Christopher Peter Hill

Christopher Peter Hill, DPhil

Languages spoken: English

Academic Information

Departments Primary - Biochemistry

Academic Office Information

chris@biochem.utah.edu

Research Interests

  • Insulin Receptor Ligands and Signaling
  • Protein Structure and Function
  • Structural Biology
  • Proteasome Activation and Regulation
  • Protein Quality Control
  • HIV Structure and Host Interactions
  • ESCRT Pathway
  • Nucleosome Remodeling and Reorganization

Christopher Hill (D.Phil). Vice Dean of Research for the School of Medicine. Distinguished Professor of Biochemistry. H.A. and Edna Benning Presidential Endowed Chair. Chair of the H.A. and Edna Benning Medical Society Chair. Served as department co-chair jointly with Wes Sundquist from 7/1/2009 to 12/1/2019.

The Hill Lab uses structural and biochemical approaches to study how proteins function. This approach is applied to numerous biological pathways, including HIV architecture and host interactions, ubiquitin-proteasome system, chromatin regulation, ESCRT pathway, insulin signaling, fundamental questions of biological mechanism, and the development of novel therapeutics.

Hill received his BA and D.Phil. from the University of York, England. He then completed a postdoctoral fellowship at the University of California at Los Angles. Hill presents and publishes widely and has received numerous research fellowships and grants. He is the recipient of the Dorothy Crowfoot Hodgkin Award for "exceptional contributions in protein science which profoundly influence our understanding of biology" and is an elected member of the American Academy of Arts and Sciences.

Education History

Postdoctoral Fellowship Univesity of California at Los Angeles
 Postdoctoral Fellow
University of York
 Postdoctoral Fellow
Doctoral Training University of York
 DPhil
University of York
 BA

