VINCENT CENTER FOR REPRODUCTIVE BIOLOGY
Into the Clinic
In translational research, investigators work to find solutions in the lab, then translate these findings into novel treatments offered to patients in clinical studies. Results of these clinical trials are used to define future patient treatments. Below is a sampling of clinical studies emerging from findings initially made in the VCRB laboratory.
Role of Microbes in Women’s Vaginal Health
Caroline Mitchell, MD, MPH, a VCRB investigator, is studying how microbial changes in the vagina and urinary tract lead to health complications across the lifecycle of women. The human vagina is normally dominated by one bacterial species — Lactobacillus. When that population is disrupted by the emergence of other types of bacteria, it causes bacterial vaginosis. Symptoms range from the unpleasant including vaginal itching, odor or discharge, to the far more serious including increased risk of contracting sexually transmitted infections, difficulty conceiving, and higher risk of premature delivery and low birth-weight. Her research has shown these more serious complications are caused by inflammation, for which she is seeking treatments. To that end, Dr. Mitchell is working to develop an in vitro model of vaginal tissue to allow pre-clinical testing of new therapies. In collaboration with colleagues at the Ragon Institute, she used an early version of this model to help confirm the inflammatory potential of certain vaginal bacteria associated with a higher risk of acquiring HIV. Among recent clinical studies, she compared three options to relieve postmenopausal vaginal discomfort — a low-dose estrogen vaginal tablet, a nonprescription moisturizer, and a placebo gel — and found similar improvements for all three groups, pointing to the need to understand the underlying biology of what causes symptoms. Her lab is currently analyzing biologic samples from that study to help explain the results. At the other end of the lifespan, she is working with investigators at the Broad Institute to better understand how the vaginal microbiota of pregnant women influence the infant gastrointestinal microbiome, as prior studies have shown that being born vaginally leads to a different gastrointestinal bacterial community than being born via C-section.
- Efficacy of vaginal estradiol or vaginal moisturizer vs. placebo for treating postmenopausal vulvovaginal symptoms: a randomized clinical trial.
- Lactobacillus-deficient cervicovaginal bacterial communities are associated with increased HIV acquisition in young South African women.
- Vaginal microbiota and genitourinary menopausal symptoms: a cross-sectional analysis.
Next Generation of Targeted Cancer Therapies
Whitfield Growdon, MD, focuses on defining targets for novel cancer therapies in the laboratory, then bringing those new therapies to patients in clinical trials. As a surgeon in the Division of Gynecologic Oncology, Vincent Department of OB/GYN at Mass General, he provides surgical care for patients with cervical, endometrial and ovarian cancer, including innovative techniques such as robotic surgery and single-incision laparoscopy. As a VCRB investigator, he works within an interdisciplinary team to discover the molecular signatures of gynecologic cancers, striving to identify subpopulations of patients that may benefit from specific therapies. His investigations focus on rare cancers, such as vulvar cancer and carcinosarcomas, and more common tumors such as endometrial and ovarian cancer. Recently, he identified genetic variants and signaling pathways involved in a high-grade form of endometrial cancer called uterine serous carcinoma, showing that it harbors HER2 gene amplification and HER2 protein overexpression. Based on these results, patients are now being accrued for a clinical trial using an irreversible inhibitor of HER2.
- Characterization of immune regulatory molecules B7-H4 and PD-L1 in low and high grade endometrial tumors
- Ridaforolimus improves the anti-tumor activity of dual HER2 blockade in uterine serous carcinoma in vivo models with HER2 gene amplification and PIK3CA mutation.
- The therapeutic challenge of targeting HER2 in endometrial cancer.