Debra Eckert

Debra Eckert, PhD

Languages spoken: English

Academic Information

Departments Adjunct - Biochemistry

Academic Office Information

deckert@biochem.utah.edu

Lab

Debra Eckert, PhD, is a Research Assistant Professor in the Department of Biochemistry at the University of Utah School of Medicine. Eckert’s research focuses on the mechanisms of enveloped virus entry with an emphasis on developing D-peptide inhibitors of viral entry through collaboration with Michael Kay, MD, PhD, Professor of Biochemistry.

As the mirror-image of naturally occurring peptides, D-peptides are not degraded by natural proteases, leading to longer in vivo half-life and reduced immunogenicity. The lab’s most advanced D-peptide viral inhibitor, chol-PIE12-trimer, targets a protein on the surface of HIV (gp41) as it initiates viral entry. Chol-PIE12-trimer potently inhibits all clinically relevant HIV strains and possesses an unparalleled barrier to resistance. Preliminary toxicology and pharmacokinetic studies show it is safe and suitable for monthly dosing with depot formulation. Ongoing animal efficacy studies will pave the way for further preclinical and clinical testing. Chol-PIE12-trimer is promising for both prevention and treatment of HIV. Eckert and Kay have extended their D-peptide discovery/design process to additional viral targets of public health concern including Ebola virus and Respiratory Syncytial Virus (RSV).

An overarching theme of Eckert’s research career has been the application of biophysical techniques to uncover structural and functional roles of key players of the viral life cycle. As the Protein Interactions Core Director for the Structural Biology Center for HIV/HOST Interactions in Trafficking and Assembly (CHEETAH), Eckert executes biophysical studies that help define the roles of host and viral proteins in the HIV-1 life cycle.

Education History

Undergraduate Texas Christian University
 BS
Doctoral Training Massachusetts Institute of Technology
 PhD

