Grant Program: New Investigator Program

This project will evaluate precision methods for measuring key indicators of success for a targeted cancer immunotherapy to expand treatment options for patients with acute myeloid leukemia (AML), which typically has low treatment response rates and poses a challenge for inducing remission after relapse. The results of this project will support efforts to improve other targeted immunotherapeutic strategies for AML through broader application of the study methods.

Dr. Alexander Birbrair, assistant professor in the Department of Dermatology, is leading a crucial research project aimed at advancing treatments for melanoma. Melanoma is the fifth most common cancer in the United States, and it has disproportionately higher mortality rates in racial and ethnic minority populations. Cancer and the nervous system bear a close relationship, and the team is particularly interested in understanding how signaling from a receptor, called PAC1, impacts melanoma progression. The results of this project could inform clinical testing for medications targeting the PAC1 signaling pathway to treat melanoma, ultimately improving survival rates for all melanoma patients.

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.

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.

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.