Grant Program: New Investigator Program

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.

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.

Birth Cost Recovery (BCR) holds unmarried, non-custodial fathers liable for Medicaid birth costs in Wisconsin, yet there is little known about the impact of this policy on Black birthing people in Wisconsin. This project, led by Tiffany Green, PhD, assistant professor in the departments of Population Health Sciences and Obstetrics and Gynecology, worked to better understand how BCR and other similar social policies impact inequities in health outcomes among low-income Black birthing people in the state of Wisconsin. Dr. Green and a team of interdisciplinary experts in the fields of economics, population health, pediatrics, social work, clinical/social psychology and community engagement created an evaluation framework for BCR as a way of measuring the impact of this policy and collect evidence that can be useful in informing future policies and improving health outcomes statewide.

This project, led by Dr. Jasmine Zapata, aimed to evaluate the feasibility and preliminary outcomes of the Today Not Tomorrow Pregnancy and Infant-Support Program (TNT-PISP). TNT-PISP is a collaborative community-based prenatal care and support group in Dane County that was uniquely designed to serve Black women and infants. Wisconsin’s Black infant mortality rate is the highest in the nation and there is increasing evidence that models of prenatal care that are community-driven, group-based, culturally-relevant and family-centered have the potential to significantly improve maternal and infant health outcomes. The TNT-PISP generated significant short-, medium- and long-term impacts. The program provided valuable peer support and resources for Black mothers, with 98 percent of participants sharing that they would be willing to return. Thematic analyses highlighted positive effects of the program, including providing peer support, a safe space for Black mothers to share their experiences and valuable information about resources for parents, breastfeeding and community-based doula programs.

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.

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.

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.