Daniel R Schoenberg, PhD, Affiliate
College of Medicine
Molecular & Cellular Biochemistry / Molecular and Cellular Biochemistry
Molecular Biology and Cancer Genetics
Sequence Deletion, Carcinoma, Papillary, Thyroid Neoplasms, Leukemia, Erythroblastic, Acute
The Schoenberg lab is nationally recognized for discoveries in fundamental mechanisms of post-transcriptional gene regulation and the application of this knowledge to signal transduction, cancer and inherited diseases. The four projects currently under study look at the molecular mechanisms of endonuclease-mediated mRNA decay, mRNA decay in beta-thalassemia, cytoplasmic capping and ribozyme inactivation of microRNAs. Endonuclease catalyzed mRNA decay is a minor pathway that acts on specific sets of mRNAs. It is linked to cancer through activation of this process by the c-Src tyrosine kinase and recent work showing activation of this decay process stimulates cellular motility. The second project studies the molecular basis for beta-thalassemia (Cooley’s anemia), the most prevalent inherited disease throughout the world. This is caused by inheritance of two copies of beta-globin genes with a premature termination codon, which in turn activates endonuclease cleavage of the defective mRNA. The basic science here is to lay the groundwork for developing rational drug treatments for this disease. The third project looks at the question how mRNAs that are silenced, for example by microRNAs, can be reactivated and returned to the translating pool. We identified a population of capping enzyme in the cytoplasm and a pool of uncapped mRNAs that appear to be re-capped by this enzyme. In addition this enzyme likely catalyzes the capping of a new family of small RNAs. The final project is a collaboration with the Gopalan lab at Ohio State that seeks to develop RNase P-based ribozymes as tools for targeted microRNA degradation. The focus is on miR-122, the most abundant microRNA in liver, which is involved in cholesterol metabolism, the replication of hepatitis C virus, and hepatocellular carcinoma.