Focus Area: Research

Obesity and type 2 diabetes (T2D) are major public health challenges, with impaired branched-chain amino acid (BCAA) metabolism playing a key role. Restricting dietary BCAAs or using the FDA-approved drug 4-PBA improves body composition, glucose control and lifespan in animal models. Exercise is also critical for weigh loss and maintaining muscle mass, but its interaction with BCAA-targeted interventions is unknown. This project will test whether dietary BCAA restriction, 4-PBA, and exercise—alone or in combination—reverse obesity and improve metabolic health in mice. Using genetic knockout models, it will also determine whether these benefits depend on the mitochondrial BCAA carrier Slc25a44. Findings will provide insights into diet- and drug-based strategies that can be paired with exercise to combat obesity and T2D. By focusing on accessible interventions, the study has the potential to promote health equity in communities disproportionately affected by metabolic disease.

Heart failure after myocardial infarction (MI) remains a leading cause of death because scar tissue formation prevents the heart from restoring lost function. Stem cell therapies hold promise, but human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have raised safety concerns due to arrhythmias. Early evidence suggests that cardiac progenitor cells (CCPs) may be safe, more versatile and better suited for cardiac repair. This project will use advanced cardiac slice models and dual optical mapping of voltage and calcium signals to study how CCPs integrate electrically and functionally within heart tissue. By clarifying the mechanisms of CCP behavior and viability, the study aims to advance the development of safe, more effect regenerative therapies for patients with heart failure.

Recurrent respiratory papillomatosis (RRP) is a lifelong disease caused by low-risk HPV types 6 and 11 that produces fast-growing lesions on the vocal folds, leading to hoarseness, repeated surgeries, scarring and significant community and quality-of-life challenges. There is no cure. This project uses a novel immunocompetent mouse model to investigate how vocal fold injury enables papillomavirus to evade immune defenses, establish chronic infection and drive disease recurrence. This study will define the threshold of viral load and injury needed for disease, test whether injury promotes recurrence and explore how injury disrupts epithelial and immune balance. Findings will advance understanding of how RRP develops and persists, informing future strategies for prevention and treatment.

Alzheimer’s disease (AD) affects more than 110,000 older adults in Wisconsin and remains without a cure. Emerging evidence suggests the gut microbiome may play a role in AD pathology, but how these changes unfold over time is not well understood. This project will analyze longitudinal fecal samples, fluid biomarkers and cognitive scores from participants in the Wisconsin Registry for Alzheimer’s Prevention (WRAP) and the Alzheimer’s Disease Research Center (ADRC). The study will test whether shifts in gut microbiome composition are linked to amyloid status, cognitive decline and AD biomarkers in plasma and cerebrospinal fluid. Findings are expected to identify specific gut microbes associated with AD progression, laying the groundwork for future therapeutic targets and larger multicenter studies.

Patellar tendon injuries are common and can lead to lasting mobility issues. Exercise is the best treatment, but current methods often misjudge actual tendon load, limiting recovery. This project uses new UW—Madison – Shear Wave Tensiometry (SWT) to directly measure tendon load and quantitative ultrasound (qUS) to assess tendon health. It will test how neuromuscular electrical stimulation (NMES) enhances tendon loading and explore links between tendon structure and function. The findings will guide more precise rehabilitation strategies, improving healing and long-term outcomes for people with tendon injuries.

Cardiovascular disease remains the leading cause of death in the U.S., in part because the adult heart cannot regenerate after myocardial infarction (MI). This project explores how inhibiting succinate dehydrogenase (SDH) in myofibroblasts can reduce fibrosis and promote heart repair. Preliminary studies show SDH inhibition reprograms fibroblast metabolism, limits scar formation and boosts cardiomyocyte regeneration. By uncovering the mechanisms behind this process, the study aims to pave the way for new regenerative therapies to improve outcomes after heart attack.

Primary hyperparathyroidism (PHPT) affects 3 million Americans and increases risks of fractures, kidney stones and cardiovascular disease. Surgery is the only cure, yet fewer than 10% of patients receive it. In Wisconsin, patients in highly disadvantaged neighborhoods are treated at half the rate of others. This project will use patient interviews to understand barriers to diagnosis and treatment, then develop educational tools for both patients and providers to improve referrals and access to surgery. The study aims to reduce disparities in PHPT care and improve outcomes for underserved communities.

The Role of the EnvCT in SIVmac Viral Fitness project is exploring a hidden part of the HIV virus that could open new doors for vaccine development. While most efforts focus on the virus’s outer surface, this research studies the envelope’s cytoplasmic tail (EnvCT) to see how it influences immune recognition and viral survival. By testing antibody responses and mapping how EnvCT interacts with host cells, the project aims to uncover new strategies to make HIV more vulnerable to prevention and treatment.

This project aimed to improve the care of Wisconsin residents living with dementia by increasing primary care provider and trainees’ knowledge and skills related to dementia diagnosis and management of the behavioral and psychological symptoms of dementia (BPSD). Alzheimer’s disease currently affects 110,000 Wisconsinites and the number is expected to increase to 130,000 by 2025. About 90 percent of individuals with dementia experience BPSD, which includes depression, physical aggression, wandering and sleep disturbance, among others. As a result, there is a need to train future and practicing primary care clinicians in the identification and management of BPSD to help caregivers manage these behaviors in the home setting, potentially preventing crisis escalation and unnecessary institutionalization. The project successfully increased medical trainees’ and primary care providers’ knowledge and skills in dementia diagnosis and BPSD management. A web-based curriculum for third- and fourth-year medical students at the University of Wisconsin School of Medicine and Public Health improved students’ self-reported attitudes towards dementia care and informed the design of a new Dementia and Public Health elective that began in 2023. Additionally, academic detailing sessions for primary care providers at Richland Center Hospital and Milwaukee Health Services resulted in significant knowledge gains and improved confidence in managing BPSD. Lastly, the DICE Approach was used to train social workers, nurses, medical assistants and assisted living and nursing home frontline staff and led to increased knowledge, self-efficacy and comfort in managing BPSD.

This research will study brain and cardiovascular health in transgender adult patients receiving gender-affirming hormone therapy at two timepoints: before hormone therapy begins, and after four to six months of therapy. The goal of the study is to assess links between gender affirming hormone therapy, cardiovascular health and brain structure and function. MRI will be used to analyze brain structure and brain blood flow. Body fat will be assessed by Dual X-ray Absorptiometry and aerobic fitness will be assessed using a treadmill test. This analysis is also relevant to other conditions involving hormone disruptions such as puberty, menopause, pregnancy, aging, postpartum, diabetes and obesity. Collaborators: Veena Nair, PhD, scientist, Department of Radiology; Oliver Wieben, PhD, professor, Departments of Medical Physics and Radiology; Kevin Johnson, PhD, associate professor, Departments of Medical Physics and Radiology; Jen Rehm, MD, associate professor, Department of Pediatrics; Dawn Davis, MD, PhD, professor, Department of Medicine