A female doctor examining a female patient.

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 only in women or manifest differently in women than in men.

2024 pilot grant awardees

Effect of estradiol in the immunopathology of MAC infection

Dr. Escalante and Dr. Pathakumari are studying how estrogen affects the immune response brought on by MAC infection. Accumulated evidence shows that sex can play an important role in susceptibility to infectious diseases, including MAC infection. MAC lung disease is the most common nontuberculous mycobacterial infection — especially in women who have gone through menopause — and remains challenging to treat. Scientists don't know how hormonal changes during menopause, including changes in estrogen, affect the immune response in the lungs of people who have MAC infections.

Dr. Escalante and Dr. Pathakumari hypothesize that women are more susceptible to MAC infection after menopause because hormonal changes affecting their lungs are associated with immune dysfunction, lack of inflammatory mediators or both.

Within the Mayo Clinic Thoracic Research Disease Unit, Dr. Escalante, Dr. Pathakumari and team are using newly designed mouse model and human blood samples to study the effect of estrogen on MAC infection-induced immune response in vitro. Specifically, they are assessing the effects of estradiol on inflammatory mediators and genes associated with immune response against MAC infection by studying mice with MAC infections as well as blood immune cells from patients with MAC infections and healthy volunteers in the presence and absence of estradiol. The team also compares the course of infection, inflammatory mediators and bacterial burden between male mice, female mice, and ovariectomy female mice in the presence and absence of estradiol.

The research team aims to determine the relationship between endogenous estrogen exposure and the risk of MAC lung disease in women who have completed menopause. The team also hopes to improve the understanding of the impact of estrogen on MAC lung disease onset and progression. If successful, the team's newly designed mouse model of MAC lung disease will be a valuable tool to identify new therapeutic targets that can be studied for prevention and treatment of MAC infection, which would be of great benefit for women at risk of this difficult-to-treat disease.

Individualized women's healthcare in fibromyalgia

The goal of this pilot project is to establish a research pipeline for the neurobiological assessment of women with fibromyalgia, using pain sensitivity testing, neuroimaging, and physiological measures of sleep and activity. Dr. Irani's research team is using traditional and AI-derived analyses to develop an individualized medicine approach for patients with fibromyalgia, who currently have few effective treatment options.

Fibromyalgia is a common condition that causes widespread chronic pain, fatigue, sleep and mood disturbances, brain fog, and a range of other symptoms affecting almost any part of the body. It is significantly more common in women than men and, although it can occur at any age, it most frequently occurs in people ages 50 to 60 years old. Patients with fibromyalgia have health care costs approximately three time those of the same age and sex without the condition. There also is a measurable impact on society, as around 25% of patients are unable to work within five years of developing symptoms.

The diagnostic criteria for fibromyalgia have been revised several times. But in the absence of clear physical signs, diagnostic tests or specific biomarkers, the population of patients with fibromyalgia remains extremely heterogenous and may include multiple subgroups of people with different clinical characteristics. For example, one subgroup of patients may report high levels of pain and physical impairment, but low levels of mood and cognitive disturbance compared with another subgroup characterized by high levels across all symptom domains. Addressing the multifactorial nature of pain is essential for developing a tailored management plan. Current guidelines acknowledge that a one-size-fits-all approach is likely to fail and highlight the need for a stratified medicine solution. Dr. Irani aims to develop an evidence-based method for achieving such a solution.

Some techniques can help evaluate underlying biological factors of fibromyalgia pain, which can help predict treatment response. Quantitative sensory testing gauges pain sensitivity. Brain imaging may reveal structural and functional changes in the brain. And physiological measures of sleep and activity also could help researchers better understand both the complex mechanisms underlying this condition as well as their impact on treatment response.

A randomized controlled trial to determine the efficacy of a multidisciplinary pain management program for treating aromatase inhibitor-associated musculoskeletal symptoms (AIMSS) in women who have had breast cancer

  • Barbara K. Bruce, Ph.D., L.P.

Aromatase inhibitors are highly successful in preventing relapse in patients with breast cancer. However, these medicines cause severe side effects in a significant percentage of patients, often leading to early discontinuation and the loss of potential life-saving benefits. The side effects, collectively referred to as AIMSS, include pain, joint stiffness, arthralgias, myalgias and tendinopathy. There is currently no treatment for AIMSS.

Dr. Bruce's research team is conducting a randomized controlled trial to determine the efficacy of a multidisciplinary pain management program for patients who have previously had breast cancer. This project compares the pain management intervention with the usual care for AIMSS in Mayo Clinic's Breast Clinic to determine the program's effectiveness in reducing AIMSS and improving adherence to aromatase inhibitor medicines.