Selected Publications

Journal Article

  1. Espino-Sanchez TJ, Wienkers H, Marvin RG, Nalder SA, Garca-Guerrero AE, VanNatta PE, Jami-Alahmadi Y, Mixon Blackwell A, Whitby FG, Wohlschlegel JA, Kieber-Emmons MT, Hill CP, Sigala PA (2023). Direct tests of cytochrome c and c(1) functions in the electron transport chain of malaria parasites. Proc Natl Acad Sci U S A, 120(19), e2301047120.
  2. Hicks KG, Cluntun AA, Schubert HL, Hackett SR, Berg JA, Leonard PG, Ajalla Aleixo MA, Zhou Y, Bott AJ, Salvatore SR, Chang F, Blevins A, Barta P, Tilley S, Leifer A, Guzman A, Arok A, Fogarty S, Winter JM, Ahn HC, Allen KN, Block S, Cardoso IA, Ding J, Dreveny I, Gasper WC, Ho Q, Matsuura A, Palladino MJ, Prajapati S, Sun P, Tittmann K, Tolan DR, Unterlass J, VanDemark AP, Vander Heiden MG, Webb BA, Yun CH, Zhao P, Wang B, Schopfer FJ, Hill CP, Nonato MC, Muller FL, Cox JE, Rutter J (2023). Protein-metabolite interactomics of carbohydrate metabolism reveal regulation of lactate dehydrogenase. Science, 379(6636), 996-1003.
  3. Xu Y, Han H, Cooney I, Guo Y, Moran NG, Zuniga NR, Price JC, Hill CP, Shen PS (2022). Active conformation of the p97-p47 unfoldase complex. Nat Commun, 13(1), 2640.
  4. Xiong X, Blakely A, Kim JH, Menting JG, Schfer IB, Schubert HL, Agrawal R, Gutmann T, Delaine C, Zhang YW, Artik GO, Merriman A, Eckert D, Lawrence MC, Coskun, Fisher SJ, Forbes BE, Safavi-Hemami H, Hill CP, Chou DH (2022). Symmetric and asymmetric receptor conformation continuum induced by a new insulin. Nat Chem Biol, 18(5), 511-519.
  5. Ramiro IBL, Bjrn-Yoshimoto WE, Imperial JS, Gajewiak J, Salcedo PF, Watkins M, Taylor D, Resager W, Ueberheide B, Bruner-Osborne H, Whitby FG, Hill CP, Martin LF, Patwardhan A, Concepcion GP, Olivera BM, Safavi-Hemami H (2022). Somatostatin venom analogs evolved by fish-hunting cone snails: From prey capture behavior to identifying drug leads. Sci Adv, 8(12), eabk1410.
  6. Connell Z, Parnell TJ, McCullough LL, Hill CP, Formosa T (2021). The interaction between the Spt6-tSH2 domain and Rpb1 affects multiple functions of RNA Polymerase II. Nucleic Acids Res, 50(2), 784-802.
  7. Song A, Hazlett Z, Abeykoon D, Dortch J, Dillon A, Curtiss J, Martinez SB, Hill CP, Yu C, Huang L, Fushman D, Cohen RE, Yao T (2021). Branched ubiquitin chain binding and deubiquitination by UCH37 facilitate proteasome clearance of stress-induced inclusions. Elife, 10.
  8. Liu L, Tang M, Pragani R, Whitby FG, Zhang YQ, Balakrishnan B, Fang Y, Karavadhi S, Tao D, LeClair CA, Hall MD, Marugan JJ, Boxer M, Shen M, Hill CP, Lai K, Patnaik S (2021). Structure-Based Optimization of Small Molecule Human Galactokinase Inhibitors. J Med Chem, 64, 13551-13571.
  9. Kessler JL, Kang G, Qin Z, Kang H, Whitby FG, Cheatham TE 3rd, Hill CP, Li Y, Yu SM (2021). Peptoid Residues Make Diverse, Hyperstable Collagen Triple-Helices. J Am Chem Soc, 143(29), 10910-10919.
  10. Zheng Y, Schubert HL, Singh PK, Martins LJ, Engelman AN, DOrso I, Hill CP, Planelles V (2021). Cleavage and Polyadenylation Specificity Factor 6 Is Required for Efficient HIV-1 Latency Reversal. mBio, 12(3), e0109821.
  11. Sarabia I, Novis CL, Macedo AB, Takata H, Nell R, Kakazu JC, Furler RL, Shakya B, Schubert HL, Hill CP, DePaula-Silva AB, Spivak AM, Trautmann L, Planelles V, Bosque A (2021). Activation of the Anti-Oxidative Stress Response Reactivates Latent HIV-1 Through the Mitochondrial Antiviral Signaling Protein Isoform MiniMAVS. Front Immunol, 12, 682182.
  12. Han H, Schubert HL, McCullough J, Monroe N, Purdy MD, Yeager M, Sundquist WI, Hill CP (2019). Structure of spastin bound to a glutamate-rich peptide implies a hand-over-hand mechanism of substrate translocation. J Biol Chem, 295(2), 435-443.
  13. Xiong X, Blakely A, Karra P, VandenBerg MA, Ghabash G, Whitby F, Zhang YW, Webber MJ, Holland WL, Hill CP, Chou DH (2019). Novel four-disulfide insulin analog with high aggregation stability and potency. Chem Sci, 11(1), 195-200.
  14. Smith AR, Weinstock MT, Siglin AE, Whitby FG, Francis JN, Hill CP, Eckert DM, Root MJ, Kay MS (2019). Characterization of resistance to a potent D-peptide HIV entry inhibitor. Retrovirology, 16(1), 28.
  15. Cooney I, Han H, Stewart MG, Carson RH, Hansen DT, Iwasa JH, Price JC, Hill CP, Shen PS (2019). Structure of the Cdc48 segregase in the act of unfolding an authentic substrate. Science, 365(6452), 502-505.
  16. Chun Y, Joo YJ, Suh H, Batot G, Hill CP, Formosa T, Buratowski S (2019). Selective Kinase Inhibition Shows That Bur1 (Cdk9) Phosphorylates the Rpb1 Linker In Vivo. Mol Cell Biol, 39(15).
  17. Hemmis CW, Heard SC, Hill CP (2019). Phosphorylation of Tyr-950 in the proteasome scaffolding protein RPN2 modulates its interaction with the ubiquitin receptor RPN13. J Biol Chem, 294(25), 9659-9665.
  18. Han H, Fulcher JM, Dandey VP, Iwasa JH, Sundquist WI, Kay MS, Shen PS, Hill CP (2019). Structure of Vps4 with circular peptides and implications for translocation of two polypeptide chains by AAA+ ATPases. Elife, 8.
