We continue our efforts to enhance the clinical, teaching, and research goals involving individuals and their families afflicted with heritable disorders. Clinically, the numbers of patients evaluated and provided care continues to expand. In addition, innovative programs to provide genetic care to underserved populations in the Cincinnati Region as well outreach programs continue to be successful. These programs complement our expanding outreach programs in the Cincinnati Region and at the Toledo Children's Hospital. The laboratory services including Cytogenetics, Molecular, and Metabolic Diagnostic Laboratories have continued to grow rapidly and serve Cincinnati Children's, UC, the Cincinnati area and the State of Ohio. Concomitant with these programs has been an expansion of clinical activities in Medical Genetics at Cincinnati Children's and UC.
The educational and service programs continue to grow and include in the Genetic Counseling Program, the Nurse Genetic Program (Distance learning), the Genetic Fellowships, and the Medical Genetics Residency Program. The Distance Learning programs include two web and interactive modules and a set of 14 curriculum modules (C. Prows). The genetic counseling program has placed emphasis on minority recruitment (N. Warren). A unique collaborative service, the pharmacogenetics service (GPS) has integrated genetic variation in drug metabolizing enzymes with clinical care and therapeutic outcome. Working collaboratively, Drs. Wenstrup (Division and Program for Human Genetics), Glauser (Neurology), Vinks (Clinical Trials) and Nick (Epidemiology and Biostatistics) with Bioinformatics have developed accessible and generalizable systems for individualization of drug dosing based on an individual's genetic constitution.
Clinical and basic research activities are directed to interventional genetics and the genetic/molecular bases of disease. Clinical research focused on expansion of therapeutic approaches through the Cincinnati Children's Lysosomal Disease Center, including new enzyme and adjunctive therapies. For Gaucher disease, the program spearheaded by Dr. Wenstrup, should provide major new advances in the treatment of bone involvement in this disease. Drs. Hopkin, Leslie, and Grabowski have headed programs for therapy of Gaucher, Fabry, Pompe, Mucopolysaccharidosis type I (Hurler syndrome), and Niemann-Pick B diseases using enzyme therapy and/or bone marrow transplantation, and contributions to large scale international databases for these diseases. Dr. Bao continues international studies of mutagenic agents in cancer. Dr. Schorry is an integral part of studies of bone disease and therapeutics for large Neurofibromatosis-1 populations
Basic research has focused on the genetic/molecular basis and treatment of human diseases. 1) Identification of significant modifier genes of mitochondrial gene function and their role in disease susceptibility, particularly deafness (Guan). 2) Critical role of collagen type V in the initiation of collagen formation using novel mouse models (Wenstrup). 3) Identification of novel genetic variations in selected genes as contributing to Parkinson's disease, pulmonary hypertension, spheroid body myopathy and good health (Nichols). 4) Development of ribozymes as specific therapeutic agents in unique prototype mouse models (Wenstrup). 5) Localization of genes predisposing to lung toxicity by hyperoxia and linkage studies for hypertrophic myocardiopathy (Prows). 5) The use of small lysosomal proteins, saposins, as antineoplastic agents based on their structural organizations (Qi). 6) identification of shared proinflammatory signature pathways in the pathogenesis and propagation of sphingolipid disorders, and molecular and genetic therapies using mouse models of Gaucher disease and saposin deficiencies (Grabowski, Sun, Xu). 7) Characterization of acid lipase's role in the pathogenesis of emphysema mediated by PPAR_ (Du). 8) Development of tobacco plant produced human enzymes for clearing of atherosclerotic lesions in pre-clinical mouse models and development of enzyme therapy for Wolman disease/Cholesteryl ester storage disease (Grabowski/Du). The Division and Program for Human Genetics also leads the DNA sequencing and genotyping core for the Computational Medicine Center of Cincinnati Children's and UC (Grabowski and Keddache).
