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Debra Eckert

Debra Eckert, PhD

Languages spoken: English

Academic Information

Departments Primary - Biochemistry

Academic Office Information

deckert@biochem.utah.edu

Research Interests

  • Virology
  • Drug Design
  • Drug Resistance, Viral
  • HIV/AIDS
  • Respiratory Syncytial Viruses
  • Ebola-like Viruses
  • Biophysics
  • Ultracentrifugation
  • Surface Plasmon Resonance

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

Doctoral Training Massachusetts Institute of Technology
PhD
Texas Christian University
BS

Selected Publications

Journal Article

  1. 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 SC (2022). Homogeneous surrogate virus neutralization assay to rapidly assess neutralization activity of anti-SARS-CoV-2 antibodies. Nat Commun, 13(1), 3716.
  2. 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.
  3. 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 VA (2020). A Sec14-like phosphatidylinositol transfer protein paralog defines a novel class of heme-binding proteins. Elife, 9.
  4. Fulcher JM, Petersen ME, Giesler RJ, Cruz ZS, Eckert DM, Francis JN, Kawamoto EM, Jacobsen MT, Kay MS (2019). Chemical synthesis of Shiga toxin subunit B using a next-generation traceless "helping hand" solubilizing tag. Org Biomol Chem, 17(48), 10237-10244.
  5. 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.
  6. Safran SA, Eckert DM, Leslie EA, Bass BL (2019). PKR activation by noncanonical ligands: a 5'-triphosphate requirement versus antisense contamination. RNA, 25(9), 1192-1201.
  7. Redman JS, Francis JN, Marquardt R, Papac D, Mueller AL, Eckert DM, Welch BD, Kay MS (2018). Pharmacokinetic and Chemical Synthesis Optimization of a Potent d-Peptide HIV Entry Inhibitor Suitable for Extended-Release Delivery. Mol Pharm, 15(3), 1169-1179.
  8. Trettin KD, Sinha NK, Eckert DM, Apple SE, Bass BL (2017). Loquacious-PD facilitates Drosophila Dicer-2 cleavage through interactions with the helicase domain and dsRNA. Proc Natl Acad Sci U S A, 114(38), E7939-E7948.
  9. 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.
  10. 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.
  11. Pang HB, Hevroni L, Kol N, Eckert DM, Tsvitov M, Kay MS, Rousso I (2013). Virion stiffness regulates immature HIV-1 entry. Retrovirology, 10, 4.
  12. Francis JN, Redman JS, Eckert DM, Kay MS (2012). Design of a modular tetrameric scaffold for the synthesis of membrane-localized D-peptide inhibitors of HIV-1 entry. Bioconjug Chem, 23(6), 1252-8.
  13. Welch BD, Francis JN, Redman JS, Paul S, Weinstock MT, Reeves JD, Lie YS, Whitby FG, Eckert DM, Hill CP, Root MJ, Kay MS (2010). Design of a potent D-peptide HIV-1 entry inhibitor with a strong barrier to resistance. J Virol, 84(21), 11235-44.
  14. Eckert DM, Shi Y, Kim S, Welch BD, Kang E, Poff ES, Kay MS (2008). Characterization of the steric defense of the HIV-1 gp41 N-trimer region. Protein Sci, 17(12), 2091-100.
  15. 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 A (2005). A human monoclonal antibody neutralizes diverse HIV-1 isolates by binding a critical gp41 epitope. Proc Natl Acad Sci U S A, 102(41), 14759-64.
  16. Eckert DM, Kim PS (2001). Design of potent inhibitors of HIV-1 entry from the gp41 N-peptide region. Proc Natl Acad Sci U S A, 98(20), 11187-92.
  17. Eckert DM, Malashkevich VN, Hong LH, Carr PA, Kim PS (1999). Inhibiting HIV-1 entry: discovery of D-peptide inhibitors that target the gp41 coiled-coil pocket. Cell, 99(1), 103-15.

Review

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

Patent

  1. Welch, BD, Kay, MS, Eckert, DM, McKinnon, R., Jacobsen, M.T (2016). Compositions and Methods Related to Inhibition of Respiratory Syncytial Virus Entry. U.S. Patent No. 10,765,754. Washington, D.C.:U.S. Patent and Trademark Office.
  2. Clinton TR, Weinstock MT, Jacobsen MT, Welch BD, Eckert, DM, Kay, MS (2015). Ebolavirus Prehairpin Intermediate Mimics and Methods of Use. U.S. Patent No. 10,189,878. Washington, D.C.:U.S. Patent and Trademark Office.
  3. Eckert DM, Chan DC, Malashkevich VM, Carr PA, Kim PS (2011). Inhibitors of HIV Membrane Fusion. U.S. Patent No. 7,960,504. Washington, D.C.:U.S. Patent and Trademark Office.
  4. Eckert DM, Suntoke TR, Kim PS (2010). Soluble Chimeric Peptide Inhibitors of HIV Entry Comprising an IZ Trimeric Coiled-Coil Peptide and HIV gp41 N-helix Coiled-Coil Peptide. Licensed by Merck & Co., Inc. U.S. Patent No. 7,811,578. Washington, D.C.:U.S. Patent and Trademark Office.
  5. Shiver JW, Miller MD, Geleziunas R, Hazuda DJ, Kim PS, Eckert DM, Root MJ, Lennard SN, Bianchi E (2010). Human antibodies interacting with HIV gp41. U.S. Patent No. 7,744,887. Washington, D.C.:U.S. Patent and Trademark Office.
  6. Eckert DM, Suntoke TR, Kim PS (2007). Peptide Inhibitors of HIV Entry. Licensed by Merck & Co., Inc. U.S. Patent No. 7,226,598. Washington, D.C.:U.S. Patent and Trademark Office.
  7. Eckert DM, Chan DC, Malashkevich VM, Carr PA, Kim PS (2005). Inhibitors of HIV Membrane Fusion. Licensed by Merck & Co., Inc. and Boehringer Ingelheim International Gmbh. U.S. Patent No. 6,841,657. Washington, D.C.:U.S. Patent and Trademark Office.
  8. Eckert DM, Chan DC, Malashkevich VM, Carr PA, Kim PS (2004). Inhibitors of HIV Membrane Fusion. Licensed by Merck & Co., Inc. and Boehringer Ingelheim International Gmbh. U.S. Patent No. 6,818,740. Washington, D.C.:U.S. Patent and Trademark Office.
  9. Eckert DM, Suntoke TR, Kim PS (2004). Peptide Inhibitors of HIV Entry. Licensed by Merck & Co., Inc. U.S. Patent No. 6,747,126. Washington, D.C.:U.S. Patent and Trademark Office.