  19. Zurita Rendn O, Fredrickson EK, Howard CJ, Van Vranken J, Fogarty S, Tolley ND, Kalia R, Osuna BA, Shen PS, Hill CP, Frost A, Rutter J (2018). Vms1p is a release factor for the ribosome-associated quality control complex. Nat Commun, 9(1), 2197.
  20. Han H, Monroe N, Sundquist WI, Shen PS, Hill CP (2017). The AAA ATPase Vps4 binds ESCRT-III substrates through a repeating array of dipeptide-binding pockets. Elife, 6.
  21. Nielson JR, Fredrickson EK, Waller TC, Rendn OZ, Schubert HL, Lin Z, Hill CP, Rutter J (2017). Sterol Oxidation Mediates Stress-Responsive Vms1 Translocation to Mitochondria. Mol Cell, 68(4), 673-685.e6.
  22. Sdano MA, Fulcher JM, Palani S, Chandrasekharan MB, Parnell TJ, Whitby FG, Formosa T, Hill CP (2017). A novel SH2 recognition mechanism recruits Spt6 to the doubly phosphorylated RNA polymerase II linker at sites of transcription. Elife, 6.
  23. VanderLinden RT, Hemmis CW, Yao T, Robinson H, Hill CP (2017). Structure and energetics of pairwise interactions between proteasome subunits RPN2, RPN13, and ubiquitin clarify a substrate recruitment mechanism. J Biol Chem, 292(23), 9493-9504.
  24. Monroe N, Han H, Shen PS, Sundquist WI, Hill CP (2017). Structural basis of protein translocation by the Vps4-Vta1 AAA ATPase. Elife, 6.
  25. VanderLinden RT, Hemmis CW, Schmitt B, Ndoja A, Whitby FG, Robinson H, Cohen RE, Yao T, Hill CP (2016). Structural Basis for the Activation and Inhibition of the UCH37 Deubiquitylase. Mol Cell, 61(3), 487.
  26. Kemble DJ, McCullough LL, Whitby FG, Formosa T, Hill CP (2015). FACT Disrupts Nucleosome Structure by Binding H2A-H2B with Conserved Peptide Motifs. Mol Cell, 60(2), 294-306.
  27. Han H, Monroe N, Votteler J, Shakya B, Sundquist WI, Hill CP (2015). Binding of Substrates to the Central Pore of the Vps4 ATPase Is Autoinhibited by the Microtubule Interacting and Trafficking (MIT) Domain and Activated by MIT Interacting Motifs (MIMs). J Biol Chem, 290(21), 13490-9.
  28. Clinton TR, Weinstock MT, Jacobsen MT, Szabo-Fresnais N, Pandya MJ, Whitby FG, Herbert AS, Prugar LI, McKinnon R, Hill CP, Welch BD, Dye JM, Eckert DM, Kay MS (2015). Design and characterization of ebolavirus GP prehairpin intermediate mimics as drug targets. Protein Sci, 24(4), 446-63.
  29. Vander Linden RT, Hemmis CW, Schmitt B, Ndoja A, Whitby FG, Robinson H, Cohen RE, Yao T, Hill CP (2015). Structural basis for the activation and inhibition of the UCH37 deubiquitylase. Mol Cell, 57(5), 901-911.
  30. Monroe N, Han H, Gonciarz MD, Eckert DM, Karren MA, Whitby FG, Sundquist WI, Hill CP (2014). The oligomeric state of the active Vps4 AAA ATPase. J Mol Biol, 426(3), 510-25.
  31. Kemble DJ, Whitby FG, Robinson H, McCullough LL, Formosa T, Hill CP (2013). Structure of the Spt16 middle domain reveals functional features of the histone chaperone FACT. J Biol Chem, 288(15), 10188-94.
  32. Schubert HL, Wittmeyer J, Kasten MM, Hinata K, Rawling DC, Hroux A, Cairns BR, Hill CP (2013). Structure of an actin-related subcomplex of the SWI/SNF chromatin remodeler. Proc Natl Acad Sci U S A, 110(9), 3345-50.
  33. Stadtmueller BM, Kish-Trier E, Ferrell K, Petersen CN, Robinson H, Myszka DG, Eckert DM, Formosa T, Hill CP (2012). Structure of a proteasome Pba1-Pba2 complex: implications for proteasome assembly, activation, and biological function. J Biol Chem, 287(44), 37371-82.
  34. Tian G, Park S, Lee MJ, Huck B, McAllister F, Hill CP, Gygi SP, Finley D (2011). An asymmetric interface between the regulatory and core particles of the proteasome. Nat Struct Mol Biol, 18(11), 1259-67.
  35. Zhai Q, Landesman MB, Chung HY, Dierkers A, Jeffries CM, Trewhella J, Hill CP, Sundquist WI (2011). Activation of the retroviral budding factor ALIX. J Virol, 85(17), 9222-6.
  36. Zhang H, Constantine R, Vorobiev S, Chen Y, Seetharaman J, Huang YJ, Xiao R, Montelione GT, Gerstner CD, Davis MW, Inana G, Whitby FG, Jorgensen EM, Hill CP, Tong L, Baehr W (2011). UNC119 is required for G protein trafficking in sensory neurons. Nat Neurosci, 14(7), 874-80.
  37. Zhang H, Constantine R, Vorobiev S, Chen Y, Seetharaman J, Huang YJ, Xiao R, Montelione GT, Gerstner CD, Davis MW, Inana G, Whitby FG, Jorgensen EM, Hill CP, Tong L, Baehr W (2011). UNC119 is required for G protein trafficking in sensory neurons. Nat Neurosci, 14(7), 874-80.
  38. Close D, Johnson SJ, Sdano MA, McDonald SM, Robinson H, Formosa T, Hill CP (2011). Crystal structures of the S. cerevisiae Spt6 core and C-terminal tandem SH2 domain. J Mol Biol, 408(4), 697-713.
  39. Zhai Q, Landesman MB, Robinson H, Sundquist WI, Hill CP (2011). Identification and structural characterization of the ALIX-binding late domains of simian immunodeficiency virus SIVmac239 and SIVagmTan-1. J Virol, 85(1), 632-7.
  40. Zhai Q, Landesman MB, Robinson H, Sundquist WI, Hill CP (2011). Structure of the Bro1 domain protein BROX and functional analyses of the ALIX Bro1 domain in HIV-1 budding. PLoS One, 6(12), e27466.

