Pilot Grants
The Women's Health Research Center funds multidisciplinary projects and studies across Mayo Clinic to advance research focused on the female body through all stages of life. Projects focus on illnesses, conditions and physiological responses that occur more often or only in women or manifest differently in women than in men.
2025 pilot grant awardees
Digital Biomarkers and Epigenetic Aging Among Women With Peripartum Cardiomyopathy
Demilade A. Adedinsewo, M.B., Ch.B.
Dr. Adedinsewo's research team is investigating the use of artificial intelligence (AI) to identify novel digital biomarkers for cardiovascular risk and clinical outcomes among women with peripartum cardiomyopathy. Peripartum cardiomyopathy is a rare but serious heart condition that occurs during pregnancy or after giving birth and is associated with high morbidity and mortality. The team uses an electrocardiogram-based deep learning algorithm — an approach referred to as AI-ECG — to calculate biological age. Dr. Adedinsewo and colleagues are particularly interested in how AI-ECG-derived biological age correlates with epigenetic markers in people with peripartum cardiomyopathy. The team's goal is to determine whether these digital and molecular biomarkers can help predict disease progression and recovery.
The project builds on the team's strong foundation of prior work, including retrospective and prospective studies and a recent randomized controlled trial involving over 1,200 participants. These studies demonstrated that AI-ECG tools can reliably detect left ventricular systolic dysfunction, the clinical hallmark of peripartum cardiomyopathy. Notably, the AI-ECG algorithm has received clearance from the U.S. Food and Drug Administration, underscoring its clinical relevance. Preliminary analyses from the trial also revealed that AI-predicted biological age was strongly associated with increased risk of both left ventricular systolic dysfunction and all-cause mortality, suggesting its potential as a biomarker and prognostic tool.
With this pilot grant, the team is examining the relationship between AI-ECG-derived biological age and epigenetic markers in women with and without peripartum cardiomyopathy. Dr. Adedinsewo and her team are recruiting participants from the previous trial and expanding enrollment through established clinical networks. The overarching hypothesis is that AI-ECG biomarkers reflect underlying biological aging processes and can serve as early indicators of cardiovascular risk in obstetric patients.
Sex Differences in Exposure to Chronic Placental Inflammation and Its Impact on Infant Outcomes
Elizabeth Ann L. Enninga, Ph.D.
Chronic placental inflammation during pregnancy has a clear negative impact on a developing fetus; however, the longer term impact of this inflammation on childhood development is unknown. Dr. Enninga's study aims to identify whether there are differences in early childhood outcomes in boys and girls who were exposed to chronic placental inflammation in utero. An additional goal is to discover how the placenta may mediate these risks during pregnancy in male and female fetuses. This understanding can advance the development of targeted strategies for preventing the harmful effects of chronic placental inflammation on childhood outcomes.
Understanding Mechanisms of Healthy and Dyssynergic Defecation
Adil Bharucha, M.B.B.S., M.D.
Dr. Bharucha and his team are studying the coordination between the abdominal wall and anorectal muscles during defecation in healthy individuals and in patients with dyssynergic defecation. This condition affects a substantial proportion of patients with medically refractory chronic constipation and is associated with internal hemorrhoids, anal fissures and constipation-predominant irritable bowel syndrome. Dyssynergic defecation is five times more common in women than in men in Olmsted County, Minnesota.
Current concepts attribute dyssynergic defecation primarily to impaired anal relaxation. In contrast, Dr. Bharucha's findings suggest that the condition results from abdominoanal dyscoordination. Healthy defecation begins with abdominal wall expansion, coordinated with anorectal descent and increased rectal and anal pressure, followed by anal relaxation and evacuation once rectal pressure overcomes anal pressure. In dyssynergic defecation, excessive straining is accompanied by abdominoanal dyscoordination and reduced evacuation.
With this pilot grant, the research team aims to validate a noninvasive, low-cost device to assess diaphragm function and abdominal wall contraction during defecation. The team hypothesizes that, compared with healthy individuals, patients with dyssynergic defecation have changes in abdominoanal coordination and rectal pressurization during defecation. If confirmed, this hypothesis will inform a trial to redesign biofeedback therapy for dyssynergic defecation.
