Director

 
      Dr. Michael L. Paine is the new Director of the Graduate Program in Craniofacial Biology (CBY), a degree program offered by the University of Southern California (USC) Graduate School and administered by the University of Southern California’s School of Dentistry (USCSD). Dr. Paine works at the Center for Craniofacial Molecular Biology (CCMB) at USC. He is the holder of a USC Associates endowed professorial title, being the “USC Associates Professor of Dentistry”. He currently serves at the Vice-Chair of the USCSD Curriculum Committee, and is also an active member of the USC Institutional Review Board (IRB). He also participates as a faculty member in the Graduate “Programs in Biomedical and Biological Sciences (PIBBS)” at USC.

Dr. Paine received his B.Sc. in Biology from Macquarie University in Australia (1985), his Dental Degree (B.D.S.) and Ph.D. from the University of Sydney in Australia (1988 and 1993 respectively), and his Certificate of Periodontology from USCSD (1999).

His current research interests include a better understanding of the structural proteins unique to the developing enamel matrix. These proteins include amelogenin, ameloblastin, enamelin and amelotin. Structural proteins of the enamel matrix manifest specific protein-protein interactions required to produce an extracellular matrix capable of directing the highly ordered structure of the enamel crystallites. Protein-protein interactions must also occur between the secreted enamel proteins and the plasma membrane of the enamel producing cells, the ameloblasts. Such protein-membrane interactions are required to regulate secretion of enamel proteins, to establish short-term order of the forming matrix, to mediate feedback signals to the transcriptional machinery of these cells, and to quickly remove matrix protein debris during amelogenesis. Membrane-bound proteins identified in ameloblasts, and which interact with the structural enamel proteins, include Cd63 (cluster of differentiation 63 antigen) and lysosomal-associated glycoprotein 1 (Lamp1). Both Cd63 and Lamp1 are also integral to the lysosomal membrane, and are thus involved in endocytosis. Recent data suggests that the transport of these two proteins from the cytoplasmic membrane to the lysosomal membrane involves a direct association with the adaptor protein complex AP-3. The long-term goal of his current work is to characterize protein-protein interactions involving the enamel matrix proteins and the plasma membrane proteins of ameloblast cells, and characterize how these interactions influence enamel formation.

A second research project of Dr. Paine relates to pre-mRNA splicing events. Splicing of pre-mRNA occurs in the cell nucleus and is achieved by a multi-protein complex called the spliceosome. Recent proteomic studies indicate that approximately 200-250 proteins comprise the spliceosome, including TFIP11. TFIP11 was discovered in Dr. Malcolm Snead’s laboratory at USC while searching for enamel-specific or tooth-specific proteins. The discovery of TFIP11 was completely unrelated to any connection with pre-mRNA splicing events; this connection was established many years later. Early-unpublished observations did suggest that proper TFIP11 function was essential for cellular survival, with both in vitro and in vivo gene down-regulatory experiments resulting in a lethal phenotype. This observation suggested a very fundamental role for TFIP11 in cellular physiology. TFIP11 also contains a glycine-rich region called a G-patch that is believed to be a RNA-interacting domain. Thus, the second major theme of investigation in Dr. Paine’s laboratory relates to pre-mRNA splicing, and what precise role TFIP11 has in this process.