Results Realized

Since its founding in 1998, Women’s Health Research at Yale has funded investigators seeking to improve the health of women and understand the influence of sex and gender on health. Through our Pilot Project Program, our studies have generated results that are actively changing the healthcare landscape and the quality of care available to women.

Here are a few WHRY grant recipients whom we are proud to count among our growing number of talented and innovative collaborators achieving lasting results.

Early reports at the start of the coronavirus pandemic indicated that men were more likely to experience severe cases of COVID-19 and die from the illness. In response to these reports, WHRY funded Dr. Akiko Iwasaki to determine if the immune system of women and men reacted differently to the SARS-COV-2 virus.

Dr. Iwasaki identified clinically important sex differences in how the innate and adaptive immune systems differed in response to the virus. Her research uncovered that men had higher plasma levels of important innate immune cytokines that contribute to aberrant and excessive inflammation, while women were more likely to have robust T cell activation as an adaptive immune response than male patients during SARS-CoV-2 infection. Moreover, a poor T cell response negatively correlated with patients’ age and was associated with worse disease outcome in male patients, but not in female patients.

These fundamental differences in male vs. female immune responses during COVID-19 were subsequently confirmed in other studies. This study had a significant impact in the field of COVID-19 as well as in antiviral immunology, increasing the awareness of important sex differences in immune responses and the need to examine this issue in future studies.

As a professor of both therapeutic radiology and genetics, Dr. Peter Glazer investigates new therapeutic strategies for treating cancer and the role of altered DNA repair in tumor progression.

Based on a discovery from his laboratory showing that a lupus antibody can penetrate cancer cells and sensitize them to radiation and chemotherapy, Dr. Glazer initiated a WHRY-funded study to uncover the biological basis for how this occurs – the next step in moving toward a treatment intervention. Now, having identified the biological underpinnings of this finding, the potential exists to treat cancers that develop from inherited mutations to the tumor suppressing BRCA2 gene, such as ovarian and breast cancer. His novel process to use this antibody as a cancer therapy is being investigated in clinical trials.

Elected to the National Academy of Medicine for his accomplishments. Dr. Glazer also received an Outstanding Investigator Award from the National Cancer Institute to support his efforts in developing novel DNA repair inhibitors for cancer therapy.

Dr. Caroline Johnson is an expert in metabolomics - the scientific investigation of the byproducts or metabolites, such as sugars or amino acids, that are formed during metabolism. This biological process provides the energy for cells to function and can also fuel the growth of cancer cells. Metabolites act as chemical fingerprints that provide critical clues to the biological pathways contributing to colon cancer tumor growth and are the targets for potential therapies. Dr. Johnson’s interest was to examine the patterns and pathways of metabolites to help explain why women are at greater risk than men for more aggressive right-sided colon cancer, which has a higher mortality rate than the more common left-sided colon cancer.

With WHRY Pilot Project funding, Dr. Johnson explored the novel hypothesis that the metabolic process that produces the energy needed for this more aggressive tumor growth is different in women and men. The results of her research showed that colon cancer tumor cells in men use a type of metabolism known as anaerobic glycolysis, which provides short bursts of energy limiting how much a tumor can grow. However, tumor cells in women produce energy by breaking down fatty acids, which provides more sustained energy, thus feeding the more aggressive form of colon cancer.

Moreover, she pointed to how food, bacteria in the colon, and hormones can affect the metabolite produced, which may help explain why post-menopausal women who are producing lower levels of estradiol are at higher risk for colon cancer. This understanding is also critical to identify opportunities for intervention, including lifestyle changes, that could slow or prevent disease.

Her work using metabolomics to investigate the relationship of metabolism and the growth of colon cancer cells resulted in a Research Scholar Grant from the American Cancer Society.

As an active clinician, Dr. Pamela Ventola saw the value of a social-behavioral treatment intervention for autism spectrum disorder (AUD) called Pivotal Response Therapy (PRT). However, PRT had been developed and tested with boys, and not on girls with AUD.

In a WHRY-funded study, Dr. Ventola showed, for the first time, that PRT helped girls as well as boys, and that the net benefit was greater in girls than boys. These findings led to greater implementation of PRT in children with AUD.

Results also led to team-based research focused on identifying girls and boys who were most likely to respond to PRT, and this work was successful in identifying a brain signal that predicts a positive response to PRT before therapy begins.

Finding a pretreatment predictor of a good response is key because this is an intensive sixteen-week intervention requiring direct clinician intervention plus parental guidance. Moreover, early childhood is a window of opportunity for effective treatment that reduces the long-term personal cost for child and family.

Dr. Bruce Haffty is a radiation oncologist and breast-cancer researcher whose work changed how women and their doctors approach the assessment of risk for recurrent breast cancer.

With a WHRY grant, Dr. Haffty showed that patients with mutations in the BRCA1 and BRCA2 genes, even after they had already been diagnosed and undergone treatment for breast cancer, remained at greater risk for breast cancer than women without these mutations. His long term, 15-year follow-up of patients after a breast cancer diagnosis found these mutations continued to predispose women to new tumors and showed higher rates of occurrence in both the previously treated breast and the untreated breast.

This landmark discovery, which was published in The Lancet, provided information that women and their physicians needed to make more informed health decisions regarding both current treatment and cancer prevention. Furthermore, Dr. Haffty’s ongoing cancer research has paved the way for new methods of radiation therapy that use molecular and genetic data to determine treatments that reduce radiation resistance and improve outcome in breast cancer patients.

Dr. Peter Salovey, as a WHRY-funded investigator, examined the types of public service health messages that were effective in encouraging women at elevated risk for breast cancer to use routine mammography screening.

In this study, Dr. Salovey found that for health messages to be effective they must be tailored to an individual’s information-processing style. While there is a level of efficacy in health messages framed around both gains and losses if action is or is not taken, Dr. Salovey found that to harness the greatest power of persuasion, the context of the messages and their intended goal must be considered. For example, a woman may be more likely to respond to hearing the positive benefits of screening rather than the negative outcomes she may endure without it.

Dr. Salovey found that employing social psychology in patient-specific messaging resulted in increased rates of health protective behaviors. This work went on to maximize the power of messaging to persuade people to change risk behavior related to sun exposure, tobacco use, and HIV/AIDS.