Basic & Translational Research Basic & Translational Research at Connecticut Children’s brings investigators together to participate in collaborative, interdisciplinary research environment to study health outcomes and pursue breakthrough treatments. The Center promotes research that combines basic science with clinical expertise to facilitate next-generation treatments for pediatric lung disease and digestive disorders, among others. Our scientists and clinicians work hand-in-hand to pursue innovative treatment models and research. COVID-19 Led by Dr. Juan C. Salazar, in collaboration with Dr. Michael Lynes (UConn Storrs) and Dr. David Lawrence (New York Department of Health), the Identifying biomarker signatures of prognostic value for Multisystem Inflammatory Syndrome in Children (MIS-C) study is one of only eight studies funded under the NIH’s PreVAIL kIds program. The study aims to develop a tool to diagnose MIS-C in children, a serious complication of COVID-19. In addition, the new diagnostic tool will help differentiate MIS-C from Kawasaki disease, a serious vasculitis that also affects children. Clinicians from four hospitals in the U.S. and Colombia, led by Dr. Alex Hogan at Connecticut Children’s and Dr. Eduardo Lopez in Cali, Colombia, are currently enrolling and collecting patient health information along with blood and saliva. With support from Kathy Herbst and her research team in Connecticut, participants are followed for four years to document long-term outcomes. Scientists at laboratories across Connecticut and New York, are analyzing the blood and saliva to identify biomarkers in order to develop a diagnostic test for MIS-C. Additionally, analysis of biomarkers and patient characteristics will contribute to a better understand why some children develop MIS-C or become seriously ill, and others do not. Led by Drs. William Zempsky and Juan C. Salazar, Connecticut Children’s is participating in an important national study, A Multi-Center Observational Study: The RECOVER Post Acute Sequelae of SARS-CoV-2 (PASC) Pediatric Cohort Study. The study, funded under the NIH RECOVER Initiative, is a national effort that brings together scientists, clinicians, patients, and caregivers to take on a critical problem: recovery from the long-term effects of COVID-19. The Connecticut Children’s research team is collecting data that will be integral to further the understanding and treatment of long-term complications associated with COVID-19. Regenerative Medicine Led by Dr. Christine Finck with an emphasis on regenerative technology, researchers are leading the way in Regenerative Medicine. Utilizing a patient’s own cells to reduce rejection responses, Dr. Finck and her researchers are focusing on pediatric and neonatal diseases that arise from congenital defects, preterm birth, accidental injuries, and cancer. The Regenerative Medicine research team, using patient-specific stem cell populations and de-cellularized lung scaffolds, have investigated pediatric lung diseases for their causes and potential treatments. This research has expanded into esophageal defects, the use of synthetic polymers and scaffolding as a therapeutic option, and advanced technology for creating in vitro and in vivo 3D bioprinted scaffolds. Dr. Finck and her team use novel 3D bioprinters to create scaffolds that are designed specifically for the host and are technologically reproducible, exploring the next frontier of regenerative science. The laboratory of Dr. Courtney Rowe focuses on improving postoperative outcomes for pediatric urologic patients. A primary focus is on optimizing urethral healing using regenerative medicine techniques. Urethral surgery is performed for a number of conditions, from hypospadias, the second most common congenital difference in boys, to urethral strictures suffered after blunt trauma in adults. Complications after surgery are high, in part due to poor understanding of urethral healing. The Rowe lab seeks to improve outcomes using in vitro models that will ultimately translate into interventions that support urethral healing. Rare Diseases Dr. Emily Germain-Lee has an extensive clinical and basic science research program focused on finding new therapies and improving the quality of life for patients with rare bone disorders. A major focus of her clinical and translational research has been Albright hereditary osteodystrophy (AHO), a condition caused by mutations in a gene that is crucial to hormonal regulation and skeletal development. Dr. Germain-Lee has clinically evaluated the largest population of patients with this disorder worldwide. By combining clinical research with basic science investigations, she has been able to gain new insights into the AHO phenotype and disease pathogenesis. One of her major contributions was demonstrating that patients with this condition often have evidence of growth hormone (GH) deficiency due to growth hormone-releasing hormone (GHRH) resistance. This finding changed the standard of care for these patients to include GH testing and was part of two FDA R01 clinical trials examining the outcome and potential benefits of GH treatment in this population. Dr. Germain-Lee also has a translational research program aimed towards finding new treatments for osteogenesis imperfecta (OI, also referred to as brittle bone disease). Based on clinical features in OI of diminished muscle mass secondary to the immobilization that typically accompanies this disorder, Dr. Germain-Lee went on to show that blocking the activin/myostatin signaling pathway in a mouse model of OI can lead to increases in bone and muscle mass. This raised the possibility that drugs targeting this pathway may be a new therapeutic strategy for patients with OI. In fact, this potential treatment strategy is applicable to patients with loss of bone and muscle due to chronic illness of any etiology, including aging. Given that microgravity mimics immobilization with loss of both bone and muscle, Dr. Germain-Lee’s recent investigations with her colleagues surrounding mice that they sent to the International Space Station revealed that this therapeutic strategy led to improvements in both bone and muscle mass in the setting of microgravity. This has implications for treatments to combat the muscle and bone loss occurring concomitantly not only in people afflicted with disuse atrophy on Earth but also in astronauts in space. Neonatal Microbiome Led by Dr. Adam Matson, studies on the microbiome are focused on determining the influence of bacterial populations and/or their products on neonatal outcomes and intestinal health in premature infants. His multidisciplinary team integrates state-of-the-art microbial sequencing technology and translational research approaches to track specific pathogens in the neonatal intensive care unit and to characterize metabolic factors that contribute to necrotizing enterocolitis, a catastrophic intestinal disease of prematurity. This research includes the establishment of a Neonatal Specimen Biorepository, allowing several additional research projects ranging from the influence of gut microbes on neurodevelopment to their impact on liver function. In a complementary fashion, Connecticut Children’s Human Milk Research Center is working to better understand the origin of bacterial populations in milk and how they influence establishment of the infant gut microbiota. Pediatric Oncology Dr. Ching Lau is a pediatric hematologist oncologist at Connecticut Children’s and conducts research on the development of personalized medicine approaches in pediatric oncology. The Lau Lab uses the powerful combination of genomic technologies, together with mouse modeling, to understand changes in gene expression that underlie various types of pediatric cancers. Based on this information they identify and validate biomarkers that could be used clinically to predict response to therapy and outcomes. In addition, some of these genetic changes are also tested as potential therapeutic targets and when validated, will ultimately lead to clinical trials.