To address this critical need, Dr. Bruce and colleagues developed an intervention program for AIMSS with the goal of decreasing these side effects to achieve continued adherence to these medications. The team has already tested the feasibility of administering this program to 70 patients with a history of breast cancer and a diagnosis of AIMSS. The program was well received by patients and their doctors, and the team used their feedback to refine the program. In this project, Dr. Bruce's team is building on its previous work with a randomized control trial to demonstrate the program's efficacy compared with treatment as usual.

Dr. Bruce hypothesizes that patients with AIMSS who are referred to the treatment program will have high levels of pain, psychological distress and functional impairment at baseline. She anticipates that patients who participate in the treatment program will show significant improvement in pain levels, psychological distress and functioning at 3-month, 6-month and one-year follow-ups when compared with usual care. Dr. Bruce has identified patients' psychological distress as the strongest predictor of baseline functioning and improvement after completing the program. Her goal is for patients who complete the program to show significant improvement in medication adherence at each assessment interval.

Determination of chorionic villi DNA methylation profile and intrauterine biomarkers in patients with first trimester pregnancies

Ruptured ectopic pregnancy is the leading cause of pregnancy-related maternal death in the first trimester. Earlier detection and more efficient triage in the workup of early pregnancies whose locations are unknown could reduce this danger. Dr. Larish's project is focused on finding a methylation profile of early placental DNA — also called chorionic villi — as well as biomarkers within the uterus that could detect and locate pregnancies during the first trimester.

Recently, scientists have studied the use of tampons as novel tools to diagnose diseases of the lining of the uterus and the cervix. It is possible that tampons also could serve as devices to locate pregnancies. Dr. Larish is collecting information on the signature of early placental DNA and testing whether this DNA is shed through the cervix and able to be collected on a tampon. Finally, she is investigating the possibility that a tampon-based DNA detection approach can locate intrauterine pregnancies earlier than ultrasound.

Dr. Larish's research team aims to be able to locate intrauterine pregnancies earlier for some patients and to find warning signs that could trigger earlier interventions for others. This would reduce imprecision in diagnosis of pregnancy of unknown location, reducing unnecessary interventions for nonviable intrauterine pregnancies and improving the triage of those at higher risk of ectopic pregnancy.

Sex-specific disparities in Black versus white people in the United States with multiple sclerosis (MS)

This project examines sex-specific disparities in Black Americans and white Americans with multiple sclerosis (MS). There are significant sex differences in MS. It is more common in women and more common for women to have relapses. In contrast, disabilities caused by the disease often get worse, faster in men. In addition, there also are significant racial differences in the way MS progresses in different people. In the United States, Black patients with MS usually have a more aggressive disease course than white patients.

Biological factors and social determinants of health are some of the underlying factors leading to these differences. Dr. Zeydan is investigating the interaction between sex and race in MS, and how this interaction may worsen disparities in MS. She is evaluating clinical and imaging metrics of Black versus white patients with MS in the United States to better understand these differences.

Harnessing spatial transcriptomics to understand the factors mediating pancreatic islet cell adaptation in human pregnancy

Dr. Egan and colleagues are investigating mechanisms that control glucose during and after pregnancy. Type 2 diabetes is a major risk factor for cardiovascular disease and is associated with a gradual decline in function of the endocrine pancreas. And pregnancy is a major stressor of pancreatic function. Gestational diabetes occurs when the pancreas is unable to adapt to the demands of pregnancy. It affects 14% of pregnancies and is associated with adverse pregnancy outcomes, including a doubling in cesarean delivery rates and a 30% increase in high-birthweight infants. Studies to prevent gestational diabetes have yielded disappointing results, and treatment options are limited.

Although more than 60% of women who experience gestational diabetes develop prediabetes or permanent type 2 diabetes within 10 years, there are few effective prevention strategies. And women who have multiple pregnancies may have permanent damage to pancreatic function, as parity is an independent risk factor for type 2 diabetes. Despite these adverse outcomes, the mechanisms controlling pancreatic changes during pregnancy are not clear.

Dr. Egan's research team is applying the novel technique of spatial transcriptomics to human pancreatic tissue from the Mayo Clinic autopsy database. The team aims to identify differentially expressed genes in specific endocrine pancreas cell types that are responsible for the regulation of glucose in pregnancy. This pilot study will lay the groundwork for future work targeting specific pathways aimed at preventing gestational and type 2 diabetes in women.