- Senior Investigator, LCP, NIDDK, NIH, 1994-present
- Member of Technical Staff (Principal Investigator), Physical Chemistry Research Department, AT&T Bell Laboratories, 1986-1994
- Postdoctoral Researcher, University of Pennsylvania, 1984-1986
- Ph.D., University of California at Berkeley, 1984
- A.B., Princeton University, 1980
- Fellow of the American Physical Society (1997), the American Association for the Advancement of Science (2005), the International Society of Magnetic Resonance (2008), and the American Academy of Arts and Sciences (2017). Member of the National Academy of Sciences (2020).
The purpose of our research is twofold: (1) to expand the capabilities of experimental techniques, especially solid state NMR techniques, for probing structural properties of molecules with central roles in biology and human disease; (2) to provide new structural and mechanistic information about specific biomolecular systems, including protein assemblies that are associated with Alzheimer’s disease, type 2 diabetes, and AIDS.
My lab is currently pursuing several distinct but inter-related projects. We are using solid state NMR and electron microscopy to characterize molecular structures of amyloid-β fibrils, including fibrils that develop in brain tissue of Alzheimer’s disease patients. We are developing new experimental methods that allow detailed molecular structural studies of transient intermediates in processes such as protein folding, ligand binding, peptide aggregation, and protein self-assembly. We are investigating the structural and physical basis for fibril formation by low-complexity protein sequences. We are using solid state NMR and electron microscopy to characterize protein assemblies that mimic assemblies within HIV-1 and SARS-CoV-2 virions. And we are developing ultra-low-temperature methods for sensitivity enhancement in biomolecular solid state NMR and resolution enhancement in magnetic resonance imaging.
- Millisecond Time-Resolved Solid-State NMR Reveals a Two-Stage Molecular Mechanism for Formation of Complexes between Calmodulin and a Target Peptide from Myosin Light Chain Kinase.
- Jeon J, Yau WM, Tycko R.
- J Am Chem Soc (2020 Dec 16) 142:21220-21232. Abstract/Full Text
- Molecular structure of a prevalent amyloid-β fibril polymorph from Alzheimer's disease brain tissue.
- Ghosh U, Thurber KR, Yau WM, Tycko R.
- Proc Natl Acad Sci U S A (2021 Jan 26) 118. Abstract/Full Text
Research in Plain Language
We develop new methods for learning the structures of proteins and other molecules that play central roles in human disease. We apply these methods to specific problems where more conventional methods are not adequate. As an example, we developed detailed models of amyloid fibrils that are linked to Alzheimer's disease and type 2 diabetes. Our models reveal the molecular interactions that lead to amyloid formation. This knowledge may inform the design of new chemical compounds to inhibit amyloid formation and for diagnostic imaging.