Grant Program: New Investigator Program

Preterm birth affects 15 million babies worldwide every year, including ten percent of babies born in Wisconsin. Spontaneous preterm birth can occur when the cervix softens too early into the pregnancy to prepare for birth, and the risk of spontaneous preterm birth can be potentially characterized by changes in cervical vascularity due to increased inflammation. A project led by Ivan Rosado Mendez, PhD, assistant professor, Department of Medical Physics, will investigate the use of ultrasound microvessel imaging (UM) and ultrasound backscatter spectroscopy (UBS) in the study of cervical microvascular remodeling during pregnancy. Although ultimately the goal is to implement UMI in vivo, this project will first design, fabricate, and characterize a tissue-mimicking model to validate the use of UMI and UBS, as well as test the feasibility of the simultaneous use of UMI/UBS by assessing the accuracy of the images. If successful, this technology will contribute to clinicians’ knowledge with in-depth and objective information about important mechanisms surrounding preterm and at-term birth and inform future approaches and interventions for preventing preterm birth.

Death of photoreceptors in the retina is the ultimate cause of blindness in various diseases, including macular degeneration, and there are no treatment options available for this or similar retinal degenerative diseases. A new project led by Raunak Sinha, PhD, assistant professor, Department of Neuroscience and collaborator David Gamm, MD, PhD, professor, Department of Ophthalmology will launch novel research into retinal organoids, derived from human stem cells, as a potential replacement for damaged photoreceptors. This team’s findings have the potential to inform effective cures for blindness, and improve the vision, quality of life and independence of those suffering from macular degeneration and other blinding disorders.

Acute kidney injury is a common occurrence in premature infants in the neonatal intensive care unit and has significant implications for neonatal and long-term health outcomes, including permanent kidney damage. However, the current methods to detect kidney injury are inadequate. Matthew Harer, MD, Department of Pediatrics and collaborator Joshua Coon, PhD of the College of Agricultural Life Sciences, Department of Chemistry, will use their New Investigator Program award to evaluate a new method of detecting kidney injury, with the goal of identifying kidney injury before permanent damage. With early detection of kidney injury, the researchers will be positioned to design and test treatments that will result in healthier kidneys and lead to decreased chronic kidney disease as these babies become children and adults.

The prevalence of asthma, a chronic inflammatory condition, is higher in Wisconsin than the national average, and can lead to an increased risk of cardiovascular disease. Asthma also disproportionately afflicts children and ethnic minorities. Matthew Tattersall, DO, MS, Department of Medicine will lead the project Vascular Effects of Precision Interventions for Severe Asthma (VASC-PreCISE), which aims to find the ideal precision asthma therapy to address inflammation in asthmatics, and ultimately to reduce their risk for cardiovascular disease. Project collaborators include James Stein, MD, and Loren Denlinger, MD, PhD, of the Department of Medicine. Finding the correct, precision, novel therapy to address each asthmatics’ unique inflammation pattern has the potential to reduce patients’ cardiovascular risk. Moreover, addressing chronic inflammation at an early age may completely alter the cardiovascular risk of generations of asthmatic individuals.

The goal of this project was to increase compliance in postpartum care among Black women by incorporating community partnerships into the “Staying Healthy After Childbirth” (STAC) care model, which is a telehealth hypertension management program offered by UnityPoint Health-Meriter. Hypertension disorders affect around 22 percent of pregnancies in Wisconsin, with preeclampsia and eclampsia being 60 percent more common and substantially more severe in Black women than white women. While the American Congress of Obstetricians and Gynecologists recommends early outpatient follow-up for postpartum women with hypertension disorders, up to 40 percent do not attend. Initial data from the STAC program showed that it was successful in obtaining blood pressure readings from 94 percent of women, compared to 60 percent in standard follow-up, however, compliance with remote blood pressure monitoring varied 23 percent between Black and white women. The project successfully enrolled 48 out of 55 planned participants and integrated community-based, racially concordant doulas into their postpartum care. Preliminary findings revealed a significant improvement in health care engagement for Black mothers with doula support, as evidenced by their total blood pressure readings during the 42-day postpartum period. Qualitative feedback from study participants emphasized the program’s live-saving impact, particularly in postpartum recovery and medication management, with emotional support from doulas contributing to positive well-being and overall experience.

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, seeks to address these limitations by improving the nuclear targeting of gene therapy vectors. The team will use 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 studies and collaborations 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, will work 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 will create 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.

Led by Jasmine Zapata, MD, MPH, Department of Pediatrics, in partnership with the Today Not Tomorrow Family Resource Center and its collaborative partners: Project Babies (project of Today Not Tomorrow, Inc.), Harambee Village Doulas, and the African American Breastfeeding Alliance of Dane County, Inc., this project will implement the Today Not Tomorrow Pregnancy and Infant Support Program (TNT-PISP).

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.