Focus Area: Research

There are 7,000 different rare genetic disorders that impact approximately 450,000 people in Wisconsin. Gene therapy has the potential to treat these diseases if two major limitations can be addressed: better targeting of the therapy agent and affordability. This project, led by Kinjal Majumder, PhD, assistant professor, Department of Oncology, sought to address these limitations by improving the nuclear targeting of gene therapy vectors. The team used a combination of CRISPR/Cas9 technology, Big Data and high-resolution imaging to study the molecular mechanisms of Recombinant Adeno-Associate Virus (rAAV) vectors for gene therapy delivery and provide insights into engineering better rAAV gene therapy vehicles. Their findings will inform future work in the field of gene therapy, with the potential to improve treatments for rare genetic disorders and develop cancer-targeting gene therapies.

Down syndrome, also known as trisomy 21, is a condition that impacts the brain’s development of neurological pathways resulting in mild to moderate intellectual disability and middle age onset of Alzheimer’s disease. Basal forebrain cholinergic neurons (BFCNs) are crucial in mediating cognitive performance and memory throughout the lifespan, and they are particularly susceptible to degeneration in individuals with Down syndrome. This project sought to explore the mechanisms that underlie BFCN vulnerability in Down syndrome and looked specifically for observable and age-related markers of BFCN dysfunction in trisomy 21. The results showed similar levels of Alzheimer’s-related proteins in the BFCNs of individuals with and without Down syndrome, despite the fact that people with the condition have an extra gene copy that produces these proteins. The research team identified that trisomy 21 BFCNs had elevated levels of aging markers which may contribute to the intellectual disability and middle age onset of Alzheimer’s disease in people with the condition.

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.

Despite the pressing need for post-traumatic stress disorder (PTSD) treatment within the jail and prison population, there is virtually no research examining the efficacy of such therapies in incarcerated adults. Researchers at UW – Madison partnered with the Wisconsin Department of Corrections (DOC) to implement and evaluate cognitive processing therapy (CPT) for prison inmates, a promising PTSD intervention due to the cost- and time-effectiveness of its group format. Overall, study data indicated that group CPT in state prisons is feasible, acceptable and effective.

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.

Human papillomavirus (HPV) is the most common sexually transmitted disease in the United States and the number one risk factor for developing anogenital cancers, such as squamous cell carcinoma of the anus (SCCA). Once HPV-driven anal pre-cancers are diagnosed, there are few treatment options that are effective or well-tolerated. This project further explored 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 worked to determine the molecular mechanisms supporting these effects and repurpose these drugs as an approach for anal cancer prevention in Wisconsin.

Gaps in lupus care contribute to higher kidney failure, more early death, and worse lupus damage in U.S. patients who are Black or poor. This project used new data analysis methods to study and identify steps in lupus care with the largest impact on patient health. Health care and patient partners then helped select, adapt, and pilot test strategies to reduce health disparities and improve outcomes.

This project, led by Jacques Galipeau, 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.

This project, led by the UW Population Health Institute, aimed to analyze data relating to Milwaukee County’s rapid dissemination of $77.4 million in COVID-19 relief funding in order to assess investments addressing social determinants of health and racial equity strategies. Milwaukee County was the first municipal government in the country to declare racism a public health crisis and was among the first to collect race and ethnicity data that helped guide efforts to prevent the spread of COVID-19 in communities of color. The project team successfully assessed Milwaukee County’s investments in social determinants of health and racial equity strategies, collaborating with county leaders and analyzing funding data from state claims and federal expense reports. Their analysis showed that Milwaukee County made significant efforts to ensure equity for marginalized populations affected by COVID-19, particularly through the $12 million Small Business Recovery Grant program. This program distributed grant monies to minority, woman and veteran-owned businesses, with 66% of the 1,551 grant recipients falling into these categories. Additionally, the Milwaukee County Department of Administrative Services Economic Development Division created an interactive map to visualize the locations of funded businesses.

Rachel Gicquelais, PhD, MPH, assistant professor, UW–Madison School of Nursing, and co-principal investigator Ryan Westergaard, MD, PhD, MPH, associate professor, Department of Medicine, used a COVID-19 Response grant to address the dual epidemics of COVID-19 and drug overdose. With a focus on rural Wisconsin residents, the goal of this project was to understand patterns of overdose risk, COVID-19 vaccine willingness, and related attitudes and behaviors. Investigators also tested a novel mobile health intervention to support vaccine uptake in people who inject drugs.