Women’s Health Research at Yale to fund four new studies

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Women’s Health Research at Yale (WHRY) today announced funding for studies to tackle ovarian cancer, heart attacks, obesity, and the effect of cannabis on the brain.

With seed money through this year’s Pilot Project Program — including two Naratil Pioneer Award recipients for research on the verge of a significant breakthrough — the researchers aim to answer questions vital to improving women’s health and uncovering sex and gender differences to benefit everyone.

These questions include: Do women’s brains make them more susceptible to cannabis addiction? How can healthcare providers better diagnose and treat women who show different signs of having a heart attack? Can a virus that has been shown to eliminate a type of brain tumor also be effective in treating ovarian cancer? And what can understanding the sex-specific formation of fat deposits in females reveal about their risk for obesity and developing diabetes, heart disease, and cancer?

“Women and men are different, and they have different health needs,” said Dr. Carolyn M. Mazure, director of WHRY. “These studies will advance our understanding of these differences, helping lead the way to more gender-specific approaches for the health conditions and habits that most affect women and men today.”


Cannabis use

Kelly Cosgrove, associate professor of psychiatry, radiology and biomedical imaging, and neuroscience, will receive the Wendy U. and Thomas C. Naratil Pioneer Award to examine how smoking cannabis affects the brain in women and men. As Cosgrove notes, there are differences in the ways males and females initiate use of cannabis, progress to dependence, and experience withdrawal symptoms. Her focus will be to determine the sex-specific mechanisms underlying the drug’s rewarding properties and the potential for addiction.

“Cannabis is generally thought of as a safe drug despite a substantial number of studies showing negative, potentially long‐term effects on the brain, including cognitive dysfunction and mental illness,” Cosgrove said. “Over the past 30 years, cannabis has become increasingly potent, with its major psychoactive ingredient content growing from an average of 1.5% before the 1980s to current strains that contain upwards of 25%.”

Over the last 20 years, 24 states and the District of Columbia passed laws making cannabis legal for medical or recreational use, even as it remains illegal under federal law. Moreover, cannabis is the most commonly used illicit drug in the United States, with about 22 million people reporting having used it in the previous month. While use of other drugs has declined in recent years, cannabis use has grown.

According to a 2014 national survey, 4.2 million Americans have a marijuana use disorder, defined as use that causes significant problems with health or the ability to meet responsibilities.

Cosgrove’s team has developed a way of using a type of brain scan to show sex differences in the neurochemical response to smoking a tobacco cigarette. They plan to adapt this method and scan men and women smoking cannabis, expecting to see a faster reward response in women at the brain’s suspected hub of drug reinforcement.

“Neurochemical sex differences have been documented for tobacco smoking and alcohol dependence, and we need to find out if there are sex differences in the neurochemistry of cannabis use in humans,” Cosgrove said. “We need to investigate these differences so people can understand what cannabis does to their brains and — for people who become addicted — allow for the development of gender-sensitive treatments.”


Obesity

More than one-third of adults in the country are considered obese. Combining obese adults (those excessively overweight for their height) with less severely overweight adults, 69% of the nation’s people are at an unhealthy weight.

While obesity can be found in about equal numbers of women and men, obese women suffer up to eight times greater rates of obesity-related conditions, such as heart disease, stroke, and type 2 diabetes. It’s not clear why.

Matthew Rodeheffer, associate professor of comparative medicine and molecular, cellular and developmental biology, will also receive a Wendy U. and Thomas C. Naratil Pioneer Award to determine if the molecular pathways driving the growth of fat cells are fundamentally different in females. If so, this would identify a key mechanism that links increased fat mass to metabolic disease in women.

Rodeheffer plans to continue research he first advanced with a 2011 WHRY grant that focused on how women’s body fat increases in obesity.

In that previous research, Rodeheffer’s team showed that obese female mice generate more under-the-skin fat cells while obese male mice do not, suggesting mice could be used to model sex differences in fat distribution. In addition, they showed that removing estrogen from female mice causes them to gain weight in a male pattern.

The new study aims to define how fat cell production is increased in female obesity and determine if the increase in under-the-skin fat cells affects the onset of obesity-associated diseases in females.

“We have learned that females develop fat in different patterns,” Rodeheffer said. “But there is still much to learn about the molecular mechanism driving this difference and how it relates to metabolic disease. We hope to reach a better understanding of this difference and find sex-specific diets and medicines to treat obesity-associated diseases that disproportionately affect women.”


Ovarian cancer

Anthony N. van den Pol, a professor of neurosurgery and psychiatry, aims to test a virus that is able to completely eliminate brain tumors in animals to see if it can have similar success with treating chemotherapy-resistant ovarian cancer.

“Based on our very promising preliminary data, we expect that the virus will not only selectively infect and destroy ovarian cancer cells but lead to a dramatic increase in the lifespan of test animals beyond conventional chemotherapy,” van den Pol said.

About one in every 60 women in the United States will develop ovarian cancer. It is the eighth most common form of cancer for American women and the fifth leading cause of cancer death.

In many women, ovarian cancer cells mutate and become resistant to chemotherapy, often leading to death. In collaboration with Dr. Gil Mor, professor of obstetrics, gynecology, and reproductive sciences, and Alfred Bothwell, professor of immunobiology, van den Pol plans to test a virus containing genes from Lassa and vesicular stomatitis viruses. The group hopes this virus can provide a significant development in the standard treatment of ovarian cancer.

“Even if the virus works only a quarter as well in humans as our preliminary data suggest it does against human ovarian cancer cells in mice, this could be a giant step forward in the treatment of this life-threatening malady,” van den Pol said.


Heart attacks

Dr. Erica S. Spatz, assistant professor of medicine, will test a method of classifying women who have heart attacks into more specific categories to allow for more targeted treatment based on the diverse ways in which the disease develops and is seen by medical professionals.

Every year in the United States, 40,000 women are hospitalized for acute myocardial infarction (AMI), the technical name for a heart attack, when blood flow to the heart is blocked so as to damage the muscle and potentially cause death.

Young women have a greater risk for complications and death than younger men and older women with heart attacks, but about one in five young women do not show evidence of a plaque rupture or a blood clot in an artery — the typical mechanism for causing a heart attack.

Although women have diverse presentations (i.e., symptoms) and mechanisms of disease development, they are grouped together under broad classification systems, possibly obscuring important differences and limiting research that could help reveal these variations, better inform patients about the aspects of their specific diseases, and develop more targeted treatments, Spatz said.

To help remedy this problem, Spatz and her colleagues created a system for grouping young women into five unique categories based on the various ways in which they might develop problems that lead to a heart attack. This approach could transform how medical professionals classify AMI in young women, the researchers said, but there are still questions to answer about the system’s validity for other groups of women and men.

In the new study, the team will use various patient databases to apply their classification system and assess treatment outcomes for women of different ages, races, and ethnicities and between women and men.

“For example our prior studies have shown that women of African descent more commonly present with non-classic heart attack characteristics and have worse health outcomes than women of European descent,” Spatz said. “By expanding our investigation into more diverse groups, we can advance a more personalized, precision-based approach to diagnosing and treating women who display different kinds of evidence of heart attacks.”

Since its inception, WHRY has awarded $4.8 million in annual seed grants that have gone on to generate more than $73 million in external funding.

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