Grant Program: New Investigator Program

This project aims to transform ovarian cancer care by repurposing tumor cell-containing abdominal fluid (ascites) samples from patients to identify markers of treatment resistance. The ability to easily assess risk of resistance in patients would potentially eliminate the use of ineffective therapy and serve as a signal for determining when second-line therapies should be explored.

This project will utilize advanced neuroimaging and molecular pathology methods to evaluate the impact of brain tumor progression on patient neurocognitive function and quality of life while incorporating metrics that are innovative to neuro-oncology research. Through enhanced understanding of cancer progression on patient quality of life, this project aims to transform treatment and care for patients with brain tumors across Wisconsin and beyond.

This project is seeking to develop a novel diagnostic model for aspiration pneumonia (AP) through identification of a unique molecular signature for lung injury due to aspiration. Pneumonia is the leading infectious cause of mortality in older adults and about 15 percent of cases are due to AP, which currently lacks objective diagnostic criteria and methodology for identifying high risk patients. The results of this project could inform identification of effective interventions for AP and promote improved health outcomes for at-risk older adults throughout Wisconsin.

The inappropriate use of antibiotics in healthcare settings is a significant patient safety and public health threat. Older adults, particularly those living in long-term care facilities, often receive inappropriate antibiotic prescriptions in the emergency department and are at high risk for related complications. The primary issue leading to inappropriate antibiotic prescribing for older adults identified by this project was urine testing patterns that resulted in overdiagnosis of urinary tract infections. To address this, the researchers developed and implemented a new way for emergency care providers to order urine testing in the electronic health record which was associated with a significant decrease in unnecessary antibiotic use in older adults being evaluated for urinary tract infections.

Diabetes costs Wisconsin over $6 billion in health care costs each year. Diabetes is a particularly acute problem for minority groups in our state, affecting over 40 percent of American Indian and 20 percent of African American adults. Altogether, nearly two million Wisconsin residents are estimated to have diabetes or pre-diabetes, which are associated with diet and obesity. Because of this, dietary interventions that promote blood sugar control and a healthy weight are needed. The researchers found that reducing dietary levels of three amino acids restored blood sugar control and normal body composition in obese, insulin-resistant mice, even if they consumed a high-fat, high-sugar diet. Further research will test the translatability of the findings to humans.

In Wisconsin, 750,000 people live with diabetes, and 25 percent of those individuals will develop a diabetic foot ulcer (DFU), a common complication of diabetes, in their lifetime. DFUs can remain open for a long time, and it can be difficult to predict which of these wounds will respond to treatment and heal or require amputation. Wound tissue supports the colonization of a diverse community of microbes referred to as a microbiome. The microbiome in the wound tissue is thought to sustain inflammation which impairs healing and tissue repair. There is a critical, unmet need to develop methods that predict if diabetic wounds will heal in response to treatment, or if they will remain open and healing will be stalled due to a complex microbiome. In this study, researchers hypothesized that the wound microbiome interacts with host healing pathways and genes that control tissue repair. Ultimately, they found that anaerobic bacteria species, which can survive and grow with no oxygen, are more abundant and transcriptionally active in the microbiome of persistent and amputated wounds. Therefore, anaerobic bacteria may serve as a predictive biomarker of wound healing. The research team has received a $26,000 Wisconsin Alumni Research Foundation (WARF) Technology Accelerator Grant and a $2 million NIH grant to expand their work.

Lupus — an autoimmune disease that causes inflammation and organ damage — disproportionately affects patients of color and those of low socioeconomic status, who also experience higher rates of associated kidney disease and early death. Ensuring that patients get regular care could help keep symptoms in check, but retention predictors in lupus care are poorly understood. This study defined retention in care for different demographic groups in Wisconsin, finding that those from the most disadvantaged neighborhoods were the most at-risk of ~60% lower retention in care. The insights generated from this research have the potential to help providers reduce lupus outcome disparities in the future.

Studies have implicated the failure of proper chromosome segregation, a process that is critical for cell proliferation and for maintaining life in all organisms, in both cancer and birth defects. This project explored the scientific premise that the kinetochore, a protein structure that forms during cell division, ensures proper chromosome segregation and prevents errors in mitosis. This project provided fundamental insights into cancer and developmental diseases by yielding new understanding of kinetochore functions. Through the work completed during this grant period, the researchers were able to make progress on developing a novel super-resolution imaging methodology which is not only well-suited to studying kinetochore dysfunction, but also can be utilized for broad research fields.

Heart failure continues to be a major health issue in the United States, characterized by 6 million adults affected in the years 2015-2018, according to the American Heart Association. Ischemic injury is caused by the absence of or diminished flow of blood, which can lead to heart disease and heart failure that affects the function of the heart by reducing its ability to pump blood effectively. This project explored new strategies to repair the adult human heart following injury caused by heart disease, which can cause irreversible loss of part of the heart muscle. The research team identified mechanisms that occur in heart regeneration in newborns that could be applied to adult hearts in order to aid in cardiac regeneration. These data support the possibility of people regaining cardiac function after injury.

Diabetes affects almost 600,000 people in Wisconsin and costs state residents $6.15 billion per year, numbers which are expected to triple in the next 15 years. Type 2 diabetes (T2D) accounts for the majority of these cases and is linked to the failure of insulin secretion from pancreatic β-cells (beta cells) that keep blood sugar in check. These rapidly climbing number pose a significant burden on the healthcare system. The researchers identified a new potential target for diabetes therapy, the metabolic enzyme pyruvate kinase (PK), which has been found to be sufficient in initiating and amplifying insulin secretion. Their work suggests that PK activation could be utilized to promote the healthy metabolic function of β-cells in order to prevent or reduce T2D.