Valerie Daggett

Professor

daggett@uw.edu
Phone: (206)685-7420
Office: Foege N310B

UW Bioengineering faculty Valerie Daggett

Lab Website

How I am inventing the future of medicine

My laboratory is using computational and experimental methods to design diagnostic and therapeutic agents to target amyloid diseases, which are reaching epidemic proportions as human lifespan increases.
Research Interests

Protein folding & dynamics
Dynameomics/bioinformatics
Extremophile proteins
Protein modulators
Protein design
Unfolding diseases
Protein complexes
Single nucleotide polymorphisms
Research Description

Our work spans software development to biological assays of neurotoxicity. We have active programs investigating protein dynamics, folding and misfolding, particularly as related to human mutations and various diseases. We have developed a molecular modeling and simulation package, which we have used to simulate the native state dynamics and unfolding/folding of representatives of essentially all known protein folds (95%) in an effort we refer to as Dynameomics. Novel databases and mining methods are being developed for this large dataset (hundreds of terabytes) comprising the largest collection of protein simulations and structures in the world. We are using this resource to develop tools for protein modeling and design. These tools and associated simulations are already being used to design diagnostic and therapeutic agents for amyloid diseases. The computational designs have been synthesized and are being tested in four different amyloid systems: transthyretin (systemic amyloidosis), Abeta (Alzheimer’s Disease), amylin (type 2 diabetes) and the prion protein (transmissible spongiform encephalopathies). And, in very recent studies, these designed compounds are also being tested for their ability to block bacterial biofilm formation.
Education

PhD, Pharmaceutical Chemistry, University of California San Francisco
BA, Reed College, 1983
Postdoc Information

Postdoctoral Fellow, Stanford University 1990-1993
Awards and Honors

Lise Meitner Visiting Professorship, Lund University
Senior Editor, Protein Engineering, Design and Selection
Editorial Boards: Biochemistry, Current Opinion in Structural Biology, Structure, and elife.
UW Bioengineering Courses Taught

BIOEN 315: Biochemical and Molecular Bioengineering
BIOEN 488/588: Computational Protein Design
BIOEN 530: Literary Analysis
Selected Publications

Daggett, V., Protein Folding―Simulation, Chemical Reviews, 106, 1898-1916, 2006.

Daggett, V. Alpha-sheet: The toxic conformer in amyloid diseases? Acc. Chem. Res., 39, 594-602, 2006.

Rutherford, K. and V. Daggett. Polymorphisms and Disease: Hotspots of Inactivation in Methyltransferases, Trends in Biochem. Sci., 35, 531-538, 2010.

Van der Kamp, M.W., Anderson, P.C., Beck, D.A.C., Benson, N.C., Jonsson, A.L., Merkley, E.D., Schaeffer, R.D., Scouras, A.D., Simms, A., Toofanny, R.D., and V. Daggett. Dynameomics: A comprehensive database of protein dynamics. Structure, 18, 423-435, 2010.

Schaeffer, R.D., Jonsson, A.L., Simms, A.M. and V. Daggett. Generation of a Consensus Protein Domain Dictionary, Bioinformatics, 27, 46-54, 2011.

Towse C.L., Daggett V. When a domain is not a domain, and why it is important to properly filter proteins in databases. BioEssays, 34:1060-1069, 2012.

McCully M.E., Beck D.A.C., Daggett V. Multimolecule test-tube simulations of protein unfolding and aggregation. Proc. Natl. Acad. Sci. USA, 109, 17851-17856 2012.

McCully, M.E., Beck, D.A.C. and V. Daggett. Promiscuous contacts and heightened dynamics increase thermostability in engineered proteins, Prot. Eng. Des. Selec., 26, 34-45, 2013.

 

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