Grant Type: Faculty Grant

Carey Gleason, PhD, associate professor, Department of Medicine, and co-principal investigators Maria Mora Pinzon, MD, MS, assistant scientist, Department of Medicine, and Melissa Metoxen, senior student services coordinator at the Native American Center for Health Professions were awarded a COVID-19 Response grant for utilizing social media and community advocates to address health consequences of COVID-19 in Black, Latinx and American Indian communities. The overarching goal of this project is to continue disseminating accurate information created by community advocates through social media about COVID-19 and evaluate the effectiveness of social media messages on changing beliefs, attitudes, and adoption of behaviors related to COVID-19 and vaccination.

This project, Defining and Targeting Novel Anti-viral and Anti-cancer T cell Immunity, investigated the role of nuclear-to-cytoplasmic (N→C NF-κB) signaling in regulating CD8+ T cell responses to infections and cancer. The researchers aimed to understand how N→C NF-κB signaling affects CD8+ cell regulation during viral infections and tumor responses. They found that inhibiting the N→C NF-κB pathway led to improved anti-tumor responses in their mouse model, NEMODK. However, in chronic viral infections, the model had reduced virus control, suggesting its importance in CD8+ T cell differentiation. The research team explored a drug that targeted the NF-κB pathway and showed promising results in tumor regression. The study has received NIH funding to further investigate the mechanisms of a NF-κB inhibitory drug.

Humans rely heavily on vision, primarily facilitated by cone photoreceptors in the macula, which provide high-definition spatial and chromatic resolution. Macular degeneration, a leading cause of blindness, affects about 20 percent of people over 45 in Wisconsin. Recent advances in human pluripotent stem cell (hPSC) engineering have made it possible to create 3D retinal organoids (ROs) that mimic the retina’s structure but have yet to demonstrate the phototransduction needed for vision. The goal of this project was to demonstrate that cone cells in lab-grown ROs can respond to light like those in a healthy human eye and test gene therapies to restore vision in patients with achromatopsia. The researchers found that cells in lab-grown ROs had slower and less sensitive responses compared to those in mature primate eyes and confirmed the immaturity of the ROs through 3D mapping of cell connections. The lack of a retinal pigment epithelial (RPE) layer, essential for recycling vision pigments, resulted in limited light sensitivity, but adding artificial pigments improved the cells’ response to light. Using stem cells from achromatopsia patients, the team created ROs that mimicked the condition and they are now testing nanoinjection for delivery of gene therapy after unsuccessful attempts with viral vectors. Overall, this project has made significant strides in understanding and improving lab-grown retinal cells’ function.

This project, led by Dr. Ivan Rosado Mendez, aimed to develop and implement ultrasound microvessel imaging (UMI) as a functional imaging technique to study cervical remodeling during pregnancy in real time. Cervical remodeling describes the progressive changes of the cervix during pregnancy and involves four phases: softening, ripening, dilation and postpartum repair. If the cervix ripens in preparation for delivery too early, it can cause premature birth. Preterm birth (PTB), defined as delivery before 37 weeks of pregnancy, results in one million deaths worldwide and is associated with significant racial and socioeconomic disparities. The researchers successfully developed a cervical tissue-mimicking model, called a phantom, composed of agar-based simulated tissue, fluid-carrying channels, blood-mimicking fluid and a system to control fluid dynamics. They validated channel dimensions with micro-CT scans, ensured stability over 14 days and selected a fluid that best matched the features of human blood for the prototype. Finally, the team implemented a high-resolution imaging protocol that was able to detect fluid movement through the channels even when surrounded by simulated tissue.

Using the COVID EHR Cohort at the University of Wisconsin (CEC-UW), this project aimed to analyze the disproportionate impact of COVID-19 on racial and ethnic minority groups in Wisconsin, compare disease outcomes between UW Health and other health systems and test associations between risk factors, treatments and vaccine status with disease outcomes. CEC-UW has been collecting electronic health record (EHR) data from all COVID-19 patients across 21 participating health systems and, as of September 2021, has compiled more than 250 EHR elements from 1.1 million COVID-19 patients. This data has the potential to help target high-risk individuals, improve treatment, guide variant management and enhance response to future disease outbreaks. The results revealed that Black and Hispanic communities, along with low-income groups, faced significantly higher infection rates and more severe COVID-19 outcomes. Comparison of outcomes between health systems showed that UW Health patients had better recovery rates and lower mortality due to more effective health strategies, including advanced treatment protocols and higher vaccination rates. Finally, the project found that early treatments and full vaccination greatly improved outcomes, while those with underlying conditions or lack of vaccine access faced worse outcomes.

Filiz Yesilkoy, PhD, assistant professor, UW–Madison College of Engineering, Department of Biomedical Engineering, and co-principal investigators Irene Ong, PhD, assistant professor, Department of Obstetrics and Gynecology and Miriam Shelef, MD, PhD, associate professor, Department of Medicine, developed a user-friendly, cost-effective, point-of-care serology test for monitoring protective immunity against COVID-19. By developing this biosensor platform, investigators can more easily assess vaccination status, past infection status and protective immunity to inform communities in Wisconsin of the risk of COVID-19.

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.

The Vascular Effects of the Precision Interventions for Severe Asthma (VASC-PreCISE) led by Matthew Tattersall, DO, MS, associate professor, Department of Medicine, aimed to investigate biomarker-guided treatments for asthma and their impact on arterial injury and cardiovascular risk, focusing on improving blood vessel function and reducing inflammation through novel therapies. Asthma affects over 500,000 individuals in Wisconsin, with higher hospitalization and mortality rates among ethnic minorities. Certain asthma types, particularly persistent or late-onset forms, are linked to increased cardiovascular disease (CVD) risk due to shared inflammatory pathways. This connection represents a knowledge gap and a need for targeted approaches in treating both asthma and CVD. The VASC-PreCISE successfully enrolled 25 participants and collected 75 blood serum samples along with 75 ultrasound scans of participants’ carotid and brachial arteries to evaluate blood vessel health and inflammation. Data analysis was scheduled for February 2024 post-randomization to maintain trial integrity. Ultimately, this project fostered partnerships and led to a KL2 Scholar Award to continue research on precision asthma anti-inflammatory therapies.

Emerging and recurring viral infections remain a threat to public health and personal well-being. This innovative project proposes to “rediscover” rheumatoid factor (RF), a naturally occurring autoimmune antibody generally considered a hallmark of rheumatoid arthritis, as a unique, universal antiviral agent. The primary goal of this proposal is to learn more about the role of RFs in COVID-19 in order to inform the development of a universal antiviral treatment for rapid deployment during seasonal, endemic and future viral pandemics. The findings have the potential to inform the development of novel therapeutics for treating wide range of viral infections.

This research team will investigate a novel potential mechanism underlying interstitial lung disease (ILD), a collection of diseases that produce progressive scarring, or fibrosis, of the lung. ILD, which remains largely untreatable and poorly understood, impacts more than 250,000 patients in the United States and causes a staggering 40,000 deaths each year. Since the onset of the COVID-19 pandemic, incidence of ILD has risen sharply. Nearly all patients intubated for COVID-19 have evidence of ILD. This study focuses on understanding how epithelial injury remodels its extracellular matrix microenvironment through the hexosamine biosynthetic pathway. The findings have the potential to advance the mechanistic understanding of how lung injury triggers scarring and identify therapeutic targets for stabilizing this progressive and intractable disease.