VINCENT CENTER FOR REPRODUCTIVE BIOLOGY
New Research Faculty
The VCRB recently welcomed two new investigators, highlighted below. Today, seven investigators perform research in the VCRB laboratory, working closely with more than 70 physicians in the Vincent Department of OB/GYN as well as other scientists at Massachusetts General Hospital, an affiliate of Harvard Medical School.
Innovative Ways to Combat Ovarian and Cervical Cancers
Cheng Wang, PhD, who joined the VCRB research team in July 2017, focuses on uncovering the cellular and molecular mechanisms underlying the development of ovarian and cervical cancers. Ovarian cancer is the most lethal gynecologic cancer in the United States. Cervical cancer is the most common gynecologic cancer and the leading cause of cancer death in women worldwide. Specifically, his team is looking at the role of the Hippo signaling pathway in the development of ovarian and cervical cancers. When functioning normally, this pathway suppresses tumors. But disruptions in this pathway can lead to malignant transformation of ovarian and cervical cells. Dr. Wang’s team is looking at what leads to the disruption of the Hippo pathway in cells lining the fallopian tube, why cells with a disrupted Hippo pathway become transformed, and how the transformed cells colonize in the ovary and surrounding tissues to form high-grade serous cancers. His team also is studying the interaction between the Hippo pathway and the high-risk human papillomavirus to see if their “crosstalk” is involved in the onset and/or progression of cervical cancer. In addition, they are actively seeking novel ways to preserve fertility of young female cancer survivors who have been treated with lifesaving chemotherapy and radiation.
- The Hippo/YAP pathway interacts with EGFR signaling and HPV oncoproteins to regulate cervical cancer progression.
- YAP forms autocrine loops with the ERBB pathway to regulate ovarian cancer initiation and progression.
- YAP induces high-grade serous carcinoma in fallopian tube secretory epithelial cells.
Role of Maternal Obesity in Brain Deficits in Offspring
Andrea Edlow, MD, MSc, an OB/GYN subspecialist in Maternal-Fetal Medicine who joined the VCRB in November 2017, is studying how maternal obesity influences fetal brain development and the behavior of offspring. Population studies have shown the offspring of obese women are at increased risk for autism, ADHD, anxiety, depression and neurodevelopmental delay, but the underlying mechanisms have been largely unknown. Her lab was one of the first to use amniotic fluid and umbilical cord blood to study real-time brain development in fetuses of obese pregnant women. She found the genes expressed in these biofluids were associated with increased inflammation and impaired regulation of processes needed for normal brain development. Working in obese pregnant mouse models, she now is examining fetal brain tissue, the levels of neurotransmitters and the neurobehavior of their offspring, that is, how quickly they learn to find a platform in a pool of water or how social they are when presented with an unfamiliar mouse. Preliminary findings suggest that maternal obesity has sex-specific effects on the offspring: Males are more likely to have certain prenatal brain changes that correspond with learning and memory deficits as adults, while females are more likely to have abnormal neurotransmitter signaling in brain regions that control eating throughout the lifespan and are more likely to become obese themselves. Dr. Edlow hopes this work will ultimately provide targets for lifestyle interventions and prenatal drug therapies for obese pregnant women to potentially reverse or ameliorate harmful changes that may occur in the fetal brain.
- Assessing the fetal effects of maternal obesity via transcriptomic analysis of cord blood: a prospective case-control study.
- Males are from Mars, females are from Venus: sex-specific fetal brain gene expression signatures in a mouse model of maternal diet-induced obesity.
- Maternal obesity affects fetal neurodevelopmental and metabolic gene expression: a pilot study.