Awardees & Updates – 2019

Understanding the impact of estrogen receptor mutations on hormone-responsive gynecologic malignancies.
Stephanie Gaillard, MD, PhD; Assistant Professor, Oncology, Obstetrics & Oncology, Johns Hopkins University School of Medicine

The majority of advanced gynecologic cancers are treated with systemic chemotherapy, however, an improved understanding of the molecular drivers of tumor cell growth has shown that a subset of gynecologic cancers is dependent on hormone signaling pathways, especially estrogen and progesterone. Emerging data suggests that hormone suppressive therapies, or endocrine therapy, can be used to treat such cancers and may even eliminate the need for systemic chemotherapy. This study could have immediate clinical impact by determining the metrics to provide predictive and prognostic individualized patient data in real-time as well as identify potential combination therapies to be evaluated in future clinical trials.

The role of neuroactive steroids in premenstrual dysphoric disorder.
Alison Kimball, endocrine fellow, Massachusetts General Hospital, Harvard Medical School

Premenstrual dysphoric disorder (PMDD) is a psychiatric condition characterized by five or more emotional and physical symptoms including depression, anxiety, irritability, fatigue and bloating in the luteal phase of the menstrual cycle. Both PMDD and premenstrual syndrome are highly prevalent, experienced by nearly 50% of women worldwide. PMDD is associated with substantial morbidity and functional impairment, but there are few effective therapies. Neuroactive steroids are metabolites of sex steroids; the best studied is the progesterone metabolite allopregnanolone. Previous studies on allopregnanolone levels in women with PMDD have shown conflicting results even though low levels have been shown to correlate with depression. This study will utilize new technology to more accurately measure allopregnanolone levels at different phases of the menstrual cycle providing new information for effective new treatments for PMDD.

Effects of estrogen and growth hormone on the adipose tissue secretome.
Armen Yerevanian, endocrine fellow, Massachusetts General Hospital, Harvard Medical School

Estrogen promotes fat storage in healthier subcutaneous regions of the body rather than in the abdominal region where fat stores are more associated with disease. Growth hormone (GH) promotes preservation of muscle mass and loss of abdominal fat. Estrogen and GH work together to promote the loss of metabolically harmful abdominal fat, however, research shows that estrogen actually blocks GH action. How do researchers reconcile these two phenomena? This study will test the hypothesis that novel proteins, known as secretome, are modulating the interaction of GH and estrogen in adipose fat. This could help identify targets for changing the dynamics of abdominal fat accumulation and create female specific treatments for obesity and metabolic syndrome.