Kylie J. Walters, Ph.D.

Kylie J. Walters, Ph.D.
Acting Chief
Senior Investigator
Head, Protein Processing Section

A primary research emphasis of the Walters lab is to define the mechanistic determinants of regulated protein degradation by the proteasome and of protein quality control pathways. Dysfunction of these processes is associated with disease, and specific inhibitors of machinery critical to protein clearance are used as anti-cancer therapeutics. The Walters lab comprises a vibrant assembly of researchers with diverse expertise, enabling the seamless merger of structural and cell biology techniques. Methodology ranges from NMR spectroscopy and cryoelectron microscopy to CRISPR-based gene editing and state-of-the-art sequencing. The group has made key discoveries that have helped define how the proteasome recognizes its substrates and established a new approach to target the ubiquitin-proteasome pathway that has clinical promise.

Areas of Expertise
1) proteasome 2) ubiquitin signaling 3) structural biology 4) NMR 5) protein quality control

Contact Info

Kylie J. Walters, Ph.D.
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

Scientific Focus Areas:
Biomedical Engineering and Biophysics, Cancer Biology, Molecular Biology and Biochemistry, Molecular Pharmacology, Structural Biology
View Dr. Walters' PubMed Summary.

Selected Key Publications

  1. He F, Wollscheid HP, Nowicka U, Biancospino M, Valentini E, Ehlinger A, Acconcia F, Magistrati E, Polo S, Walters KJ.
    Cell Rep. 14(11): 2683-94, 2016. [ Journal Article ]
  2. Shi Y, Chen X, Elsasser S, Stocks BB, Tian G, Lee BH, Shi Y, Zhang N, de Poot SA, Tuebing F, Sun S, Vannoy J, Tarasov SG, Engen JR, Finley D, Walters KJ
    Science. 351: pii: aad9421, 2016. [ Journal Article ]
  3. Randles L, Anchoori RK, Roden RB, Walters KJ
    J. Biol. Chem. 291: 8773-83, 2016. [ Journal Article ]
  4. Chen X, Randles L, Shi K, Tarasov SG, Aihara H, Walters KJ
    Structure. 24: 1257-70, 2016. [ Journal Article ]
  5. Lu X, Nowicka U, Sridharan V, Liu F, Randles L, Hymel D, Dyba M, Tarasov SG, Tarasova NI, Zhao XZ, Hamazaki J, Murata S, Burke TR Jr, Walters KJ
    Nat. Commun. 8: 15540, 2017. [ Journal Article ]

Dr. Walters merges structural and cellular biology approaches to define the mechanisms of regulated protein degradation and quality control. Together with her collaborators and team members, she has made seminal scientific contributions that have defined how the proteasome recognizes its ubiquitinated substrates. These findings have led to new therapeutic strategies for cancer treatment. Dr. Walters’ training in the field of biophysics began as an undergraduate at Wesleyan University, where she used NMR to study the dynamic properties of DNA. She then obtained a Ph.D. in Biophysics from Harvard University, where she developed and used methods to study protein structure, dynamics, and interaction mechanisms. As an American Cancer Society Postdoctoral Fellow with Dr. Peter Howley in the Pathology Department at Harvard Medical School, she defined how a shuttle factor of the ubiquitin signaling pathway binds to the proteasome. 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 studied the mechanism by which ubiquitin signals for degradation by the proteasome. Dr. Walters was also awarded an American Cancer Society Research Scholarship from 2007-2011 for her work in protein quality control. In 2013, she moved to the Center for Cancer Research as a Senior Investigator, where she runs a vibrant research program that aims to apply basic science discoveries to translational benefit in the clinic. She currently serves on the CCR Science Board and as Acting Chief of the Structural Biophysics Laboratory.

Name Position
Gwen Buel Ph.D. Postdoctoral Fellow (CRTA)
Xiang Chen, Ph.D. Staff Scientist
Danielle Ebelle Postbaccalaureate Fellow (CRTA)
Olumide Kayode Ph.D. Postdoctoral Fellow (CRTA)
Xiuxiu Lu Ph.D. Postdoctoral Fellow (Visiting)
Brandon J. Wright Ph.D. Postdoctoral Fellow (CRTA)
Vinidhra Sridharan Postdoctoral Fellow 8/2016-11/2018

Current position: Scientist at Celgene Corporation

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Evan Hooper Student 6/2017-5/2018

Current position: Undergraduate Student at Florida State University

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Fahu He Research Fellow (VP) 6/2013-11/2016

Current position: NMR Facility Manager, St. Louis University

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Urszula Nowicka Postdoctoral Fellow 7/2014-11/2016

Current position: Scientific Advisor, Center of New Technologies, University of Warsaw

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Sarah Durham Student 6/2015-8/2016

Current position: Undergraduate student at Lebanon Valley College

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Fen Liu, Ph.D. Research Fellow (VP) 6/2013-7/2016

Current Position: Principle Scientific Consultant, 100BioTech, Co. Ltd.

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Leah A. Randles, Ph.D. Postdoctoral Fellow; Graduate Student 01/2013-05/2016; 2/2007-12/2012

Current position: Chemist, Syntiron

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Jacob Vannoy Student 6/2014-8/2015; 3/2017-8/2017

Current position: Student at University of Virginia

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Morgan Hoffman Student 06/2014-08/2015

Current position: Undergraduate student at University of Maryland, College Park

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Yanhong Shi, Ph.D. Sabbatical Visiting Professor 7/2013-8/2014

Current position: Faculty at Shanghai Institute of Materia Medica

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Aaron C. Ehlinger, Ph.D. Graduate Student 2/2008-7/2013

Current position: Postdoctoral Fellow at Vanderbilt University

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Molly Westfield High School Researcher summer 2012

Current position: Undergraduate student at the University of Minnesota

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Kimberly Wadsworth, Ph.D. Postdoctoral Fellow 5/2009-5/2011

Current position: Senior Immunogenetic Specialist at Be The Match operated by National Marrow Donor Program

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Yang Kang, Ph.D., DDS PhD Grad Student and Postdoctoral Fellow 9/2003-6/2010

Current position: Assistant Clinical Professor at University of New England, Maine

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Naixia Zhang, Ph.D. Research Assistant Professor 5/2004-2/2010

Current position: Faculty at Shanghai Institute of Materia Medica

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William Casey Solomon, Ph.D. Undergraduate Student Researcher 1/2008-6/2009

Current position: Visiting Assistant Chemistry Professor, St Olaf College

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Cheryl Ethan, Ph.D. Research Specialist 3/2007-6/2007

Current position: Research Scientist, R&D Systems Inc.

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Qinghua Wang, Ph.D. PhD Grad Student and Postdoctoral Associate 1/2002-9/2006

Current position: Instructor, University of Delaware

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Nathan Winter, Ph.D. Sabbatical Visiting Professor 1/2004-6/2004

Current position: Professor at St Cloud State University Department of Chemistry

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Congratulations to Dr. Xiuxiu Lu for receiving a Best Poster Award at the 2018 NCI Structural Biology Retreat

Structural Biophysics Laboratory 2018 Retreat - Poster session

Congratulations to Dr. Xiang Chen and Dr. Kylie Walters for receiving CCR Federal Technology Transfer Awards

Congratulations to Dr. Gwen Buel for being selected as a winner of NIH Fellows Award for Research Excellence (FARE) 2019 competition.

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.

The Protein Processing Section pose for a photo during the summer of 2018