Selected Publications

Journal Article

  1. Francis JN, Redman JS, Eckert DM, Kay M (2012). Design of a modular tetrameric scaffold for the synthesis of membrane-localized D-peptide inhibitors of HIV-1 entry. Bioconjugate chemistry, 23(6), 1252-8.
  2. Eckert DM, Shi Y, Kim S, Welch BD, Kang E, Poff ES, Kay M (2008). Characterization of the steric defense of the HIV-1 gp41 N-trimer region. Protein science, 17(12), 2091-100.
  3. 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 M (2015). Design and characterization of ebolavirus GP prehairpin intermediate mimics as drug targets. Protein science, 24(4), 446-63.
  4. Eckert DM, Malashkevich VN, Hong LH, Carr PA, Kim P (1999). Inhibiting HIV-1 entry: discovery of D-peptide inhibitors that target the gp41 coiled-coil pocket. Cell, 99(1), 103-15.
  5. Monroe N, Han H, Gonciarz MD, Eckert DM, Karren MA, Whitby FG, Sundquist WI, Hill C (2014). The oligomeric state of the active Vps4 AAA ATPase. Journal of molecular biology, 426(3), 510-25.
  6. Welch BD, Francis JN, Redman JS, Paul S, Weinstock MT, Reeves JD, Lie YS, Whitby FG, Eckert DM, Hill CP, Root MJ, Kay M (2010). Design of a potent D-peptide HIV-1 entry inhibitor with a strong barrier to resistance. Journal of virology, 84(21), 11235-44.
  7. Eckert DM, Kim P (2001). Design of potent inhibitors of HIV-1 entry from the gp41 N-peptide region. Proceedings of the National Academy of Sciences of the United States of America, 98(20), 11187-92.
  8. Miller MD, Geleziunas R, Bianchi E, Lennard S, Hrin R, Zhang H, Lu M, An Z, Ingallinella P, Finotto M, Mattu M, Finnefrock AC, Bramhill D, Cook J, Eckert DM, Hampton R, Patel M, Jarantow S, Joyce J, Ciliberto G, Cortese R, Lu P, Strohl W, Schleif W, McElhaugh M, Lane S, Lloyd C, Lowe D, Osbourn J, Vaughan T, Emini E, Barbato G, Kim PS, Hazuda DJ, Shiver JW, Pessi (2005). A human monoclonal antibody neutralizes diverse HIV-1 isolates by binding a critical gp41 epitope. Proceedings of the National Academy of Sciences of the United States of America, 102(41), 14759-64.
  9. Trettin KD, Sinha NK, Eckert DM, Apple SE, Bass B (2017). Loquacious-PD facilitates Drosophila Dicer-2 cleavage through interactions with the helicase domain and dsRNA. Proceedings of the National Academy of Sciences of the United States of America, 114(38), E7939-E7948.
  10. Safran SA, Eckert DM, Leslie EA, Bass B (2019). PKR activation by noncanonical ligands: a 5'-triphosphate requirement versus antisense contamination. RNA (New York, N.Y.), 25(9), 1192-1201.
  11. Fulcher JM, Petersen ME, Giesler RJ, Cruz ZS, Eckert DM, Francis JN, Kawamoto EM, Jacobsen MT, Kay M (2019). Chemical synthesis of Shiga toxin subunit B using a next-generation traceless "helping hand" solubilizing tag. Organic & biomolecular chemistry, 17(48), 10237-10244.
  12. Redman JS, Francis JN, Marquardt R, Papac D, Mueller AL, Eckert DM, Welch BD, Kay M (2018). Pharmacokinetic and Chemical Synthesis Optimization of a Potent d-Peptide HIV Entry Inhibitor Suitable for Extended-Release Delivery. Molecular pharmaceutics, 15(3), 1169-1179.
  13. Pang HB, Hevroni L, Kol N, Eckert DM, Tsvitov M, Kay MS, Rousso (2013). Virion stiffness regulates immature HIV-1 entry. Retrovirology, 10, 4.
  14. Smith AR, Weinstock MT, Siglin AE, Whitby FG, Francis JN, Hill CP, Eckert DM, Root MJ, Kay M (2019). Characterization of resistance to a potent D-peptide HIV entry inhibitor. Retrovirology, 16(1), 28.
  15. Khan D, Lee D, Gulten G, Aggarwal A, Wofford J, Krieger I, Tripathi A, Patrick JW, Eckert DM, Laganowsky A, Sacchettini J, Lindahl P, Bankaitis V (2020). A Sec14-like phosphatidylinositol transfer protein paralog defines a novel class of heme-binding proteins. eLife, 9,
  16. Kim SJ, Yao Z, Marsh MC, Eckert DM, Kay MS, Lyakisheva A, Pasic M, Bansal A, Birnboim C, Jha P, Galipeau Y, Langlois MA, Delgado JC, Elgort MG, Campbell RA, Middleton EA, Stagljar I, Owen S (2022). Homogeneous surrogate virus neutralization assay to rapidly assess neutralization activity of anti-SARS-CoV-2 antibodies. Nature communications, 13(1), 3716.
  17. Xiong X, Blakely A, Kim JH, Menting JG, Schäfer IB, Schubert HL, Agrawal R, Gutmann T, Delaine C, Zhang YW, Artik GO, Merriman A, Eckert D, Lawrence MC, Coskun Ü, Fisher SJ, Forbes BE, Safavi-Hemami H, Hill CP, Chou D (2022). Symmetric and asymmetric receptor conformation continuum induced by a new insulin. Nature chemical biology, 18(5), 511-519.
  18. Goodell DJ, Whitby FG, Mellem JE, Lei N, Brockie PJ, Maricq AJ, Eckert DM, Hill CP, Madsen DM, Maricq A (2024). Mechanistic and structural studies reveal NRAP-1-dependent coincident activation of NMDARs. Cell reports, 43(2), 113694.
  19. Charbonneau AA, Eckert DM, Gauvin CC, Lintner NG, Lawrence C (2021). Cyclic Tetra-Adenylate (cA(4)) Recognition by Csa3; Implications for an Integrated Class 1 CRISPR-Cas Immune Response in Saccharolobus solfataricus. Biomolecules, 11(12),

Review

  1. Eckert DM, Kim PS (2001). Mechanisms of viral membrane fusion and its inhibition. [Review]. Annu Rev Biochem, 70, 777-810.