BIOGRAPHICAL SKETCH Provide the following information for the key personnel and other significant contributors in the order listed on Form Page 2. Follow this format for each person. DO NOT EXCEED FOUR PAGES. NAME Hughson, Frederick M. POSITION TITLE Associate Professor of Molecular Biology eRA COMMONS USER NAME fhughson EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, and include postdoctoral training.) DEGREE (if applicable) YEAR(s) Yale University, New Haven, CT B.S. 1984 Stanford University, Stanford, CA Ph.D. 1990 Postdoctoral Fellow 1990-1994 INSTITUTION AND LOCATION Harvard University, Cambridge, MA FIELD OF STUDY Molecular Biophysics & Biochemistry Biochemistry Biochemistry A. Positions and Honors. Positions and Employment 1984-1990 Graduate Fellow, Stanford Department of Biochemistry Robert L. Baldwin, advisor. Research: protein folding. 1990-1994 Postdoctoral Fellow, Harvard Dept. of Biochemistry & Molecular Biology Don C. Wiley, advisor. Research: X-ray crystal structure of low-pH hemagglutinin. 1994-2002 Assistant Professor of Molecular Biology, Princeton University 2002Associate Professor of Molecular Biology, Princeton University 2006Director, HHMI Undergraduate Science Education Program at Princeton Honors 1983 1984 1984-1987 1990-1994 1991-1994 1995-1998 1995-1997 20012003- Sigma Xi Summa cum laude, Yale University NSF Predoctoral Fellowship Helen Hay Whitney Postdoctoral Fellowship Harvard Board of Tutors Searle Scholar Beckman Young Investigator Member, Faculty of 1000 Editorial Board, PLoS Biology B. Selected peer-reviewed publications (in chronological order). 1. 2. 3. 4. 5. 6. Hughson, F.M. and Baldwin, R.L. (1989) Use of site-directed mutagenesis to destabilize native apomyoglobin relative to folding intermediates. Biochemistry 28, 4415-4422. Hughson, F.M., Wright, P.E. and Baldwin, R.L. (1990) Structural characterization of a partly folded apomyoglobin intermediate. Science 249, 1544-1548. Hughson, F.M., Barrick, D. and Baldwin, R.L. (1991) Probing the stability of a partly folded apomyoglobin intermediate by site-directed mutagenesis. Biochemistry 30, 4413-4418. Barrick, D., Hughson, F.M., and Baldwin, R.L. (1994) Molecular mechanisms of acid denaturation: the role of histidine residues in the partial unfolding of apomyoglobin. J. Mol. Biol. 237, 588-601. Bullough, P.A., Hughson, F.M., Treharne, A.C., Ruigrok, R.W.H., Skehel, J.J., and Wiley, D.C. (1994) Crystals of a fragment of influenza haemagglutinin in the low pH induced conformation. J. Mol. Biol. 236, 1262-1265. Bullough, P.A.*, Hughson, F.M.*, Skehel, J.J., and Wiley, D.C. (1994) The structure of influenza haemagglutinin at the pH of membrane fusion. Nature 371, 37-43. *Authors contributed equally. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. Hughson, F.M. (1995) Structural characterization of viral fusion proteins [review]. Curr. Biol. 5, 265-274. Hughson, F.M. (1995) Molecular mechanisms of protein-mediated membrane fusion [review]. Curr. Opin. Struct. Biol. 5, 507-513. Chen, J., Wharton, S.A., Weissenhorn, W., Calder, L.J., Hughson, F.M., Skehel, J.J., and Wiley, D.C. (1995) A soluble domain of the membrane-anchoring chain of influenza virus hemagglutinin (HA2) folds in Escherichia coli into the low-pH-induced conformation. Proc. Natl. Acad. Sci. USA 92, 12205-12209. Hughson, F.M. (1997) Enveloped viruses: a common mode of membrane fusion? [review]. Curr. Biol. 7, R565-R569. Nicholson, K.L., Munson, M., Miller, R.B., Filip, T.J., Fairman, R., and Hughson, F.M. (1998) Regulation of SNARE complex assembly by an N-terminal domain of the t-SNARE Sso1p. Nature Struct. Biol. 5, 793-802. Hughson, F.M. (1999) Membrane fusion: structure snared at last [review]. Curr. Biol. 9, R49-R52. Carr, C.M., Grote, E., Munson, M., Hughson, F.M., and Novick, P.J. (1999) Sec1p binds to SNARE complexes and concentrates at sites of secretion. J. Cell Biol. 146, 333-344. Lerman, J.C., Robblee, J., Fairman, R., and Hughson, F.M. (2000) Structural analysis of the neuronal SNARE protein syntaxin-1A. Biochemistry 39, 8470-8479. Waters, M.G. and Hughson, F.M. (2000) Membrane tethering and fusion in the secretory and endocytic pathways [review]. Traffic 1, 588-597. Munson, M., Chen, X., Cocina, A.E., Schultz, S.M., and