Grants Awarded

Comprehensive mRNA/miRNAs Expression Analysis in Familial Hemophagocytic Lymphohistiocytosis Type 2, Using the C57BL/6-Prf1tm1Sdz/J Murine Model

Principal Investigator
Janos Sumegi, MD, DSc, PhD
Cincinnati Children’s Hospital Medical Center, Cincinnati, OH USA

Date of Award
December 2014

Amount of Award

Layperson Summary
This project addresses several issues of central importance of hemophagocytic lymphohistiocytosis a rare (1 per million person), life threatening “immunodeficiency condition” with severe hyperinflammation and hemophagocytosis caused byuncontrolled proliferation of activated blood cells,secreting high amounts of inflammatory cytokines. The hemophagocytic lymphohistiocytosis represent an increasingly complex group of genetically diverse conditions with considerable diagnostic and therapeutic difficulties. In order to make use of basic research findings in the efforts to progress towards new clinical therapeutic approaches, animal models are imperative precursors for translational studies. We propose topursue a genome-wide gene expression analysis using the murine model of the human hemophagocytic lymphohistiocytosis to evaluate phenotype associations with spatial and temporal changes in the course of the disease and validate the murine data in human subjects. A broad comparison will be made between mouse phenotype and human FHL2 on the basis of global gene expression patterns, and biochemical pathways. Identification of gene expression signatures consisting of multiple genes are anticipated to specify targeted intervention and predict responsiveness to targeted therapies, and could ultimately improve the ability of clinicians to provide optimal treatment for their patients.