The Galas Project
Unveiling the Complexities of Pregnancy: Genetics and Stress in Diverse Communities
Maternal and newborn health in the United States is on a steep decline, especially in under-resourced communities, leaving vulnerable women and babies behind. Shockingly, the U.S. ranks 55th globally in maternal mortality, with rates soaring to 32.9 per 100,000 live births—doubling in the past two decades. Even more concerning, Hispanic and Alaska Native women face mortality rates twice that of white women, while Black women suffer three times as much risk.
While we should do better across all segments of society, communities of color suffer extreme disparities in adverse pregnancy events: preterm birth, gestational diabetes, preeclampsia, and life-threatening hemorrhage. Stress, especially chronic stress, is deeply implicated in these inequities.
The Galas Project Overview
Introducing The Galas Project, a groundbreaking initiative envisioned by and built upon the scientific work of PNRI’s former Principal Investigator, David J. Galas, PhD. David was one of the leaders of the Human Genome Project and a renowned scientist in the fields of human genetics, molecular biology, computational biology, and physics. This project combines genetics with his novel machine learning technologies to improve big data analytics.
The current initiative is being planned and designed by PNRI’s Senior Investigator Lisa Stubbs, PhD, and David’s former collaborator, focuses on understanding the interplay between stress and genetics to affect pregnancy outcomes, particularly among women who are underrepresented in research. From gestational diabetes (GDM) to preterm birth, this research is pivotal to uncovering disparities and identifying solutions.
Research Objectives and New Initial Finding
This research is planning to work at the leading edge of genetic research to develop new diagnostics, treatments, and prevention to improve health and reduce these health disparities and their social and economic impacts. We are delving into the world of pregnancy complications and chronic stress indicators within a diverse sample of Black women from an under-resourced community in Louisiana.
Our initial results from our pilot Decoding Stress Project identified a novel genetic factor that may shield some Black women from gestational diabetes; this novel gene is the first to be identified as relevant to GDM in the Black community. Its discovery highlights the potential for more inclusive personalized risk assessment and prevention.
Project Framework and Goals
Clinical Outreach: The Galas Project will begin with a network of partnering physicians and their patients in underserved urban and rural communities. All these patients are living under similar, stressful life conditions, and although many go on to have successful, uneventful pregnancies, the risk of pregnancy complications is particularly high. We will focus on clinics in the Precia Group network, led by Donna Russell. Precia, which specializes in women’s health research, will oversee the development of clinical protocols, and manage the secure collection, maintenance, documentation, and preparation of biological samples needed by the PNRI scientific team.
Goal 1: Develop genetic profiles, or genotypes, from the maternal blood samples, including women with pregnancy complications and normal pregnancy “controls.” As genetic profiles are developed, PNRI scientists will use computational and novel statistical methods to identify genetic markers that are more prevalent (susceptibility factors) or less prevalent (protective factors) in the women with complicated pregnancies. These genetic studies will allow us to identify variant genes that render certain mothers especially susceptible, and others especially resilient, to certain types of pregnancy complications. Once validated by further computational and experimental analysis, these new markers can be used in clinics to test women early in pregnancy to identify those who need to be specially monitored and preemptively treated before complications can begin.
Goal 2: Validate the candidate genes and investigate their biological functions, seeking to understand how the variant genes render their endangering or protective effects on prospective mothers. This understanding is the first step toward developing personalized treatments to prevent or mitigate the negative effects of pregnancy complications in a clinical setting. To validate the genes experimentally, PNRI scientists will carry out two kinds of focused analysis.
First, in addition to maternal blood, Precia plans to oversee the collection of placenta samples from selected patients and controls. Placental insufficiency is a major cause of pregnancy complications, and this vital tissue holds many important clues. PNRI’s Stubbs and McLaughlin Labs will work together to analyze tissue and cellular structure and the molecular features of the placental tissue and will use these clues to identify the biological pathways that have been disturbed in these pregnancies.
Second, we will develop cell-based and mouse-genetic models to investigate the functions of the novel candidate genes, validating their role in pregnancy complications and discovering how variation in those genes leads to stress-induced complications. Similar studies are underway at PNRI to investigate already-validated susceptibility genes; we will develop similar models to investigate new candidate genes. This analysis will develop the information to take these novel genes back to the clinics, where they can identify susceptible and resilient women early in pregnancy for personalized treatment.
Goal 3: Analyze the genetics of children from complicated pregnancies as well as their mothers, using cord blood collected at birth. Complicated pregnancies are dangerous for mothers and babies before and at birth. But even when babies are successfully delivered, both children and mothers in complicated pregnancies are left with a lifetime legacy of increased risk, developing physical and mental health disorders at markedly higher rates than other individuals. Our long-term goal will be to identify markers that contribute to these pernicious health issues, to identify the vulnerable mothers and children and improve the quality of their lives. Like the maternal factors, genetic factors identified in children will be validated computationally and tested experimentally at PNRI.
We are in the thrilling exploratory phase of planning this ambitious project to validate and expand upon the groundbreaking results from the pilot project. Join us in revolutionizing maternal and newborn healthcare, as The Galas Project strives not only to bridge racial gaps in health outcomes but also to pave the way for enhanced care for all women.