Hughson, F.M. (2000) Interactions within the yeast t-SNARE Sso1p that control SNARE complex assembly. Nature Struct. Biol. 7, 894-902. Chen, X., Schauder, S., Potier, N., Van Dorsselaer, A., Pelczer, I., Bassler, B.L., and Hughson, F.M. (2002) Structural identification of a bacterial quorum sensing signal containing boron. Nature 415, 545549. Barrick, D. and Hughson, F.M. (2002) Irreversible assembly of membrane fusion machines [News & Views]. Nature Struct. Biol. 9, 78-80. Munson, M. and Hughson, F.M. (2002) Conformational regulation of SNARE assembly and disassembly in vivo. J. Biol. Chem. 277, 9375-9381. Ungar, D. and Hughson, F.M. (2003) SNARE protein structure and function [review]. Ann. Rev. Cell Devel. Biol. 19, 493-517. Zweifel, M.E., Leahy, D.J., Hughson, F.M., and Barrick, D. (2003) Structure and stability of the ankyrin domain of the Drosophila Notch receptor. Protein Science 12, 2622-2632. Oka, T., Ungar, D., Hughson, F.M., and Krieger, M. (2004) The COG and COPI complexes interact to control the abundance of GEARs, a subset of Golgi integral membrane proteins. Mol. Biol. Cell 15, 24232435. Miller, S.T., Xavier, K.B., Campagna, S.R., Taga, M.E., Semmelhack, M.F., Bassler, B.L., and Hughson, F.M. (2004) Salmonella typhimurium recognizes a chemically distinct form of the bacterial quorum sensing signal AI-2. Mol. Cell 15, 677-687. Neiditch, M.B., Federle, M.J., Miller, S.T., Bassler, B.L., and Hughson, F.M. (2005) Regulation of LuxPQ receptor activity by the quorum-sensing signal autoinducer-2. Mol. Cell 18, 507-518. Ungar, D., Oka, T., Vasile, E., Krieger, M., and Hughson, F.M. (2005) Subunit architecture of the conserved oligomeric Golgi complex. J. Biol. Chem. 280, 32729-32735. Oka, T., Vasile, E., Penman, M., Novina, C.D., Dykxhoorn, D.M., Ungar, D., Hughson, F.M., Krieger, M. (2005) Genetic analysis of the subunit organization and function of the COG complex: Studies of Cog5 and Cog7 deficient mammalian cells. J. Biol. Chem. 280, 32736-32745. Ungar, D., Oka, T., Krieger, M., and Hughson, F.M. (2006) Retrograde transport on the COG railway [review]. Trends Cell Biol., 16, 113-120. Neiditch, M.B., Federle, M.J., Pompeani, A.J., Kelly, R.C., Swem, D.L., Jeffrey, P.D., Bassler, B.L., and Hughson, F.M. (2006) Ligand-induced asymmetry in histidine sensor kinase complex regulates quorum sensing. Cell 126, 1095-1108. Togneri, J., Cheng, Y.S., Munson, M., Hughson, F.M., and Carr, C.M. (2006) SNARE complex binding mode of the Sec1/Munc-18 protein, Sec1p. Proc. Natl. Acad. Sci. USA 103, 17730-17735. Cavanaugh, L.F., Chen, X., Richardson, B.C., Ungar, D., Pelczer, I., Rizo, J., Hughson, F.M. (2007) Structural analysis of conserved oligomeric golgi complex subunit 2. J. Biol. Chem. 282, 23418-23426. 31. 32. Neiditch, M.B., Hughson, F.M. (2007) The regulation of histidine sensor kinase complexes by quorum sensing signal molecules. Methods Enzymol. 423, 250-263. Hughson, F.M. (2008) Both layers of the COPII coat come into view [review]. Cell 134, 384-385. C. Research Support Ongoing Research Support R01 AI054442 Hughson (PI) 3/1/2003 - 2/29/2013 NIH - NIAID Structure-Function Analysis of AI-2 Quorum Sensing This project is focused on studies of bacterial signaling via AI-2 and CAI-1. Goals are mechanistic studies of LuxPQ as a model for two-component signaling; discovery and mechanistic studies of LuxPQ antagonists and agonists; determination of the mechanism of CAI-1 synthesis; and studies of the recognition and transduction of the CAI-1 signal. Co-investigators are Bonnie Bassler and Martin Semmelhack, both at Princeton University. R01 GM071574 Hughson (PI) 3/1/2005 - 2/28/2009 NIH - NIGMS Structural Analysis of Golgi Trafficking Proteins This project is focused on elucidating the overall architecture of the conserved oligomeric Golgi (COG) complex, identifying COG-interacting proteins, determining the structure of the yeast Cog2 subunit, and determining the structures of other COG subunits as well as larger subassemblies. Completed Research Support AHA 0355657T Hughson (PI) 7/1/2003 – 6/30/2006 American Heart Association Heritage Affiliate Grant-In-Aid Structure of Yeast Cog2p The main goal of this grant was to use NMR spectroscopy to initiate characterization of yeast Cog2 protein.