Current Scholars
Beth L. Pineles, MD, PhD (2024 – 2027)
Award: SMFM/AAOGF Scholar Award
Site of Research: Perelman School of Medicine of the University of Pennsylvania
Title: Deimplementation of Ineffective and Harmful Medical Practices: A Data-Driven Commentary
David Huang, MD, PhD (2024 – 2027)
Award: ABOG/AAOGF Scholar Award
Site of Research: University of California, San Francisco
Title: Elucidating the Transcriptomic Landscape of the Human Endometrium at a Single-cell Level During the Window of Implantation: Understanding How Aberrant and Artificial Endometrial States Contribute to Adverse Pregnancy Outcomes
Melissa S. Wong, MD, MHDS (2023 – 2026)
Award: SMFM/AAOGF Scholar Award
Site of Research: Cedars-Sinai Medical Center
Title: Using Artificial Intelligence (Machine Learning) to Build an Integrated Real-Time Delivery Predictor
The goal of the current proposal is to evaluate the ability of a machine learning model (Partometer), which can predict in real time the probability of a vaginal delivery during labor, to increase rates of vaginal delivery. The aim of this project are as follows: (1) to compare predictions of the Partometer prospectively to those made by clinicians in real-time (2) to engage clinician stakeholders to refine the final version of the Partometer for imple-mentation, and (3) to activate the Partometer for clinical use and evaluate the feasibility of a prospective trial using the Partometer to increase rate of vaginal delivery. Understanding both how to study the effectiveness and optimal implementation of AI in caring for pregnant patients will be critical as obstetric care continues to grow more complex, and concerns about unequal treatment more transparent. Receiving the described training will lay the groundwork for a career focused on using artificial intelligence to improve maternal and newborn birth outcomes and reduce disparities in maternal care.
Maria Florian-Rodriguez, MD (2022-2025)
Award: AAOGF and Burroughs Wellcome Fund Physician-Scientist Career Development Award to Promote Diversity
Site of Research: UT Southwestern Medical Center
Title: Cellular Senescence as an Underlying Mechanism for the Development of Pelvic Organ Prolapse
Pelvic organ prolapse (POP) (defined as descent of the anterior vaginal wall, posterior vaginal wall, uterus, or apex of the vagina (1)) is a common condition in aging women (2). The public health impact is enormous. Women have a lifetime risk of undergoing surgery for this condition of up to 13% (3). POP greatly affects quality of life, resulting in social isolation and overall health decline (4). Furthermore, it is estimated that direct costs associated with POP surgery are close to 1 billion dollars per year (5). The increased prevalence with age suggests that POP is an age-related disorder with the most common risk factor being vaginal parity. As our population continues to age, POP prevalence and associated costs will continue to increase, underscoring the need to better understand its pathogenesis and develop new preventative and treatment options.
On a cellular level, the process of aging is termed cellular senescence (6, 7). Senescent cells secrete proinflammatory and matrix degrading molecules in what is known as the Senescent Associated Secretory Phenotype (SASP) (8). Accumulation of senescent cells and SASP factors lead to impaired tissue regeneration underlying age-dependent onset of many degenerative diseases in non-reproductive tissues (6, 9-16). The role of cellular senescence in loss of pelvic organ support with age, however, has not been explored.
Based on recently published data, preliminary experimental data, and the fact that induction of protease activity plays a major role in senescence, we propose the novel hypothesis that injury-induced initiation of cell senescence at the time of vaginal delivery culminates in pelvic organ prolapse during aging. Support may be maintained for years as compensatory mechanisms mask development of prolapse (for example regeneration, elastogenesis, and pelvic muscle strength). Nevertheless, if damage or injury is severe, or if the host response to injury is impaired, we hypothesize that evolution of cell senescence will manifest with aging. Our preliminary data demonstrates (i) increased cell senescence in vaginal stromal tissues from women with prolapse, and (ii) increased markers of senescence in the vaginal wall prior to the development of POP in an animal model of prolapse. Further, we present new preliminary studies that we can genetically cure agedependent POP inherent to Fbln5-/- mice by knocking out the Cyclic GMP-AMP Synthase (cGAS) pathway. Gene products in the cGAS pathway are essential for cellular senescence. Thus, these results provide important new information that cGAS-mediated cellular senescence plays a fundamental role in the development of POP. In this study, we will test our hypotheses using animal models which allow for longitudinal follow up that is not feasible in humans.
Melissa Frey, MD (2023 – 2026)
Award: ABOG /AAOGF Scholar Award
Site of Research: Weill Cornell Medicine
Title: Randomized Controlled Trial of Facilitated Cascade Testing for BRCA1/2 Mutations
More than two decades since the discovery of genetic predisposition to breast and ovarian cancer, the promise of genomics as a tool for cancer prevention has yet to be fully realized. While approximately one million adults in the US carry BRCA1/2 mutations, fewer than 20% know that they are carriers. Furthermore, racial and ethnic minorities and those with low socioeconomic status experience marked under-recognition of hereditary cancer syndromes, leading to late or missed diagnoses. Ideally, when a person is found to carry a BRCA1/2 mutation, this information is “cascaded” or shared with at-risk relatives, so they too can seek genetic testing and ultimately adopt life-saving cancer surveillance and risk reduction interventions. However, under the current medical system, carriers of a BRCA1/2 mutation must shoulder the burden of organizing cascade testing for their relatives, leading to alarmingly low rates of testing. In a pilot study, we found that clinician-facilitated cascade testing through telephone genetic counseling and mailed saliva kit testing resulted in cascade testing for approximately 60% of relatives, an uptake rate significantly higher than reported in the literature. Through this research, we seek to evaluate clinician-facilitated cascade genetic testing compared to standard of care in a multi-institutional randomized controlled trial and to assess clinical and demographic features (e.g., race, ethnicity, education, affordability, social determinants of health) associated with inequity in use of cascade genetic testing.
