Roper, Randall J PHD

NARRATIVE The proposed research is relevant to public health because it will create new mouse models that are more like the human Down syndrome condition to identify modifier genes and molecules contributing to the incidence and severity of DS skeletal and cognitive phenotypes, as well as differences between sexes in these phenotypes. This research will provide a foundation to change how the gene-phenotype relationships are deduced in Down syndrome and other syndromic disorders, propose relevant treatments, and ensure that that all children have the chance to achieve their full potential free from disease or disability.

The proposed research is relevant to public health because it will identify genetic, cellular and molecular bases of skeletal phenotypes related to Down syndrome, as well as differences between the sexes in bone development related to Trisomy 21. The projects outlined in this proposal will be done with a team primarily composed of undergraduate students and will strengthen the research environment at IUPUI. The proposed research is relevant to the part of NICHD’s mission to insure that that all children have the chance to achieve their full potential free from disease or disability.

The proposed research is relevant to public health because it uses multi-disciplinary innovative approaches to create new scientific paradigms of trisomic gene expression, and establish improved approaches to translate these therapies from preclinical to clinical trials. Inducible genetic approaches in DS mouse models will target the amplified expression of Dyrk1a during critical periods of brain and bone development in trisomic mice, testing the hypothesis that normalization of trisomic gene expression before—but not after—tissue-specific periods of gene dysregulation will correct cognitive and skeletal deficits. The proposed research is relevant to the part of NICHD’s mission to perform research to insure that that all children have the chance to achieve their full potential for healthy and productive lives, free from disease or disability.