Nicolas Lux FawziAssistant Professor of Molecular Pharmacology, Physiology and Biotechnology
Nicolas Fawzi's work centers on determining the structure, dynamics, interactions of large assemblies of intrinsically disordered proteins. In particular, we focus on 1) protein aggregates implicated in Alzheimer’s Disease and 2) liquid-liquid phase separated forms of RNA-binding proteins associated with inclusion formation in amyotrophic lateral sclerosis (ALS / Lou Gehrig's disease) and frontotemporal dementia. He received undergraduate degrees in bioengineering and marketing at the University of Pennsylvania. He received a Ph.D. from the Joint Graduate Group in Bioengineering at the University of California, Berkeley and UCSF for his work with Teresa Head-Gordon on molecular simulation of protein aggregation, and completed postdoctoral training in the group of G. Marius Clore at the National Institutes of Health in biomolecular NMR spectroscopy of protein association and aggregation. Nicolas Fawzi joined the faculty at Brown in January 2013.
Burke, KA, Janke, AM, Rhine, CL & Fawzi, NL†. Residue-by-Residue View of In Vitro FUS Granules that Bind the C-Terminal Domain of RNA Polymerase II. Molecular Cell. 60:231-41. (2015)
Conicella AE, Fawzi NL†. The C-terminal threonine of Aβ43 nucleates toxic aggregation via structural and dynamical changes in monomers and protofibrils. Biochemistry. 53:3095-105. (2014)
Fawzi NL†, Libich DS,Ying J, Tugarinov V., Clore GM†. Characterizing methyl-bearing side chain contacts and dynamics mediating amyloid β protofibril interactions using 13Cmethyl-DEST and lifetime line broadening. Angew Chem Int Ed Engl. 53:10345-9. (2014)
Libich, DS, Fawzi, NL, Ying, J, Clore, GM. Probing the transient dark state of substrate binding to GroEL by relaxation-based solution NMR. Proceedings of the National Academy of Sciences U S A, 110, 11361-6. (2013).
Fawzi NL, Ying J, Torchia DA, Clore GM. Probing exchange kinetics and atomic resolution dynamics in high-molecular-weight complexes using dark-state exchange saturation transfer NMR spectroscopy. Nat Protoc. 7: 1523-1533. (2012).
Ball KA, Phillips AH, Nerenberg PS, Fawzi NL, Wemmer DE, Head-Gordon T. Homogeneous and heterogeneous tertiary structure ensembles of amyloid-beta peptides. Biochemistry. 50: 7612-7628. (2011).
Fawzi NL, Fleissner MR, Anthis NJ, Kalai T, Hideg K, Hubbell WL, Clore GM. A rigid disulfide-linked nitroxide side chain simplifies the quantitative analysis of PRE data. J Biomol NMR. 51: 105-114. (2011).
Fawzi NL, Ying J, Ghirlando R, Torchia DA, Clore GM. Atomic-resolution dynamics on the surface of amyloid-beta protofibrils probed by solution NMR. Nature. 480: 268-272. (2011).
Fawzi NL, Ying J, Torchia DA, Clore GM. Kinetics of amyloid beta monomer-to-oligomer exchange by NMR relaxation. J Am Chem Soc. 132: 9948-9951. (2010).
Fawzi NL, Doucleff M, Suh JY, Clore GM. Mechanistic details of a protein-protein association pathway revealed by paramagnetic relaxation enhancement titration measurements. Proc Natl Acad Sci U S A. 107: 1379-1384. (2010).
Fawzi NL, Okabe Y, Yap EH, Head-Gordon T. Determining the critical nucleus and mechanism of fibril elongation of the Alzheimer's Abeta(1-40) peptide. J Mol Biol. 365: 535-550. (2007).
Marianayagam NJ, Fawzi NL, Head-Gordon T. Protein folding by distributed computing and the denatured state ensemble. Proc Natl Acad Sci U S A. 102: 16684-16689. (2005).
Brown S, Fawzi NJ, Head-Gordon T. Coarse-grained sequences for protein folding and design. Proc Natl Acad Sci U S A. 100: 10712-10717. (2003).
My laboratory studies the structure, dynamics, and molecular interactions of protein granule assembly and protein aggregates implicated in neurodegenerative disease. Using a combination of novel NMR spectroscopy approaches and atomistic simulation supplemented by biophysical and imaging methods, we determine high-resolution structures of these species and their toxic interactions with other macromolecules and membranes, as well as their interactions with potential therapeutic agents.
The goal of my research group is to determine the structure and elucidate the molecular mechanisms of toxicity of aggregated and aggregation-prone states of proteins in neurodegenerative disease. My current aims are directed at RNA-binding proteins involved in ALS and frontotemporal dementias as well as amyloid-β aggregation associated with Alzheimer's Disease.
Center of Biomedical Research Excellence (COBRE) for Skeletal Health and Repair, Pilot Project
"Seeds of protein aggregation in inclusion body myositis"
9/1/2013 - 8/31/2016
Role: Junior Investigator (PI: Chen)
The major goal of this pilot project is to develop a molecular picture of aggregation of hnRNP proteins in inclusion body myositis and myopathy.
Rhode Island Foundation, Medical Research Grant
"Finding the molecular switch of FUS protein aggregation in neurodegeneration"
3/1/2014 - 2/28/2015
The major goal of this project is to determine how ALS-causing mutations and post-translation modifications in the protein FUS affect aggregation
RI-INBRE Research Proposal Development Project
"Structural Characterization of Soluble and Neurotoxic Aggregates of FUS"
11/15/2012 - 4/30/2013
Role: Development Project PI
The goal of this project is to develop the protocols for recombinant protein expression and purification of FUS, a human RNA binding protein that forms neuronal inclusions in ALS and frontotemporal dementia.
2002 Graduate Fellow, Whitaker Foundation
2012 Sacconi Centennial Grant, 12th Chianti/INSTRUCT Workshop on BioNMR
2012 Postdoctoral Research Award, Division of Physical Chemistry Division, American Chemical Society
Bennett, Richard Professor of Biology, Co-Director of the Pathobiology Graduate Program
Larschan, Erica Richard and Edna Salomon Assistant Professor of Molecular Biology, Cell Biology and Biochemistry, Assistant Professor of Biology
2005-present Member of American Chemical Society
2010-present Member of Biophysical Society
G. Marius Clore group NIDDK.
BIOL1300 Biomolecular Interactions: Health, Disease, and Drug Design, Fall, Monday 3-5:30pm
BIOL 1300 - Biomolecular Interactions: Health, Disease and Drug Design. Fall 2014, Fall 2015.