Review

  1. Tsai FTF, Hill CP (2020). Same structure, different mechanisms? [Review]. Elife, 9.
  2. Han H, Hill CP (2019). Structure and mechanism of the ESCRT pathway AAA+ ATPase Vps4. [Review]. Biochem Soc Trans, 47(1), 37-45.
  3. Monroe N, Hill CP (2015). Meiotic Clade AAA ATPases: Protein Polymer Disassembly Machines. [Review]. J Mol Biol, 428(9 Pt B), 1897-911.
  4. Hill CP, Sundquist WI (2013). Building a super elongation complex for HIV. [Review]. Elife, 2, e00577.
  5. Kish-Trier E, Hill CP (2013). Structural biology of the proteasome. [Review]. Annu Rev Biophys, 42, 29-49.
  6. Hill CP, Babst M (2012). Structure and function of the membrane deformation AAA ATPase Vps4. [Review]. Biochim Biophys Acta, 1823(1), 172-81.
  7. Stadtmueller BM, Hill CP (2011). Proteasome activators. [Review]. Mol Cell, 41(1), 8-19.

Editorial

  1. Forest KT, Hill CP (2015). Editorial overview: Macromolecular machines and assemblies: Rise and fall at the molecular level. Curr Opin Struct Biol, 31, vii-viii.