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Current Scholars

Jacqueline Parchem (2019-2022)
Award: SMFM/AAOGF Scholar
Site of Research: University of Texas
Title of Research: Modulation of Neural Tube Closure by Amniotic Fluid Exosomes

Neural tube defects (NTDs) are devastating birth defects that result from failure of neural tube closure during early fetal development. In spina bifida, trauma to the exposed spinal cord results in irreversible neurologic injury. Despite advances in fetal surgery, the majority of children remain unable walk and have lifelong disability. Therefore, innovative prenatal interventions have the potential to reduce residual deficits children with NTDs. To identify mechanisms governing neural tube closure and neural injury in NTDs, our study focuses on the role of amniotic fluid (AF) exosomes. Exosomes are naturally-occurring nanovesicles in the AF that facilitate cell communication through the exchange of molecular messages. While exosomes have been shown to be important for a number developmental and disease processes, the role of AF exosomes in fetal neurodevelopment is unknown. We will use a combination of in-depth molecular analyses of human AF samples and experiments in mice and cell culture to test our central hypothesis that AF exosomes modulate neural tube development and injury in NTDs. We will further test an innovative prenatal treatment strategy to determine the potential of exosome-based fetal therapy.
 


Mark Clapp (2019-2022)
Award: American Board of Obstetrics & Gynecology/AAOGF Scholar
Site of Research: Massachusetts General Hospital
Title of Research: Development of an EHR-based Obstetric Risk Score

Accurate methods for risk stratification in obstetrics are essential to anticipate and prepare for potential intrapartum complications. Furthermore, risk stratification can help to ensure that patients are cared for by the appropriate provider and at the appropriate facility. Currently, few methods exist for risk stratification in pregnancy. This research project will use the vast data collected in the electronic health record (EHR) to predict severe maternal morbidity during labor and delivery. As EHR data are gathered in large quantities and in real-time by most health care institutions, the long-term goal for this research is to develop and incorporate EHR-based tools to aid in clinical decision-making and risk recognition for providers, ultimately reducing pregnancy-related morbidity and mortality.
 


Rebecca Previs (2019-2022)
Award: GOG Foundation/AAOGF Scholar
Site of Research: Duke University
Title of Research: Immune Modulation of CaMKK2 in the Ovarian Tumor Microenvironment

The treatment of ovarian cancer includes a combination of surgery and chemotherapy. Although the majority of women initially respond to treatment, the likelihood of cancer progressing remains high. When this occurs, physicians treat patients with chemotherapy with modest success rates. An urgent need exists to treat ovarian cancer patients with better, lifesaving options when our current therapies are not enough. Often ovarian cancer cells, like other types of cancer, escape recognition by the bodies' natural defense system, the immune system. The immune system consists of multiple different cell types that assist in recognition of foreign cells, like cancer cells. Other cells, called T-cells, are devoted to attacking these foreign cells. In other tumor types, like melanoma, therapies are geared toward enhancing the way the immune system works to combat cancer cells. Clinical trials for this type of treatment or immunotherapy are ongoing for ovarian cancer patients. This study evaluates the role of CaMKK2, which has been observed overexpressed in the tumor cells of ovarian cancer patients whose cancer tends to recur sooner. It is also known to be expressed on several types of immune cells. We seek to modulate CaMKK2 and better understand its role within ovarian cancer and cancer-associated immune cells. The data generated by this proposal will provide the rationale for manipulating CaMKK2 in patients to make their immune system more effectively recognize foreign ovarian cancer cells, and consequently, make their cancer more responsive to therapies.
 


Nandini Raghuraman, MD (2018–2021)
Award: Foundation for SMFM/AAOGF Scholar
Site of Research: Washington University
Title of Research: Risks of intrapartum maternal oxygen supplementation: mechanisms for harm in the mother and neonate

Intrapartum oxygen (O2) supplementation for Category II fetal heart tracings is nearly ubiquitous on Labor and Delivery units, with over 60% of laboring women in the U.S. receiving supplemental O2 at some point during labor. This practice has become standard of care, yet there is no evidence of benefit and even concern for possible harm via free radical production. Hyperoxygenation in the neonate is associated with adverse outcomes such as retinopathy, bronchopulmonary dysplasia, and abnormal neurodevelopment. Similar harm has been demonstrated in adults including increased ICU morbidity from excess oxygen exposure. This calls for a closer look at the effect of intrapartum oxygen exposure on the fetus. We plan to conduct a randomized controlled trial of maternal oxygen supplementation versus room air in patients with Category II fetal heart tracings in labor. The primary objective of this study is to investigate the effect of intrapartum oxygen exposure on maternal and umbilical cord malondialdehyde, a free radical-mediated marker of oxidative stress. We will also collaborate with pediatric neurology to use magnetic resonance diffusion tensor imaging to study the effect of intrapartum hyperoxia on the neonatal brain.
 


