Focus Area: Research

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.

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, 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.

This project, led by Dr. Jennifer Weiss, aimed to characterize factors at the system, clinic, provider and patient levels that influence colorectal cancer (CRC) screening rates at rural and urban clinics. CRC is the second leading cause of cancer-related deaths for adults in Wisconsin, and it the most preventable yet least prevented cancer due to low uptake of screening. Recognizing that many rural, low-income, and racial/ethnically diverse communities have disproportionately low screening rates, the National Colorectal Cancer Roundtable announced a campaign to achieve screening rates of 80 percent and higher in every community. Wisconsin has a screening rate of 73.4 percent; however, there is wide geographic variation among rural and urban clinics. The research team successfully developed a novel rural-urban geodisparity model that revealed significant disparities in CRC screening rates between rural and urban clinics. High-performing clinics, particularly those serving subpopulations with historically low screening rates, utilized stool-based screening tests more frequently, likely due to fewer resources and less access to colonoscopy facilities in rural areas. Additionally, the research team conducted interviews with clinic staff who highlighted the critical roles of medical assistants and primary care providers, shared decision-making and the need for stratified screening rate information to inform interventions aimed at reducing disparities and improving CRC screening practices.

In Wisconsin, one in three older adults is admitted to an intensive care unit (ICU) at or near the end of their life despite the vast majority expressing preferences to avoid such care. Patients in the ICU are often too sick to speak for themselves, and family members are asked to make these difficult decisions on the patient’s behalf. As a result of these challenges, surviving family members experience psychological distress after the patients’ ICU stay and ICU clinicians experience moral distress and burnout. Previous efforts to improve end-of-life ICU care have utilized time-limited trials which are agreements among patients, their surrogate decision makers, and clinicians to attempt life-sustaining treatment for a predefined period before evaluating whether the treatment is helping the patient. The specific objective of this project is to optimize the time-limited trial model to meet the needs of older adults admitted to the ICU and their surrogate decision makers. Successful completion of this project will determine whether the time-limited trial model of care leads to better end-of-life outcomes for patients, families, and clinicians.

Estrogen receptor positive (ER+) breast cancer is the most prevalent subtype of breast cancer in Wisconsin. Importantly, more than 25 percent of ER+ cancers recur at distant sites, or metastasize, even 20 years after initial diagnosis. This makes ER+ breast cancer the primary cause of breast cancer-related deaths in Wisconsin women. The primary goal of this project was to investigate how factors of the tumor microenvironment, such as collagen stiffness and fiber alignment, regulate the spread of cancer cells and promote dormancy. By better understanding ER+ breast cancer recurrence, this project has the potential to improve breast cancer treatment and help reduce future recurrences for patients with ER+ breast cancer.

The incidence of obesity has rapidly increased in Wisconsin and across the United States, and more than 65 percent of adults are overweight. Obese individuals are at increased risk for severe diseases including obesity-induced type 2 diabetes, cardiovascular disease, stroke and cancer. Previous research has shown that low levels of ALAS1, an enzyme involved in making the iron-carrying molecule heme for hemoglobin (a process known as heme biosynthesis), correlates with high body mass index and higher risk of developing type 2 diabetes. For this project, researchers hypothesized that ALAS1 may function as a metabolic sink to control the breakdown of amino acids in brown fat tissue. This project gave researchers a better understanding of the role ALAS1 plays in energy expenditure as it relates to obesity.