VINCENT CENTER FOR REPRODUCTIVE BIOLOGY


From the Lab

Laboratory science is at the heart of research conducted in the Vincent Center for Reproductive Biology (VCRB), where teams of scientists work to understand how cells and genes work, what goes wrong in various OB/GYN conditions, and how to amend the complex signaling pathways involved. Below is a sampling of laboratory research conducted by VCRB investigators.

Emerging Therapies for Ovarian Cancer

Emerging Therapies for Ovarian Cancer

Oladapo Yeku, MD, PhD, FACP, is among a team of scientists in the VCRB who are studying one of the most difficult malignancies to treat — ovarian cancer — which causes more deaths than any other cancer of the female reproductive system and annually kills 14,000 women in the United States. A major focus of his work is immunotherapy, harnessing the tumor-killing power of the immune system. But immunotherapy for the management of ovarian cancer has unique challenges, due to the diverse population of cells involved and a lack of antigens to target. Adding to the complexity, scientists also are dealing with a hostile tumor microenvironment, consisting of a variety of resident and infiltrating host cells, secreted factors and extracellular matrix proteins. To accelerate drug development and improve patient outcomes, novel immunotherapeutic approaches are needed that are informed by an understanding of ovarian cancer biology. Dr. Yeku’s lab is studying a cell-surface protein called MUC16 and its role in ovarian cancer tumorigenesis and how it evades the immune evasion, in collaboration with medical oncologist David Spriggs, MD, director emeritus of the Gynecologic Medical Oncology Program at the Mass General Cancer Center. Answers are emerging. The Spriggs lab has shown MUC16 regulates growth, invasion and metastatic disease through the structure of sugars (glycosylation) on the surface of normal and cancer cells. This regulation requires interaction with specialized sugar-binding proteins called galectins, key components of the tumor microenvironment. VCRB scientists now are actively developing antibodies against MUC16 and Galectin-3 for diagnosis, imaging and treatment of ovarian cancer. To date, their work has shown that antibodies that inhibit cell-to-cell interactions can slow tumor growth and inhibit metastasis. They have developed a suite of therapeutic approaches designed to exploit MUC16 expression. In addition, in preclinical tumor models, they are working to understand how the immunosuppressive tumor microenvironment undermines these therapies in ovarian cancer and prospectively engineering solutions to these problems in anticipation of launching clinical trials.

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How Ovarian and Uterine Cells Become Malignant

How Ovarian and Uterine Cells Become Malignant

Bo Rueda, PhD, has a broad background in basic, translational and clinical research focused in the field of women’s reproductive health. More specifically, he has significant expertise in the areas of reproductive and cancer biology, with an emphasis on ovarian and uterine function and benign and malignant transformation of the cells in these organs. In addition to his role as a scientist, Dr. Rueda serves as the director of the Vincent Center for Reproductive Biology (VCRB), executive director of the Mass General OB/GYN­–based tissue repository, and director of the Vincent Department of Obstetrics and Gynecology VCRB Clinical Fellows Research Program, in which he is responsible for fellows’ research and training in multiple disciplines including Reproductive Endocrinology and Infertility, Maternal-Fetal Medicine and Gynecologic Oncology. He also advises or assists in the development of hypothesis-driven or hypothesis-generating basic, translational and clinical research that reflects the interests of graduate students, postdoctoral and clinical fellows, and junior and senior faculty within and outside the Vincent Department of OB/GYN. In 2017, he was appointed chair of the newly formed MGH Committee on Fundamental Research, which provides a forum for fundamental primary research investigators to actively engage in developing solutions to improve Mass General Brigham policies, infrastructure and environment to benefit the research community. In 2022, he was named the inaugural incumbent of the Endowed Chair in Reproductive Biology, funded by the VMHF.

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Innovative Ways to Combat Ovarian and Cervical Cancers

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.

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Preventing Preterm Birth

Preventing Preterm Birth

Mark Phillippe, MD, MHCM, an OB/GYN subspecialist in Maternal-Fetal Medicine, is elucidating the mechanisms responsible for the onset of labor (parturition), including those responsible for preterm childbirth. In previous research, he identified associated factors such as the presence of intrauterine inflammation, hemorrhage and infection, including increased maternal morbidity and mortality during severe influenza outbreaks. Since joining the VCRB in 2012 as a senior investigator, he has been addressing the novel hypothesis that cell-free fetal DNA (cffDNA) functions as a signal to trigger the spontaneous onset of childbirth (parturition). His findings suggest that the release of cffDNA into the maternal plasma may be occurring in response to the progressive shortening of structures at the end of chromosomes (telomeres) in specialized cells of the placenta called trophoblasts, which initially play a role in embryo implantation and continue interacting with the mother’s uterus during pregnancy. He has demonstrated that an increase in cffDNA activates a sequence of pro-inflammatory signaling events, resulting in spontaneous birth. He is seeking to identify the specific triggers of these inflammatory events in the absence of microbial invasion and intrauterine infection, with the goal of developing new therapeutic interventions for various complications of pregnancy, including preterm birth and post-dates gestation.
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