Juan S. Bonifacino, Ph.D.

We investigate the molecular mechanisms by which transmembrane proteins (referred to as cargo) are sorted to different compartments of the endomembrane system in eukaryotic cells. The system consists of an array of membrane-enclosed organelles including the endoplasmic reticulum (ER), the Golgi apparatus, the trans-Golgi network (TGN), endosomes, lysosomes, lysosome-related organelles (LROs) (e.g., melanosomes), and different domains of the plasma membrane in polarized cells (e.g., epithelial cells and neurons). Transport of cargo between these compartments is mediated by carrier vesicles or tubules that bud from a donor compartment, translocate through the cytoplasm, and eventually fuse with an acceptor compartment. Work in our laboratory focuses on the molecular machineries that mediate these processes, including (1) sorting signals and adaptor proteins that select cargo proteins for packaging into the transport carriers, (2) microtubule motors and their cognate adaptor proteins that drive movement of the transport carriers and other organelles through the cytoplasm, and (3) tethering factors that promote fusion of the transport carriers to acceptor compartments. We study these machineries in the context of different intracellular transport pathways, including endocytosis, recycling to the plasma membrane, retrograde transport from endosomes to the TGN, biogenesis of lysosomes and LROs, and polarized sorting in epithelial cells and neurons. We apply knowledge gained from this research to the elucidation of protein trafficking diseases including neurodevelopmental disorders.

Dr. Juan S. Bonifacino received his doctoral degree in biochemistry from the University of Buenos Aires, Argentina, in 1981. He then moved to the NIH, where he pursued postdoctoral studies with Dr. Richard D. Klausner. He rose through the ranks to his current position as Head of the Section on Intracellular Protein Trafficking, NICHD, NIH. In 2008, he was appointed NIH Distinguished Investigator. Since the early 1990s, Dr. Bonifacino's group at the NIH has been conducting research on signals and adaptor proteins that mediate the sorting of proteins to endosomes, lysosomes, lysosome-related organelles such as melanosomes, and different domains of the plasma membrane in polarized cells such as neurons. His group discovered new sorting signals and adaptor proteins, and applied this knowledge to the elucidation of the causes and mechanisms of various disease conditions, including the Hermansky-Pudlak syndrome type 2 (HPS-2) and AP-4-deficiency syndrome. In addition, Dr. Bonifacino’s group identified novel components of the molecular machinery involved in retrograde transport from endosomes to the trans-Golgi network (TGN), and in recycling from endosomes to the plasma membrane. More recently, Dr. Bonifacino has expanded the scope of his research to the molecular mechanisms that control the movement of endosomes and lysosomes in non-neuronal and neuronal cells, and the connection of these mechanisms to various neurodevelopmental and early-infantile neurodegenerative disorders.

Dr. Bonifacino is an elected member of the American Academy of Arts and Sciences, fellow of the American Association for the Advancement of Sciences, fellow of the American Society for Cell Biology, and the recipient of the University of Utrecht Van Deenen Medal, Keith Porter Lecture Award, Raíces Award, and the NICHD Lifetime Achievement Award. He is an Honorary Professor of Biological Chemistry at the University of Buenos Aires, and Sackler Lecturer at Tel-Aviv University. He was a member of the Council of the American Society for Cell Biology (ASCB) and chaired various scientific conferences. He has delivered many named lectures, including the Alex Novikoff, Leonardo Satz, G. Burroughs Mider, Jesús Adolfo García Sanz, Hughlings Jackson, Peter Maloney, Federico Leighton, Oscar Orías, Héctor Torres, and Andrew Somlo Lectures. He has served in various editorial capacities at the journals Developmental Cell, Molecular Cell, Journal of Cell Biology, Molecular Biology of the Cell, Journal of Biological Chemistry and Traffic. He was the co-editor of the books Current Protocols in Cell Biology and Short Protocols in Cell Biology. His lab has trained over 100 post-doctoral fellows and students, many of whom have pursued careers in academic research.