.

This project, Leaving Prison and Connecting with Medical Care, aimed​​ to evaluate the impacts of two changes to Wisconsin Medicaid policy on health care access, health outcomes and reincarceration for formerly incarcerated individuals. Incarcerated populations have high rates of hepatitis C virus (HCV) and opioid use disorder (OUD), and untreated HCV and OUD lead to severe health and social consequences. Medicaid coverage could reduce adverse health outcomes and reincarceration in former prisoners by improving access to treatment. In 2014, Medicaid eligibility was extended to all poor adults, and in 2015, pre-release Medicaid enrollment assistance was introduced within state prisons, though there has been little research done to assess the effects of these changes on criminal justice-impacted individuals. The project successfully achieved its goals, demonstrating that expanded eligibility and pre-release enrollment assistance increased the number of Medicaid applications before and enrollments at the time of release. The policies improved coverage for both the general population and those with histories of substance use, and they were associated with a 2.5 percent decline in reincarcerations and a 5.2 percent increase in employment procurement. Additionally, the changes to Medicaid policy significantly increased the likelihood of outpatient visits post-release for individuals with substance use histories, although overall substance use disorder-related care remained low.

Through a unique partnership between UW–Madison and the Wisconsin Department of Corrections, this study will provide group cognitive processing therapy to prison inmates. The study will also evaluate the impact of the therapy, with the goal of improving mental health and outcomes for prison inmates as well as informing public policy related to mental healthcare in prisons.

This project, Evaluating a Novel Follow-up Intervention to Improve the Delivery of Follow-up Care for Low-Risk Breast Cancer Survivors in Wisconsin, will implement a novel patient-centered intervention, known as REASSURE, to optimize the delivery of follow-up care to early-stage breast cancer survivors who are at low risk of recurrence. Early-stage survivors comprise 60% of Wisconsin’s more than 70,000 breast cancer survivors. This intervention is designed to better prepare and support early-stage breast cancer survivors while also reducing the burden of unnecessary medical visits that are especially difficult for patients who are socioeconomically disadvantaged or reside in rural areas. The study has the potential to advance cancer care more broadly through adaptation to other cancers where frequent follow-up clinic visits have limited benefit.