Massachusetts General Hospital

Research Investigator Profile

Jack T. Rogers, PhD

• Associate Professor of Psychiatry
  Harvard Medical School

Research Description

Dr. Rogers’ laboratory studies iron metabolism and how it impacts on disease process such as anemia and Alzheimer's disease. His scientific focus has been to study the translational regulation of the mRNAs for the Alzheimer's Amyloid Precursor Protein (APP) and the subunits of the iron storage protein ferritin.

Currently his research is directed toward understanding how RNA structure controls APP-mRNA translational regulation relevant to neurodegenerative diseases including Alzheimer's disease and Down's syndrome. The APP-mRNA 5'UTR mediates increased APP synthesis and amyloid peptide secretion from astrocytes in response to inflammation. Genetic approaches are being used to explain how the 5' untranslated region (5'UTR) of APP mRNA operates as a translational control element in neuronal and astrocytic cells. In collaboration with Message Pharmaceuticals, his laboratory have developed a project to use small RNA-binding drugs to suppress APP-mRNA translation from the 5'UTR stem-loop, and thereby develop new therapeutic strategies to inhibit A Beta-peptide secretion and amyloid plaque build-up.

Iron chelation also controls APP gene expression at the translational level. Dr. Rogers’ laboratory recently discovered the existence of an Iron-regulatory domains in the APP-mRNA 5'UTR. This result led to investigations on how iron metabolism might be important for the function of APP. To follow-up on this finding, his laboratory is examining whether APP over-expression enhances iron uptake into cultured cells and whether secreted APP is a copper-dependent ferroxidase.

Dr. Rogers has several ongoing collaborative projects including examining whether iron and inflammation regulate ferritin gene expression and translation in liver cells (Dr. K Bridges, Brigham and Women's Hospital Boston) and how thyroid hormone and Thyroid-Releasing Hormone cooperatively increase ferritin gene expression in Pituitary cells (Dr. P. Leedman Univ. Perth Western Australia).