Molly McAdow, MD, PhD (2022 – 2025)
Award: SMFM/AAOGF Scholar Award
Site of Research: Yale University School of Medicine
Title: The Role of Plasminogen Inhibitors in Endothelial Dysfunction in Preeclampsia
Preeclampsia affects 8% of pregnancies worldwide and is characterized by widespread endothelial dysfunction. There is no specific therapy for preeclampsia. Nitric oxide is a critical vasodilatory substance produced in endothelial cells by endothelial nitric oxide synthase (eNOS). Chemical inhibition or genetic manipulation of eNOS in animal models causes hypertension in pregnancy. Recent work by our laboratory has identified that exogenous plasminogen activator inhibitor 1 (PAI-1) physically interacts with and inhibits eNOS in endothelial cells. Maternal plasma PAI-1 levels rise over the course of normal pregnancy and increase more rapidly and to a greater extent in pregnancies affected by preeclampsia. PAI-2, a structurally similar molecule, is not found in plasma of non-pregnant individuals but is abundant in the third trimester of normal pregnancies. Interestingly, its circulating levels are suppressed in preeclampsia.
Predicated on these observations is the hypothesis that the interactions between PAI-1, PAI-2, and eNOS contribute to the pathogenesis of preeclampsia. We will investigate this hypothesis by defining the mechanisms of PAI-1-dependent eNOS inhibition and will use a translational approach to investigate whether these interactions could contribute to the maternal syndrome of preeclampsia. Second, we will explore whether PAI-2 interacts with or inhibits eNOS using biochemical and imaging approaches. Lastly, we will investigate whether these interactions are involved in the origins of preeclampsia at the maternal-fetal interface. Elucidating the activities of PAI-1 and PAI-2 and their interplay in pregnancy will help to better understand the molecular mechanisms of hypertensive disorders of pregnancy and may lead to novel therapeutic targets.
Robert Hillman, MD, PhD (2022 – 2025)
Award: GOG Foundation /AAOGF/Clovis Scholar Award
Site of Research: MD Anderson Cancer Center
Title: Liquid Biopsy Detection of Structural Variant Breakpoints to Monitor Ovarian Cancer Clonal Evolution
It has long been known that ovarian cancers shed portions of their DNA into the bloodstream of affected women, and that sensitive methods can be used to detect this tumor DNA from blood samples. The research proposed in this study will develop a novel method for individually detecting rare populations of tumor cells from the bloodstream of women with ovarian cancer in order to longitudinally detect tumor evolution in real-time. This approach will rely on a key observation that the genomes of ovarian cancer are frequently rearranged, meaning each tumor has numerous “breakpoints” from two or more distant locations that are brought together. Since these “breakpoints” both identify tumor cell sub-populations and by definition do not occur in normal cells, the key insight of this proposal is that “breakpoint” detection from blood samples is an innovative and powerful approach to detecting ovarian cancer tumor evolution from blood samples.
This research has the potential to result in a completely new paradigm for monitoring ovarian cancer response to treatment. Rather than waiting for treatment completion to assess response, a woman and her doctor could observe her tumor’s evolution in real-time and personalize treatment decisions based on this information. The early detection of emerging tumor resistance could lead to earlier changes in treatment and improvement in survival outcomes. Importantly, this novel approach to monitoring tumor evolution is a broadly applicable technology that could be used across tumor types.
Shuk On Annie Leung, MD (2022 – 2025)
Award: AAOGF/ABOG Scholar Award
Site of Research: McGill University Health Centre
Title: Development of a Point-of-Care Ultrasensitive Assay for the Identification of High-Grade Cervical Dysplasia and Cervical Cancer
Cervical cancer is the fourth most commonly diagnosed cancer among women worldwide. With the discovery that human papillomavirus (HPV) is the primary cause of cervical cancer, many screening programs are transitioning to primary HPV testing because of its enhanced diagnostic sensitivity and less resource-intensive nature. However, HPV testing is less specific at detecting cervical cancer than Pap smears, resulting in unnecessary colposcopy referrals and overtreatment of non-cancerous lesions. While recent advances have identified protein biomarkers with improved specificity that could be used to complement HPV testing, standard protein-detection equipment is restricted to specialized laboratories. Collectively, this illustrates a need for an accessible and improved screening strategy to triage HPV-positive patients at highest risk of cervical cancer, which forms the basis of my research program. A panel of protein biomarkers that is sensitive and specific for cervical dysplasia and cancer will be identified using the ultrasensitive protein detection method of Single Molecule Array (Simoa). Next, to increase accessibility of the Simoa technology, it will be translated onto a portable point-of-care (POC) device by leveraging on existing microfluidic engineering technology. Finally, the design of the proposed POC device will be informed by the iterative ‘systems design engineering process’, which is built upon feedback collected during interviews and focus groups with stakeholders. Whereas laboratory-based protein detection is well-established, our solution would represent the first-of-its-kind device that leverages microfluidics-based engineering to enable improved and accessible detection of cervical sample biomarkers.