I was trained in a wide variety of technologies as a protein biochemist in graduate school, which served as the foundation of my postdoctoral work on identifying extracellular signals that induce transformation events in early heart morphogenesis. By using complementary protein and molecular approaches we were able to identify trace levels of an extracellular aggregate of proteins, what are now known to be secretory vesicles termed “exosomes”, that induce the formation of valvuloseptal precursors in the embryonic heart. As part of an NIH funded Cardiovascular Proteomics Center our group developed novel technologies for characterizing dynamics of the embryonic heart proteome. This allowed us to use a platform of methodologies with complementary strengths, e.g., 2D difference-in-gel electrophoresis (DIGE) and the MS-MS based method of isobaric tag for relative and absolute quantitation (iTRAQ) to compare posttranslational modifications and differential composition of protein extracts, and MALDI-TOF imaging of tissue sections to discover spatial changes in protein distribution. We also developed a bioinformatics tool for staging embryonic hearts based on their MALDI-TOF profiles via a Random Forest algorithm. Current projects involve using these approaches to assess subtle changes in the proteome that precede overt morphological defects in the developing heart and cochlea in response to potential teratogens, gene knockout models and aging.