Stephanie Gates, PhD

Assistant Professor

Biochemistry

Contact Information

Email sgates@missouri.edu
Phone 573-882-7968
Address 204A Schlundt Annex
Websites Google Scholar
Gates Lab
Contact

Education

  • BS, Chemistry & Biology, Millikin University, Decatur, IL
  • PhD, Chemical Biology, University of Michigan, Ann Arbor, MI
  • Postdoctoral Fellowship, University of California- Berkeley, Berkeley, CA

Research Area

Protein quality control mechanisms; Chaperone mediated proteasomal degradation; cryo-EM, single molecule FRET, enzyme kinetics

Research Description

Protein Quality Control (PQC) pathways include molecular chaperones that regulate protein folding and the substrate degradation by the Ubiquitin Proteasome System (UPS). In cancer, uncontrolled protein expression increases cellular dependence on PQC pathways, which protect, refold, or degrade misfolded proteins to promote cancer tumorigenesis. Conversely, a hallmark of neurodegeneration is the failure of PQC pathways to clear toxic proteins, including α-synuclein (Parkinson’s disease), Aβ and tau (Alzheimer’s disease). PQC pathways have a significant impact on human health, however fundamental aspects of these pathways are still not understood. My research group uses structural (cryo-EM), biophysical (smFRET), and biochemical approaches to determine how chaperones and the proteasome intersect and influence PQC.

We will mechanistically determine how chaperones interact with the proteasome, how dynamic movements of chaperones affect proteasome function, and discover novel chaperones involved in this PQC pathway. This work will provide insight into how pro-folding and pro-degradation PQC pathways promote human health and are exploited in disease. The goal is to potentially identify novel therapeutic targets involved in these PQC pathways to treat cancer and neurodegeneration.

Notable Honors and Service

  • 2019-2021 Gordon Research Seminar Chair, Stress Proteins in Growth Development and Disease Meeting
  • 2018-2022 Howard Hughes Medical Institute Postdoctoral Fellow of the Damon Runyon Cancer Research Foundation
  • 2013-2015 Chemical Biology Interface Training Fellowship

Selected Publications

  • Lee K, Thwin AC, Nadel CM, Tse E, Gates SN, Gestwicki JE, Southworth DR (2021) The structure of an Hsp90-immunophilin complex reveals cochaperone recognition of the client maturation state. Molecular Cell 81:1-13.
  • Didychuk AL, Gates SN, Gardner MR, Strong LM, Martin A, Glaunsinger BA (2021) A pentameric protein ring with novel architecture is required for herpesviral packaging. eLIFE 10:e62261.
  • Rizo AN, Lin J, Gates SN, Tse E, Bart SM, Castellano LM, DiMaio F, Shorter J, Southworth DR (2019) Structural basis for substrate gripping and translocation by the ClpB AAA+ disaggregase. Nature Communications 10:2393.
  • Blythe EE, Gates SN, Deshaies RH, and Martin A (2019) Multisystem Proteinopathy mutations in VCP/p97 increase NPLOC4•UFD1L binding and substrate processing. Structure 27: 1820-1829.
  • Gates SN, Martin A (2019) Stairway to translocation: AAA+ motor structures reveal the mechanisms of ATP‐dependent substrate translocation. Protein Science 29:407-419
  • Tariq A, Lin J, Jackrel ME, Hesketh CD, Carman PJ, Mack KL, Weitzman R, Gambogi C, Hernandez Murillo OA, Sweeny EA, Gurpinar E, Yokom AL, Gates SN, Yee K, Sudesh S, Stillman J, Rizo AN, Southworth DR, Shorter J (2019) Mining disaggregase sequence space to safely counter TDP-43, FUS, and α-synuclein proteotoxicity. Cell Reports 28:2080-2095.
  • de la Peña AH*, Goodall EA*, Gates SN*, Lander GC, Martin A (2018) Substrate-engaged 26Sproteasome structures reveal mechanisms for ATP-hydrolysis-driven translocation. Science 362:1018. [*co-first authors]
  • Gates SN*, Yokom AL*, Lin J, Jackrel ME, Rizo AN, Kendsersky NM, Buell CE, Sweeny EA, Mack KL, Chuang E, Torrente MP, Su M, Shorter J, Southworth DR (2017) Ratchet-like polypeptide translocation mechanism of the AAA+ disaggregase Hsp104. Science 357:273-27 .[*co-first authors]
  • Yokom AL, Gates SN, Jackrel ME, Mack KL, Su M, Shorter J, Southworth DR (2016) Spiral architecture of the Hsp104 disaggregase reveals the basis for polypeptide translocation. Nature Structural & Molecular Biology 23:830-837.
  • Cremers CM, Knoefler D, Gates S, Martin N, Dahl JU, Lempart J, Xie L, Chapman MR, Galvan V, Southworth DR, Jakob U (2016) Polyphosphate: a conserved modifier of amyloidogenic processes. Molecular Cell 63:768-780.
  • Voth W, Schick M, Gates S, Li S, Vilardi F, Gostimskaya I, Southworth DR, Schwappach B, Jakob U (2014) The protein targeting factor Get3 functions as ATP-independent chaperone under oxidative stress conditions. Molecular Cell 56:116-127.