Overview
Clinical and basic research activities are directed to interventional genetics and the genetic/molecular basis of disease. Through the Cincinnati Children's Lysosomal Disease Center, a major focus of clinical research is to improve the health of individuals with inborn errors of metabolism (lysosomal disorders as well as fatty acid and protein metabolic disorders) through development and evaluation of new drugs. In a program spearheaded by Dr. Grabowski, new advances in the treatment of bone involvement in Gaucher disease are being sought. Drs. Grabowski, Hopkin, and Leslie head programs for the development and evaluation of new treatments and therapies of Gaucher, Fabry, Pompe, Mucopolysaccharidosis type I (Hurler syndrome), and Niemann-Pick B diseases. As a critical component for this clinical research, an active enrollment of patients with these rare diseases into large collaborative international registries is ongoing. Dr. Bao continues international studies of mutagenic agents in cancer, with specific focus on dioxin, an industrial and environmental toxin. Dr. Schorry is an integral part of clinical studies in neurofibromatosis (NF), including the natural history of bone complications, learning and behavioral problems in patients with NF1, and drug trials for plexiform neurofibromas and other NF-related tumors. Dr. Smolarek leads studies to assess, optimize and implement state-of-the art cytogenetics analyses, such as comparative genomic hybridization (CGH) and recent implementation of an expanded SNP microarray to detect cytogenetic imbalances that are smaller than what can be detected through routine chromosome analysis. Dr. Tinkle studies the natural history of connective tissue disorders such as Ehlers-Danlos and Marfan syndromes to better characterize the disease process.
Basic research focuses on the genetic/molecular basis and treatment of complex human diseases. Research in Dr. Du’s laboratory uses mouse models to understand the molecular pathophysiology and therapeutic potential of replacement therapy for the inherited lipid metabolic disorders, Wolman disease and cholesteryl ester storage disease. Dr. Grabowski, Dr. Sun, and Dr. Xu seek to identify the shared proinflammatory signature pathways in the pathogenesis and propagation of sphingolipid disorders and, using mouse models, the molecular and genetic therapies of Gaucher disease and saposin deficiencies. Dr. Guan has identified and continues to characterize significant modifier genes in mitochondrial function and their role in disease susceptibility, particularly deafness. Dr. Neilson studies the genetic contributions to acute necrotizing encephalopathy (ANE), a disorder in which children are predisposed to a devastating neurologic injury following common infections. Research in the lab of Dr. Nichols seeks to identify genetic variants contributing to susceptibility to pulmonary arterial hypertension, Parkinson disease, and juvenile idiopathic arthritis. Using quantitative trait locus analysis, Dr. Prows identified regions containing genes predisposing to acute lung toxicity induced by oxidants such as hyperoxia and ozone, and is seeking modifier genes that affect the severity of RSV infection or interstitial lung disease. Dr.Qi performs basic research focused on the role of saposin C in multivesicular body formation and neuropathogenesis; and translational research to develop saposin C-containing nanovesicles as a novel anticancer agent.
As a key component of the overall research goals, Mr. Keddache manages the Genetic Variation and Gene Discovery Core, which provides high-tech genetic sequencing and genotyping services for CCHMC, UC, and the national/international community. In addition to managing the Molecular Diagnostics Laboratory, Dr. Zhang performs clinical and translational research on the genetic etiology of primary immunodeficiencies, such as HLH, XLP and ALPS, and participates in a multi-disciplinary team (Genetic Pharmacology Service) to advance personal and preventive medicine.