Lauren Theilen, MD (2018–2021)
Award: American Board of Obstetrics & Gynecology/AAOGF
Site of Research: University of Utah Health/Intermountain Healthcare
Title of Research: Modifiable cardiovascular risk and cardiovascular morbidity following recurrent hypertensive disease of pregnancy

Women who have had hypertensive disease of pregnancy (HDP) in more than one pregnancy have significantly increased risks for death from heart disease and stroke before the age of 50; however, based on current guidelines, many of these women may not initiate screening for cardiovascular risk factors before age 45. We hypothesize that women with a history of recurrent HDP will develop detectable, modifiable cardiovascular risk factors within 10-15 years of their first affected pregnancy. To test this hypothesis, we will identify women with recurrent HDP who delivered their first affected pregnancy 10-15 years ago (exposed women) and match them to a group of women who also had more than one pregnancy, but who had no history of HDP in any of their pregnancies (unexposed women). We will screen both groups of women for modifiable cardiovascular risk factors, and we will compare the incidence of these risk factors among exposed and unexposed women. Women who are identified as having increased risk for cardiovascular disease will be referred to an appropriate healthcare provider for further evaluation and treatment. Additional information will be collected on an annual basis from subsequent visits to primary care providers to allow ongoing collection of data regarding cardiovascular risk and health outcomes. We will also perform a retrospective study using medical records to determine rates of cardiovascular disease (coronary artery disease, myocardial infarction, and stroke) among women with a history of recurrent HDP. Our study will provide much-needed information that may inform new screening strategies to improve long-term health among women.
 


Anne Van Arsdale, MD, MSc (2017-2020)
Award: American Board of Obstetrics and Gynecology/AAOGF
Site of Research: Montefiore Medical Center/Albert Einstein College of Medicine
Title of Research: Mapping HPV Integration in precancerous cervical lesions

Infection with a high-risk variant of human papilloma virus (HPV) is a well-established, key event in the development of cervical carcinoma. One consequence of HPV infection is expression of virally encoded oncogenes that drive cell proliferation, most notably those encoding the E6 and E7 proteins. Integration of the HPV DNA into the human genome is a second consequence that has recently emerged as a ubiquitous factor in tumorigenesis that 1) stably associates the viral oncogenes with a host cell, 2) likely drives expression of host oncogenes that flank the sites of HPV DNA insertions, and 3) also causes human genome instability. Identification of HPV DNA integration events early in the disease process and assessment of their impact on temporal progression of cervical dysplasia may provide potential risk stratification criteria for women at the time of incident screening. While use of next generation sequencing (NGS) methods have significantly advanced our understanding of the consequences of HPV DNA integration, understanding the precise patterns and potential consequences of integration, particularly in the early stages leading to cervical neoplasia, remains a significant void in our knowledge. A major, current, shortcoming in clinical management of early cervical dysplasia is the inability to assess which lesions will be among the small fraction that progress to full-blown, invasive neoplasia, thus precluding limiting treatments with significant morbidity risks to only those at substantial risk.

To fill this significant gap, we have developed a custom-designed hybridization capture NGS approach designed to enrich for HPV DNA and detect viral integration events present in only a small fraction of cells in early lesion tissue samples. In pilot data, our method has proved remarkably sensitive, identifying all previously validated integration sites in well-characterized cell lines, along with 3 fold novel integration sites in both cell lines and pre-invasive clinical samples. I hypothesize that integration of HPV DNA is a crucial step in progression of early lesions to full-blown, invasive carcinomas and that clonal expansion of cells with integrations adjacent to cellular oncogenes is a key marker of disease progression in precancerous CINs. Building on my results, I propose to study HPV integration events throughout the time course of disease, monitoring the spatio-temporal relationships of integration events and their clonal expansion from early stage cervical lesions to cervical cancer and to determine at the genome and transcriptional level the effects of integration events. To accomplish this, I will use samples in our clinically well-annotated tissue biorepository from women with incident cervical dysplasia or carcinoma who were followed longitudinally. The ultimate goal of this project is to identify integration events that help predict progression of cervical dysplasia, thus serving as a personalized biomarker in stratifying women at the time of screen screening.
 


