Our basic science researchers build upon our highly successful clinical care programs and linkages with other researchers throughout the School of Medicine and Duke University to make fundamental discoveries that will help diagnose, treat and prevent illnesses impacting the health and well being of children. Their laboratories also serve as sites for the training of tomorrow's clinician-scientists and academic leaders who will innovate and discover new ways of caring for children.
As a neonatologist, my research interests revolve around improving the survival and quality of life of high-risk neonates cared for in Neonatal Intensive Care Units. My primary interest is perinatal brain injuries impacting both full-term infants and those born prematurely. One of the most common forms of perinatal brain injury involves damage to white matter (myelin). My laboratory has developed models of perinatal brain injury to investigate how the endogenous neural stem cell responds to myelin injury.
Our research involves identifying gene regulatory elements across the genome to help us understand how chromatin structure dictates cell function and fate. For the last 25 years, mapping DNase I hypersensitive sites has been the gold standard method to identify the location of active regulatory elements, including promoters, enhancers, silencers, and locus control regions. We have developed two technologies that can identify most DNase I hypersensitive sites from potentially any cell type from any species with a sequenced genome. These data can be combined with other wet-lab and computational data types to better understand how these regulatory regions control global gene expression.
Dr. Deel is a clinician scientist in Pediatric Hematology/Oncology. In addition to caring for pediatric patients with hematologic disorders or malignancy, his research focuses on finding novel ways to target fusion-positive pediatric sarcomas. His current work focuses on understanding the gene regulation and molecular pathways responsible for alveolar rhabdomyosarcoma, which is among the most difficult to cure pediatric cancers.
Our laboratory focuses on the control of breathing and pulmonary mechanics in murine models of several genetic diseases. We are currently focuased on ALS mouse models and the Pompe disease mouse model. We examine the impact of gene therapy and neuromodulation on respiratory insufficiency that results from neuromuscular weakness. As a clinician scientist, my goal is to bring therapy from the bench to the bedside and enhance our research at the bench through observations at the bedside.
Dr. Gbadegesin's research is focused on understanding the critical pathways that are involved in the pathogenesis of nephrotic syndrome and in congenital malformations of the kidney and the urinary tract. He and his group have established a phenotypic and biorepository data base for more than 600 children with hereditary and sporadic nephrotic syndrome. In the past two years they have identified two novel genes for hereditary nephrotic syndrome and vesicoureteric reflux (VUR). They have also identified a disease risk allele for childhood onset steroid sensitive nephrotic syndrome (SSNS).
A multidisciplinary approach to care of individuals with genetic disorders in conjunction with clinical and bench research that contributes to:
1) An understanding of the natural history and delineation of long term complications of genetic disorders
2) The development of new therapies for genetic disorders through translational research
3) The development and execution of large multicenter trials to confirm safety and efficacy of potential therapies
4) Role of antibodies/immune response in patients on therapeutic proteins.
The focus of our research has been the development of gene therapy with adeno-associated virus (AAV) vectors, most recently by genome editing with CRISPR/Cas9. We have developed gene therapy for inherited disorders of metabolism, especially glycogen storage disease (GSD) and phenylketonuria (PKU).
Dr. Kurtzberg conducts both clinical and laboratory-based translational research efforts, all involving various aspects of normal and malignant hematopoiesis. In the laboratory, her early work focused on studies determining the mechanisms that regulate the choice between the various pathways of differentiation available to the pluripotent hematopoietic stem cell.
I am interested in the genetic and molecular mechanisms of sudden cardiac arrest in children. I am a physician-scientist trained at the confluence of pediatric cardiology, clinical electrophysiology, human genetics, and molecular biology which I apply towards the care for children with heritable arrhythmic disease of the heart. I run a basic science research lab exploring the genetic and molecular causes of sudden cardiac death in children and young adults.
Sarcomas are among the most difficult-to-treat cancers in pediatric oncology, with metastatic forms having the highest mortality. We have established genetically defined human cell-based models and genetically engineered murine models for the pediatric skeletal muscle cancer known as rhabdomyosarcoma. Using these models, we can study the causative role of certain genetic changes (e.g. chromosomal translocations and oncogenic RAS) in rhabdomyosarcoma formation and treatment resistance.
Dr. Mikati’s clinical research has centered on characterization and therapy of pediatric epilepsy and neurology syndromes, describing several new pediatric neurological entities with two carrying his name (POSSUM syndromes # 3708 and 4468), developing novel therapeutic strategies for epilepsy and related disorders particularly Alternating Hemiplegia of Childhood, and applying cutting edge genetic and Magnetic Resonance Imaging techniques to drug resistant pediatric epilepsy.
The primary focus of the laboratory is the study of humoral responses to vaccination and infection with the goal of understanding how to elicit protective responses by vaccination. The laboratory develops antigen-specific reagents for the quantitation and isolation of B cells, and has active projects to study HIV-1, influenza, syphilis, and autoimmunity.
Our laboratory focuses on studying the molecular pathogenesis of Aspergillus fumigatus. All of our research is translational in nature and performed with the specific goal of directly improving our fundamental understanding of how and why this organism is so deadly and how to best prevent, diagnose, and treat it. Our laboratory uses a wide variety of molecular genetics tools to delete or mutagenize pathogenesis genes and proteins and subsequently analyze their function and role in disease, including numerous genomic, proteomic,and biochemical approaches.
My research innovatively integrates gnotobiotic murine models, immunology, microbiology, and characterization of the microbiota with the ultimate aim of identifying specific commensal bacteria with immunomodulatory potential and subsequent characterization of their biologic effects. We have recently developed an inventive approach for identifying with high specificity organisms within the microbiota that are causally related to the phenotype of interest.
I am a pediatric oncologist with a clinical and research focus on the care of adolescents and young adults with sarcoma. I have led multiple institutional and national clinical trials exploring new therapies for patients with recurrent sarcoma, and am interested in new drug development and identification of predictive biomarkers.
The immune system protects the host from microbial infection but can cause diseases if not properly controlled. My lab is interested in the receptor signaling mediated regulation of immune cell development and function as well as the pathogenesis and treatment of autoimmune diseases and allergies. We are currently investigating the roles diacylglycerol kinases (DGKs) and TSC1/2-mTOR play in the immune system.