Nuclear epidermal growth factor receptor (EGFR) signaling network in the heart

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The proposed research investigates new signal pathways in the heart.  Specifically, we will study the Epidermal Growth Factor Receptor.  The EGFR is a protein that plays an important role in normal development, growth, mechanical sensing, and signaling pathways in the heart.  The novel aspect of our research is that we will be studying the EGFR in the nucleus of heart muscle cells.  The nucleus is the cell compartment which contains chromosomes.  Using a combination of sophisticated microscopy and biochemical assays, we will first confirm that the EGFR does localize to the nucleus of heart muscle cells.  Second, because the EGFR participates in heart development and growth, we will examine the effect of growth stimuli such as stretch or hormones on the activity of the EGFR.    We will then focus our attention on how the EGFR moves from the cell membrane to the nucleus.  The experiments that we have designed will determine how the EGFR is internalized into the cell, and whether other proteins help to shuttle the EGFR through the cell to the nucleus.  Finally, since the nucleus is the cell organelle in which genes are expressed, we will determine whether EGFR found in the nucleus of heart cells influences gene expression.Our research will advance our understanding of how signals are transmitted in the nucleus of heart muscle cells, which represents a new and exciting mechanism by which gene expression in the heart might be regulated.