Jennifer Gilner – (2016-2019)
Award: Pregnancy (SMFM) Foundation/AAOGF Scholar
Site of Research: Duke University
Title of Research: The Role of Regulatory T Cells in the Maternal-Fetal Rejection Phenotype of Preterm Birth.

Pregnancy represents a unique natural allograft scenario in which immunologically mismatched organisms must tolerate direct apposition, yet maintain immunologic activity against external pathogens. This is analogous to organ transplantation, where tolerance of the grafted organ (and its foreign antigens) requires active regulation of immune responses. T Regulatory cells (or “Tregs”) are a unique subpopulation of CD4+ lymphocytes that play a critical role in establishing immune tolerance and therefore preventing allograft rejection. In the case of pregnancy, the fetus represents a foreign graft, and immune rejection may lead to adverse pregnancy outcomes such as preterm birth. Given the biologic parallels between organ transplantation and pregnancy, we hypothesize that Tregs play a parallel role in pregnancy; specifically to induce tolerance in the mother, and prevent rejection which could lead to preterm birth. To date, regulatory T cell function has only been studied in the broadly defined “spontaneous” or “medically indicated” preterm birth cohorts. We propose to focus on the cohort of preterm births with a molecular phenotype of maternal anti-fetal rejection, given that Treg suppressive function is well established as a critical mechanism in maintenance of alloimmune tolerance. This innovative approach will allow for a careful characterization of the molecular immunology of affected pregnancies, and will be critical to the development of targeted detection and treatment strategies for reducing the burden of preterm birth.
 


Jose Alejandro Rauh-Hain – (2016-2019)
Award: American of Obstetrics and Gynecology/AAOGF Scholar
Site of Research: Massachusetts General Hospital
Title of Research: Trends in First-line Treatment and Spending on Care for Women with Epithelial Ovarian Cancer

The United States spends over US $2.2 trillion (16% of national budget) on healthcare. In particular, cancer treatment accounts for an increasing amount of national health expenditures; including rising costs of new chemotherapy/biologic agents. In this context, cost analysis is paramount in order to measure the disease-specific economic burden and predict the impact of novel medical interventions. The costs associated with cancer treatment must consider both the costs of treatment but also the cost of managing disease progression or recurrence as well as the cost of treatment-related toxicity. Ovarian cancer is the fifth leading cause of all cancer-related deaths among women. Despite the fact that ovarian cancer is the most lethal gynecologic malignancy, little information is available about the cost of treatment after the diagnosis of ovarian cancer. Ovarian cancer treatment in particular is susceptible to rising costs due to the constant influx of novel chemotherapeutics and biologics, most of which are more costly than the established front-line therapies but have limited proven benefit. The costs associated with care of ovarian cancer patients are considerable and are highest during the first year of diagnosis and the last year of life. The overall objective of this project is to determine the direct medical cost of primary ovarian cancer treatment and related complications, and to estimate contribution of different therapeutic modalities and health care services to total spending on ovarian cancer care using the Premier Perspective database.
 

AAOGF News

2018 Bridge Grant Recipients

Jesus Gonzalez Bosquet, MD, Ph.D.

Shannon Michelle Hawkins, MD


Emily Miller, MD MPH

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2018 Travel Award Recipients

Mae Wu Healy, DO, FACOG, LCDR, MC, USN
Uniformed Services University of the Health Sciences
Donald Swartz Award

David Bryan Nelson, MD
University of Texas Southwestern Medical Center
Walter T. Dannreuther Award

Beri Melissa Ridgeway, MD
Cleveland clinic
Henry L. Darner Award

Katina Robison, MD
Women and Infants Hospital Rhode Island
AGOS President's Award

Malgorzata E. Skaznik-Wikiel, MD
University of Colorado Denver
James W. Kennedy Award

Amanda Cofer Yunker, DO, MSCR, FACOG
Vanderbilt University Medical Center
J Bay Jacobs Award

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