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Gregory A. Grabowski, MDProfessor; Director of Division of Human Genetics Department of Pediatrics; Division of Human Genetics
Dr. Grabowski investigates the pathogenesis of lysosomal storage diseases, such as hepatopathies secondary to acid-lipase deficiency (cholesteryl-ester storage disease, Wolman’s disease). Studies range from gene transfer, purification and characterization of recombinant selectively mutated enzymes, knock-in and knock-out mouse generation, and genome wide studies of transcriptomes and proteomes. These studies use high-density microarrays and bioinformatics to identify molecular signatures of lysosome-based biological processes, and integrative morphology to define the cellular basis of molecular signatures and the phenotype of organs of the digestive system in gene-targeted mice. The overall goal of his research program is to define the nature of the signature pathways in disease pathogenesis, and the evolution of the disease phenotypes in mouse models that have been developed as prototypes for selected human diseases. By combining biochemistry/molecular genetics, high-throughput functional genomics, and histopathologic approaches, new strategies will be developed for effective therapeutic interventions and their evaluation by novel biomarkers. Particular emphasis relates to the molecular signals used by macrophages to control the tissue-specific injury of the liver and intestine.
Dr. Grabowski collaborates with Dr. Aronow to identify the signature pathways in the pathogenesis of a mouse model of Gaucher Disease. He also works with Dr. Witte and uses the Integrative Morphology Core examining the supplementation of lysosomal acid lipase in animal models. Projection of Core use: Gene and Protein Expression, Bioinformatics, and Integrative Morphology Cores.
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