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

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.

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

Contact Info

Kylie J. Walters, Ph.D.
Center for Cancer Research
National Cancer Institute
Building 538, Room 140B
Frederick, MD 21702
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 are interested in how protein substrates are recognized and ubiquitinated by cellular surveillance systems and how ubiquitinated substrates are identified and processed by  proteasome. 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 proteasome recognizes and processes its substrates.

In previous work, we solved the structures of two proteasome ubiquitin receptors S5a and hRpn13 complexed with ubiquitin to learn features that allow these two proteins to synergistically recruit ubiquitinated substrates. We have also solved the structure of a receptor that shuttles ubiquitinated substrates to    proteasome and revealed dynamic properties of a proteasome ATPase. We continue to study protein-protein interactions in proteasome and other cellular processes by NMR, allowing us to solve 3-dimensional structures and reveal dynamic behaviors that contribute to function. In ongoing work, we use this knowledge to characterize interactions between proteasome components and agents that exhibit anti-cancer effects.

In parallel, we use functional assays to interrogate structure-based predictions in cells and to further characterize protein quality control systems. We seek to understand the determinants of protein targeting for degradation by proteasome and the machinery that goes awry during carcinogenesis and neurological disorders.

Scientific Focus Areas:
Cancer Biology, Molecular Biology and Biochemistry, Structural Biology

View Dr. Walters' PubMed Summary.

Selected Key Publications
  1. Anchoori RK, Karanam B, Peng S, Wang JW, Jiang R, Tanno T, Orlowski RZ, Matsui W, Zhao M, Rudek MA, Hung CF, Chen X, Walters KJ, Roden RB.
    Cancer Cell. 24: 791-805, 2013. [ Journal Article ]
  2. Chen X, Lee BH, Finley D, Walters KJ.
    Mol. Cell. 38: 404-15, 2010. [ Journal Article ]
  3. Zhang N, Wang Q, Ehlinger A, Randles L, Lary JW, Kang Y, Haririnia A, Storaska AJ, Cole JL, Fushman D, Walters KJ.
    Mol. Cell. 35: 280-90, 2009. [ Journal Article ]
  4. Husnjak K, Elsasser S, Zhang N, Chen X, Randles L, Shi Y, Hofmann K, Walters KJ, Finley D, Dikic I.
    Nature. 453: 481-8, 2008. [ Journal Article ]
  5. Schreiner P, Chen X, Husnjak K, Randles L, Zhang N, Elsasser S, Finley D, Dikic I, Walters KJ, Groll M.
    Nature. 453: 548-52, 2008. [ 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, she 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. She was an American Cancer Society Research Scholar from 2007-2011 and in 2013, joined the Structural Biophysics Laboratory at NCI.

Name Position
Xiang Chen Research Fellow
Fahu He Research Fellow
Morgan Hoffman Student Intern
Fen Liu Research Fellow
Xiuxiu Lu Ph.D. Postdoctoral Fellow (Visiting)
Urszula Nowicka Postdoctoral Fellow (Visiting)
Leah A. Randles, Ph.D. Postdoctoral Fellow (CRTA)
Jacob Vannoy Student Intern

Research

The Walters lab studies the structural and mechanistic basis of ubiquitin signaling events, proteasome function, and protein quality control. We are interested in how protein substrates are recognized and ubiquitinated by cellular surveillance systems and how ubiquitinated substrates are identified and processed by  proteasome. 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 proteasome recognizes and processes its substrates.

In previous work, we solved the structures of two proteasome ubiquitin receptors S5a and hRpn13 complexed with ubiquitin to learn features that allow these two proteins to synergistically recruit ubiquitinated substrates. We have also solved the structure of a receptor that shuttles ubiquitinated substrates to    proteasome and revealed dynamic properties of a proteasome ATPase. We continue to study protein-protein interactions in proteasome and other cellular processes by NMR, allowing us to solve 3-dimensional structures and reveal dynamic behaviors that contribute to function. In ongoing work, we use this knowledge to characterize interactions between proteasome components and agents that exhibit anti-cancer effects.

In parallel, we use functional assays to interrogate structure-based predictions in cells and to further characterize protein quality control systems. We seek to understand the determinants of protein targeting for degradation by proteasome and the machinery that goes awry during carcinogenesis and neurological disorders.

Scientific Focus Areas:
Cancer Biology, Molecular Biology and Biochemistry, Structural Biology

Publications

View Dr. Walters' PubMed Summary.

Selected Key Publications
  1. Anchoori RK, Karanam B, Peng S, Wang JW, Jiang R, Tanno T, Orlowski RZ, Matsui W, Zhao M, Rudek MA, Hung CF, Chen X, Walters KJ, Roden RB.
    Cancer Cell. 24: 791-805, 2013. [ Journal Article ]
  2. Chen X, Lee BH, Finley D, Walters KJ.
    Mol. Cell. 38: 404-15, 2010. [ Journal Article ]
  3. Zhang N, Wang Q, Ehlinger A, Randles L, Lary JW, Kang Y, Haririnia A, Storaska AJ, Cole JL, Fushman D, Walters KJ.
    Mol. Cell. 35: 280-90, 2009. [ Journal Article ]
  4. Husnjak K, Elsasser S, Zhang N, Chen X, Randles L, Shi Y, Hofmann K, Walters KJ, Finley D, Dikic I.
    Nature. 453: 481-8, 2008. [ Journal Article ]
  5. Schreiner P, Chen X, Husnjak K, Randles L, Zhang N, Elsasser S, Finley D, Dikic I, Walters KJ, Groll M.
    Nature. 453: 548-52, 2008. [ Journal Article ]

Biography

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, she 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. She was an American Cancer Society Research Scholar from 2007-2011 and in 2013, joined the Structural Biophysics Laboratory at NCI.

Team

Name Position
Xiang Chen Research Fellow
Fahu He Research Fellow
Morgan Hoffman Student Intern
Fen Liu Research Fellow
Xiuxiu Lu Ph.D. Postdoctoral Fellow (Visiting)
Urszula Nowicka Postdoctoral Fellow (Visiting)
Leah A. Randles, Ph.D. Postdoctoral Fellow (CRTA)
Jacob Vannoy Student Intern