Juan S. Bonifacino, Ph.D.

NIH Distinguished Investigator

Section on Intracellular Protein Trafficking

NICHD/DIR

NIHBC 35A - PNRC II 2F-226
20892-3758

301-496-6368

juan.bonifacino@nih.gov

Research Topics

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 various 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 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 disease protein trafficking diseases such as the pigmentation and bleeding disorder Hermansky-Pudlak syndrome (HPS), the neuro-cutaneous disorder MEDNIK syndrome and a subset of hereditary spastic paraplegias. In addition, we study how the molecular mechanisms of protein transport are exploited by intracellular pathogens such as HIV-1.

Biography

Dr. Juan 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 Associate Scientific Director for the Cell Biology and Neurobiology Branch, NICHD, NIH. In 2008, he was appointed NIH Distinguished Investigator. Since the early 1990s, Dr. Bonifacino's group has conducted research on signals and adaptor proteins that mediate protein sorting to endosomes and lysosomes. His group discovered new sorting signals and adaptor proteins, and applied this knowledge to the elucidation of the causes of various human diseases including the Hermansky-Pudlak syndrome type 2 and autosomal dominant polycystic liver disease. Dr. Bonifacino has served in various editorial capacities for the journals Developmental Cell, Molecular Cell, Molecular Biology of the Cell, Journal of Cell Biology, Journal of Biological Chemistry and Traffic. He is also the co-editor of the books Current Protocols in Cell Biology and Short Protocols in Cell Biology. He served as a member of the Council of the American Society for Cell Biology, and chaired various scientific conferences. He has delivered the Alex Novikoff, Leonardo Satz, G. Burroughs Mider, Hughlings Jackson and Peter Maloney lectures, and is an Honorary Professor of Biological Chemistry at the University of Buenos Aires. He was appointed Fellow of the American Society for Cell Biology. His lab has trained over 70 postdoctoral fellows and students, most of whom have pursued careers in academic research.

Selected Publications

  1. Ballabio A, Bonifacino JS. Lysosomes as dynamic regulators of cell and organismal homeostasis. Nat Rev Mol Cell Biol. 2020;21(2):101-118.

  2. Keren-Kaplan T, Bonifacino JS. ARL8 Relieves SKIP Autoinhibition to Enable Coupling of Lysosomes to Kinesin-1. Curr Biol. 2021;31(3):540-554.e5.

  3. De Pace R, Britt DJ, Mercurio J, Foster AM, Djavaherian L, Hoffmann V, Abebe D, Bonifacino JS. Synaptic Vesicle Precursors and Lysosomes Are Transported by Different Mechanisms in the Axon of Mammalian Neurons. Cell Rep. 2020;31(11):107775.

  4. Jia R, Bonifacino JS. The ubiquitin isopeptidase USP10 deubiquitinates LC3B to increase LC3B levels and autophagic activity. J Biol Chem. 2021;296:100405.

  5. Saric A, Freeman SA, Williamson CD, Jarnik M, Guardia CM, Fernandopulle MS, Gershlick DC, Bonifacino JS. SNX19 restricts endolysosome motility through contacts with the endoplasmic reticulum. Nat Commun. 2021;12(1):4552.


This page was last updated on October 19th, 2019