The back-and-forth between the laboratory bench and the clinics informs some of our most valuable research opportunities. Clinical observations and challenges at the bedside are taken to the lab to develop solutions that are brought back to patients, aiming to improve health outcomes. To illustrate this concept, I would like to highlight the genetics and genomics research being conducted by Carlos Prada, MD, Division Head of Genetics, Genomics, and Metabolism; Erica Davis, PhD, Principal Investigator for the Advanced Center for Translational and Genetic Medicine Laboratory; and Aaron Hamvas, MD, Division Head of Neonatology. Their investigation into the genetic origins of diseases observed in newborns and children with genetic diseases offers valuable insights into therapeutic approaches that can enhance patient care.
Most patients with neurofibromatosis type 1, a common genetic condition affecting about 1 in 3,000 newborns, develop plexiform neurofibromas, benign tumors that grow along the nerves in various parts of the body. These tumors can cause pain and disfigurement and impact body functions such as mobility, breathing, and swallowing. As the principal investigator for National Institutes of Health-funded research aimed at identifying biomarkers for plexiform neurofibromas in patients with neurofibromatosis type 1, Carlos seeks to understand tumor formation and growth better and pinpoint patients at higher risk of developing complications. While there is currently no cure for neurofibromatosis type 1, there are two therapies approved for the management of symptomatic plexiform neurofibromas. Identifying biomarkers that indicate the early development of neurofibromas can expedite patients’ access to these therapies, helping to slow the progression of their disease. He hopes that the results of this study will inform his future work on improving therapeutic interventions. Along with Erica, Carlos co-leads a team of Lurie Children’s clinicians and scientists participating in the Undiagnosed Diseases Network. In this NIH initiative, teams of experts at multiple clinical sites around the United States conduct genetic research to provide answers to patients. Inconclusive clinical diagnoses lead to stress for the families worried about their children’s development, quality of life, and overall prognosis. Still, as Carlos explains, the team’s research will increase the number of diagnoses, particularly for patients with rare genetic conditions, providing researchers with information that may lead to therapeutic interventions or clinical trial opportunities.
Erica leads a team whose basic science research identifies genes that cause neurodevelopmental disorders and ciliopathies, where disruptions in the microscopic hair-like structures on cells called cilia dysfunction contribute to defects in brain development, facial formation, and essential cellular signaling pathways. Her team generates new insights about the genetic mechanisms underlying these diseases. Their discoveries regarding disease mechanisms are made through cell-based and animal (primarily zebrafish) models, which help identify potential therapeutic targets. These findings also inform the work of clinical trials and other researchers in basic and preclinical science, such as Carlos and Aaron. Additionally, as part of her collaborations with Carlos, Aaron, and scientists from other institutions, Erica enrolls participant families in research after they have received inconclusive clinical genetic test results. Her team then re-analyzes genomic data to search for previously unidentified causes of disease. While Erica is excited about discovering new biology through genomic research, mentoring the next generation of geneticists, and collaborating with experts worldwide, her most meaningful work is providing essential information to the families of children with rare genetic diseases.
Throughout his career, Aaron’s research into the roles of genes in the development of lung diseases has generated discoveries that have had long-lasting positive impacts on patients’ health outcomes. He recalls one patient he had the honor of caring for early in his career—a newborn with severe respiratory failure who had a sibling who passed away from the same condition—and how he and his colleagues identified a genetic cause of the respiratory failure. These findings, Aaron explains, enabled clinicians to detect new genetic disorders and identify these patients as potential candidates for lung transplantation, some of whom are alive and thriving years after receiving transplants. Since then, the accelerated pace of advancements in genetic technologies, including whole genome sequencing, single-cell sequencing, gene editing, and emerging artificial intelligence platforms, have created more opportunities for discoveries. For his latest NIH-funded study, Aaron’s team will use computational approaches to analyze patients’ clinical and genetic data to identify mechanistic pathways that influence cardiorespiratory outcomes of prematurity, with the goal that this information may one day lead to earlier and more specific treatments for lung diseases that result from prematurity.
The genetics and genomics research led by Carlos, Erica, and Aaron continues to profoundly impact the health and well-being of children with genetic diseases and illustrates our role as experts in this area. By recognizing clinical challenges in patients and then studying them in the laboratory and clinical trials setting, Carlos, Erica, and Aaron produce findings that substantially improve patient care.
