| The significance of proteins in biological processes has driven increasing numbers of studies focusing on proteomics in various biological systems during the past decade. These studies include: profiling proteins in simple or complex samples, investigating protein-protein interactions, characterizing post-translational modifications of proteins, and analyzing expression level of proteins in different biological or disease states. Such studies can provide valuable information to decipher the roles of proteins in numerous of biological processes and advance our understanding of mechanisms of various diseases. Mass spectrometry (MS), with its ability of parallel analysis of thousands of proteins, has become the standard technology to investigate proteome in recent years. In my dissertation research, I have employed MS-based tools to investigate differential proteomic events in various biological systems. The applications include: revealing the interacting proteins of MBD1 (chapter 3), characterizing phosphorylation of GATA-2 (chapter 4) and hydroxylation of alpha1 (V) collagen chain (chapter 6), and profiling secretome of vascular smooth muscle cells (VSMCs) in response to TGF-beta/Smad3 stimulation (chapter 5). Results presented here have provided insights into: 1) the function of MBD1 in neural development; 2) the mechanism of GATA-2 in regulating hematopoiesis; 3) the role of Smad3-dependent TGF-beta signaling in the atherosclerotic process; and 4) the unique biological properties of alpha1 (V) collagen chain to induce the autoimmunity in lung transplantation. Collectively, this thesis research has developed improved proteomics methodology, showcased the power of MS-based tools, and enabled biological discovery in several important processes of biomedical and clinical relevance. |
