Kylie J. Walters, Ph.D.
Dr. Walters has been at the forefront of using NMR spectroscopy to determine the structure of proteins and their complexes. Her recent research has focused on targeted protein degradation via proteasome, a therapeutic target for hematological cancers.
As Head of the Protein Processing Section, Dr. Walters oversees efforts to dissect mechanisms of ubiquitin signaling pathways and protein quality control. Her lab combines biophysical and cell biology techniques with a long-term goal of discovering novel targets for preventing cancer cell proliferation.
Contact Info
Center for Cancer Research
National Cancer Institute
Advanced Technology Research Facility (ATRF)/B3330
Frederick, MD 21702
Ph: 301-228-4374
kylie.walters@nih.gov
The Walters lab studies the structural and mechanistic basis of ubiquitin signaling events, proteasome function, and protein quality control. We use cell-based assays and a variety of biophysical techniques, our most powerful of which is NMR spectroscopy. This approach has helped to develop a mechanistic understanding of how the proteasome recognizes and processes its substrates. Working with other labs, we have identified Rpn1 and Rpn13 as substrate receptors in the proteasome that bind to ubiquitin chains and the shuttle factors that deliver ubiquitinated substrates to the proteasome. We have found that Rpn13 is targeted in its ubiquitin-binding domain by cell permeable molecules that restrict cancer cell proliferation. This work suggests that Rpn13 is a viable therapeutic target for human cancers. Small molecules that inhibit the catalytic core particle of the proteasome are approved for treatment of hematological cancers. Targeting of Rpn13 is expected to function synergistically with these approved molecules. We continue to study protein-protein interactions in the proteasome and other quality control pathways to understand the determinants of protein targeting for degradation as well as the mechanistic features that go awry in these pathways during carcinogenesis and neurological disorders.
Postdoctoral Fellowships
The Protein Processing Section currently has an opening for an outstanding postdoctoral fellow. If you are interested in joining us, please send your C.V. and a statement of interest to kylie.walters@nih.gov
Selected Key Publications
- Cell Rep. 14(11): 2683-94, 2016. [ Journal Article ]
- Science. 351: pii: aad9421, 2016. [ Journal Article ]
- J. Biol. Chem. 291: 8773-83, 2016. [ Journal Article ]
- Structure. 24: 1257-70, 2016. [ Journal Article ]
- Nat. Commun. 8: 15540, 2017. [ Journal Article ]
Dr. Walters obtained her Ph.D. in Biophysics from Harvard University, where she used NMR spectroscopy to study protein structure and dynamics in Dr. Gerhard Wagner's laboratory. As an American Cancer Society Postdoctoral Fellow with Dr. Peter Howley in the Pathology Department at Harvard Medical School, she studied the ubiquitin signaling pathway. In 2002, Dr. Walters joined the University of Minnesota as an Assistant Professor and was promoted to Associate Professor with tenure in 2008. During this time, her lab used NMR spectroscopy to study ubiquitin signaling for degradation by proteasome. Dr. Walters was an American Cancer Society Research Scholar from 2007-2011. In 2013, she joined the Structural Biophysics Laboratory at the CCR as a Senior Investigator. She was elected as a CCR Women Science Advisor in 2016 and serves on the CCR Science Board.
| Name | Position |
|---|---|
| Gwen Buel Ph.D. | Postdoctoral Fellow (CRTA) |
| Xiang Chen, Ph.D. | Staff Scientist |
| Danielle Ebelle | Postbaccalaureate Fellow (CRTA) |
| Evan Hooper | Werner H. Kirsten Student Intern |
| Olumide Kayode Ph.D. | Postdoctoral Fellow (CRTA) |
| Xiuxiu Lu Ph.D. | Postdoctoral Fellow (Visiting) |
| Vinidhra Sridharan Ph.D. | Postdoctoral Fellow (CRTA) |
| Brandon J. Wright Ph.D. | Postdoctoral Fellow (CRTA) |
Current position: NMR Facility Manager, St. Louis University
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Current position: Scientific Advisor, Center of New Technologies, University of Warsaw
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Current position: Undergraduate student at Lebanon Valley College
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Current Position: Principle Scientific Consultant, 100BioTech, Co. Ltd.
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Current position: Chemist, Syntiron
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Current position: Student at University of Virginia
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Current position: Undergraduate student at University of Maryland, College Park
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Current position: Faculty at Shanghai Institute of Materia Medica
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Current position: Postdoctoral Fellow at Vanderbilt University
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Current position: Undergraduate student at the University of Minnesota
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Current position: Senior Immunogenetic Specialist at Be The Match operated by National Marrow Donor Program
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Current position: Assistant Clinical Professor at University of New England, Maine
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Current position: Faculty at Shanghai Institute of Materia Medica
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Current position: Visiting Assistant Chemistry Professor, St Olaf College
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Current position: Research Scientist, R&D Systems Inc.
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Current position: Instructor, University of Delaware
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Current position: Professor at St Cloud State University Department of Chemistry
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Congratulations to Dr. Xiang Chen for being selected as a winner of NIH Fellows Award for Research Excellence (FARE) 2017 competition. Xiang used this award to attend and present a poster at Cold Spring Harbor Laboratory Conference “The ubiquitin Family” on April 18-22, 2017.
Congratulations to Dr. Xiuxiu Lu for being selected to give an oral presentation at the ASBMB 2017 meeting in Chicago on April 22-26.
Dr. Vinidhra Sridharan presented a poster at the Cold Spring Harbor Laboratory Conference “The Ubiquitin Family”, April 18-22, 2017.