Characterizing Sex-Specific Impact of Alzheimer's and Alpha-Synuclein Pathologies
Elijah Mak, Ph.D.
Dr. Mak's pilot project aims to understand how biological sex shapes the interaction between Alzheimer's disease pathology and alpha-synuclein pathology across the cognitive continuum — from cognitively unimpaired individuals and those with mild cognitive impairment to people with Alzheimer's disease or Lewy body dementia. It is now established that women are more vulnerable to Alzheimer's disease pathology, while men more commonly exhibit alpha-synuclein pathology, the hallmark of Lewy body dementia.
However, the combined influence of both pathologies — and how this influence may differ by sex — remains poorly understood, particularly in individuals with coexisting Alzheimer's disease and Lewy body dementia. With this pilot grant, Dr. Mak's research team aims to address three overarching questions. First, do women show greater Alzheimer's disease pathology than do men when alpha-synuclein also is present? Second, do these copathologies produce different patterns of brain changes — structural, microstructural and metabolic — in women compared with men? And third, do sex differences in pathology and neuroimaging lead to faster clinical decline in women?
To address these questions, the research team is using brain imaging data from two well-characterized longitudinal cohorts: the Alzheimer's Disease Neuroimaging Initiative and Mayo Clinic's Lewy body dementia cohort. Participants in these cohorts have undergone a variety of brain scans, including MRI to look at brain structure, diffusion imaging to assess microstructural injury, and PET scans to measure AD pathology and brain metabolism. The team also uses a new laboratory test called seed amplification assay to detect the presence of alpha-synuclein.
By identifying sex-specific patterns in brain changes and clinical outcomes, this research aims to contribute to a deeper understanding of how biological factors such as estrogen and other hormonal influences affect women's brain health as they age. These insights could support future studies focused on tailoring prevention and treatment strategies specifically for women, advancing the broader goals of advancing sex-based and personalized medicine.
Harnessing Respiratory Muscle Training To Optimize Glycemic Control and Cardiovascular Outcomes in Gestational Diabetes Mellitus
Dongwook Yeo, Ph.D.
Gestational diabetes mellitus is a condition in which blood glucose levels become elevated during pregnancy. The condition is usually detected between 24 and 28 weeks. It affects approximately 7% to 14% of pregnancies worldwide. Gestational diabetes mellitus not only poses immediate risks to mothers and babies but also increases the risk of developing type 2 diabetes and high blood pressure later in life.
Currently, managing gestational diabetes mellitus mainly centers on healthy diet and regular exercise. Sometimes, medicines such as insulin or metformin also are used. However, sticking to a strict diet can be difficult during pregnancy due to hormonal changes, nausea and stress cravings for sugary foods. Medicines are typically used only when absolutely needed because of safety concerns. Exercise remains the safest and most cost-effective option, but as pregnancy progresses, growing belly size, discomfort and fatigue often make traditional workout schedules harder to maintain.
Dr. Yeo's team is exploring an alternative: respiratory muscle training. This approach involves controlled, resisted breathing exercises that build on Lamaze-style breathing already familiar to many women during labor. By adding gentle resistance, respiratory muscle training safely boosts energy use and can be easily combined with Lamaze, making it straightforward to apply in routine clinical care for women who struggle with traditional exercise later in pregnancy. It can help strengthen the breathing muscles, lower stress hormones such as cortisol and support healthy blood pressure. The team's recent studies show that respiratory muscle training can help manage blood sugar after meals. The training also may reduce extra pressure on the heart and lungs caused by the expanding uterus pressing on the diaphragm.
In this project, Dr. Yeo's primary goal is to test how effective respiratory muscle training is in lowering postprandial blood glucose levels in women with gestational diabetes mellitus. The team hypothesizes that a single session of respiratory muscle training can safely raise metabolic rate and increase the work of breathing, which in turn may help lower blood glucose and blood pressure in this population.