Women’s Health Research at Yale funds pilot projects on debilitating and lethal diseases

Jumpstarting inventive research with major clinical implications, Women’s Health Research at Yale (WHRY) is supporting studies on vital women’s health issues via Pilot Project Program “seed” grants, as well as an inaugural Pioneer Award. These grants fund research on the verge of a significant breakthrough. This year’s grants will allow Yale researchers to:

• continue developing stem cell therapy promising a cure for hypoparathyroidism, a debilitating disease resulting from inactive hormone function of the parathyroid glands, which primarily affects women;
• design and create the first dual-purpose intravaginal ring for prevention of Human Immunodeficiency Virus (HIV) and other sexually transmitted infections, and unwanted pregnancy;
• create a revolutionary treatment model for uterine serous cancer — the most lethal endometrial cancer — that could usher in optimal, “individualized” intervention to improve survival and outcomes.

WHRY’s Pilot Project Program funds studies on women’s health and gender-specific medicine that demonstrate new approaches to major challenges in women’s health and describe a clear path to implementation for clinical or public health benefit.

The reach and productivity of the Pilot Project Program have been expanded this year with the inaugural Wendy U. and Thomas C. Naratil Pioneer Award. This new annual award was made possible by an endowment gift last year from Wendy and Tom Naratil., both of the Yale College Class of 1983. The award is for an investigation that is either highly inventive or close to a major breakthrough in advancing women’s health — where funding is needed to reach its aims.

“Our Pilot Project Program and Naratil Pioneer studies are just the kind of original, creative projects that we envision — with tremendous potential for quickly translating findings into significantly improved treatment and prevention options, some of which will be ‘personalized’ for each patient,” said Dr. Carolyn M. Mazure, the Norma Weinberg Spungen and Joan Lebson Bildner Professor of Psychiatry and Psychology, and director of Women’s Health Research at Yale.

The 2014 Pilot Project Program Awardees:

Dr. Diane S. Krause, professor of laboratory medicine, cell biology, and pathology.

Continuing the Development of Stem Cells for Therapy in Hypoparathyroidism: Thyroid cancer occurs three times more frequently in women than men. Treatment often includes the removal of the thyroid gland, and a common, unavoidable complication of surgery to remove the malignancy is removal of the nearby parathyroid glands, which are critical for calcium balance in the body. Hypoparathyroidism, which results from defects in the parathyroid glands or their removal during surgery to remove a cancerous thyroid, is a devastating disease that primarily affects women. Because patients lack the ability to regulate calcium levels in their blood, they are at risk for irregular heartbeat, debilitating muscle cramps, seizures, and other serious conditions. Treatment typically involves taking calcium, but this can prove very challenging over a long period. Krause’s research previously was funded through a WHRY pilot grant to begin development of stem cells that can be transformed into parathyroid cells. This project is to continue the inducement of stem cells to develop into parathyroid cells that would secrete parathyroid hormone to maintain normal calcium balance. Cellular replacement could hold promise for a cure.

W. Mark Saltzman, the Goizueta Foundation Professor of Chemical and Biomedical Engineering, and chair of the Department of Biomedical Engineering.

Creating a Dual-Purpose Method to Prevent Sexually-Transmitted Infections and Pregnancy: There are currently no adequate methods to protect women from the transmission of HIV and other sexually transmitted infections. Saltzman will design a new intravaginal ring (IVR) for the simultaneous prevention of sexually transmitted infections and unwanted pregnancy, using materials and methods known to be safe and expected to be acceptable to women. Saltzman brings an extensive biomedical engineering background in developing drug delivery systems using materials such as safe, ultra-tiny nanoparticles and non-toxic polymers. Specifically, he will develop an IVR that will slowly release contraceptive agents embedded within the ring and will also slowly release nanoparticles loaded with drugs to provide sustained protection against sexually transmitted infections.

Such sustained-release formulations have proven difficult or impossible to achieve with other IVR designs. Saltzman aims to overcome this challenge through the use of two independent mechanisms for releasing the different preventive agents, and using specially designed nanoparticles that will safely penetrate tissue and slowly release drugs locally. This new dual prevention method has the potential to significantly reduce the 7,000 new HIV transmissions that occur in women worldwide each day, while simultaneously providing a safe, effective method of contraception.

The inaugural Wendy U. and Thomas C. Naratil Pioneer Awardee:

Alfred L.M. Bothwell, professor of immunobiology.

“Personalized Medicine” for the Most Lethal Endometrial Cancer: Endometrial cancer is the most common gynecological cancer in the United States, with approximately 50,000 new cases and more than 8,000 deaths annually. Uterine serous cancer, a particularly aggressive form, accounts for 10% of endometrial cancer cases, but is responsible for nearly 40% of endometrial cancer deaths. Thus, new, more effective treatment strategies are needed. Bothwell will tackle this challenge by developing an innovative mouse model of uterine serous cancer that more closely simulates a patient’s experience than existing models by integrating the patient’s immune system and tumor pathology. This model promises to usher in “personalized medicine,” allowing treatments to be tailored and optimized for individual patients. Specifically, Bothwell will test, for the first time, how drugs or drug combinations interact simultaneously with immune response, tumor response, and genetic factors. Because uterine serous cancer spreads quickly, the evaluation of therapies must be completed as rapidly as possible to benefit patients. This experimental model will allow evaluation much faster than would be possible in human clinical trials, thus providing clinical benefit.

Women’s Health Research at Yale was founded in 1998 to address disparities in medical research by initiating and supporting never-before-undertaken studies on the health of women and gender-specific aspects of health and disease. The center has since grown into one of the largest interdisciplinary research centers of its kind in the country and has become a national model.

Since its inception, WHRY has awarded more than $4.6 million in annual pilot grants to more than 70 investigators who have obtained more than $52 million in external grants to further their research.

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