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Natasha Zachara, Ph.D.

Natasha Elizabeth Zachara, Ph.D.

Headshot of Natasha Zachara
  • Director, Immersive Training in the Glycosciences
  • Associate Professor of Biological Chemistry

Research Interests

Regulation of cell survival/death signaling by intracellular glycosylation; regulation of metabolic pathways that impact glycosylation; autophagy; proteomics and glycomics. ...read more

Background

Dr. Natasha Zachara is an associate professor of Biological Chemistry and Oncology at the Johns Hopkins School of Medicine. Her research focuses on identifying the molecular mechanisms by which the sugar O-GlcNAc prevents cyrotoxicity, determining how cells regulate O-GlcNAc during times of stress, and how the O-GlcNAc-mediated stress response can be harnessed to reduce tissue death. 

Dr. Zachara received her undergraduate degree in biotechnology (with honors) from Macquarie University in Sydney, Australia. Her dissertation, completed at Macquarie University, focused on developing new technologies to map and quantify site-specific changes in protein glycosylation. She completed postdoctoral studies in glycobiology at the Johns Hopkins University School of Medicine. Dr. Zachara joined the Johns Hopkins faculty in 2007.

Dr. Zachara serves as the director of the K12 training program Immersive Training in the Glycosciences. She is a member of several professional organizations, including the American Society of Biochemists and Molecular Biologists, and serves on the editorial board of the Journal of Biological Chemistry. Her work has been recognized with numerous awards and honors, including the Lorne Protein Structure and Function Young Scientist Award in 2006.

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Titles

  • Director, Immersive Training in the Glycosciences
  • Associate Professor of Biological Chemistry
  • Associate Professor of Oncology

Departments / Divisions

Centers & Institutes

Education

Degrees

  • B.Tech.; Macquarie University (Australia) (1993)
  • Ph.D.; Macquarie University (Australia) (1999)

Additional Training

Honors Degree (First Class), Macquarie University (Australia) / Biotechnology (1994)

Post-doctoral studies, Johns Hopkins University School of Medicine, Baltimore, MD, 2005

Research & Publications

Research Summary

Dr. Zachara and her team are engaged in understanding which proteins are modified dynamically by O-GlcNAc in response to stress, and how this alters protein function in such a way that elevating O-GlcNAc before, or immediately after, cellular injury is protective in both in vitro and in vivo models.

In response to multiple forms of cellular stress, levels of the O-linked β-N-acetylglucosamine (O-GlcNAc) protein modification are elevated rapidly and dynamically on myriad nuclear, mitocohdrial and cytoplasmic proteins. Several studies demonstrate that elevation of O-GlcNAc prior to heat stress, oxidative stress, hypoxia, trauma hemorrhage and ischemia reperfusion injury is protective, suggesting that increased O-GlcNAc in response to stress is a survival response of cells injury. However, the mechanisms by which O-GlcNAc regulates protein function leading to cell survival have not been defined.

Dr. Zachara's long-term goal is to determine how stress-induced changes in the O-GlcNAc protein modification lead to increased cell/tissue survival in response to injury, in order to develop novel strategies for the treatment of numerous diseases, including ischemia reperfusion injury.

Lab

Lab Website: Zachara Lab

Selected Publications

Martinez M, Renuse S, Kreimer S, O'Meally R, Natov P, Madugundu AK, Nirujogi RS, Tahir R, Cole R, Pandey A, Zachara NE. Quantitative Proteomics Reveals that the OGT Interactome is Remodeled in Response to Oxidative Stress. Mol Cell Proteomics. 2021 Mar 11:100069. doi: 10.1016/j.mcpro.2021.100069. Epub ahead of print. PMID: 33716169

Taparra K, Wang H, Malek R, Lafargue A, Barbhuiya MA, Wang X, Simons BW, Ballew M, Nugent K, Groves J, Williams RD, Shiraishi T, Verdone J, Yildirir G, Henry R, Zhang B, Wong J, Wang KK, Nelkin BD, Pienta KJ, Felsher D, Zachara NE, Tran PT. O-GlcNAcylation is required for mutant KRAS-induced lung tumorigenesis. J Clin Invest. 2018 Nov 1;128(11):4924-4937. doi: 10.1172/JCI94844. Epub 2018 Sep 24. PMID: 30130254; PMCID: PMC6205381

Groves JA, Maduka AO, O'Meally RN, Cole RN, Zachara NE. Fatty acid synthase inhibits the O-GlcNAcase during oxidative stress. J Biol Chem. 2017 Apr 21;292(16):6493-6511. doi: 10.1074/jbc.M116.760785. Epub 2017 Feb 23. PMID: 28232487; PMCID: PMC5399103

Lee A, Miller D, Henry R, Paruchuri VD, O'Meally RN, Boronina T, Cole RN, Zachara NE. Combined Antibody/Lectin Enrichment Identifies Extensive Changes in the O-GlcNAc Sub-proteome upon Oxidative Stress. J Proteome Res. 2016 Dec 2;15(12):4318-4336. doi: 10.1021/acs.jproteome.6b00369. Epub 2016 Oct 14. PMID: 27669760

Kazemi Z., Chang H., Haserodt S. K., McKen C., Zachara N.E.  (2010) O-GlcNAc Regulates Stress-Induced Heat Shock Protein Expression in a GSK-3 Dependent Manner. J. Biol. Chem., 285, 39096-39107

Academic Affiliations & Courses

Graduate Program Affiliation

Graduate Program in Biological Chemistry

BCMB Graduate Program

Courses and Syllabi

  • Current Topics in Biological Chemistry
    Johns Hopkins University
    2007
  • Introduction to Glycobiology (330.712)
    Johns Hopkins University
    2012
  • Fundamental in Glycobiology (340.709)
    Johns Hopkins University
    2012
  • Techniques in Glycobiology (240.710)
    Johns Hopkins University
    2013
  • Macromolecular Structure and Analysis
    Johns Hopkins Unibersity
    2017
  • Scientific Foundations in Metabolism
    Johns Hopkins University
    2018

Activities & Honors

Honors

  • Most Cited Articles 2006 - 2010, Biochimica et Biophysica Acta (BBA), 2011
  • Top 3 Downloaded Papers of General Subjects in 2005, Biochimica et Biophysica Acta (BBA), 2006
  • Albert Lehninger Young Scientist Award, 2005
  • Lorne Protein Structure and Function Young Scientist Award, 2006
  • Young Scientist Award, International Glycoconjugate Organization, 1997
  • Australian Post-Graduate Award, Macquarie University, 1995 - 1998
  • AMRAD Molecular Biology Award, Macquarie University, 1993

Memberships

  • Cell Stress Society International, 2010
  • The American Society of Biochemists and Molecular Biologists, 2005
  • The Society for Glycobiology, 2005

Professional Activities

  • Faculty Senate (previously the Medical School Council) - Johns Hopkins School of Medicine, 2011 - 2014
  • Organizer, Glycobiology Interest Group, 2010 - 2018
  • Admissions Committee - BCMB Graduate Program, 2011 - 2018
  • Organizer, Annual Posters Session - Glycobiology Interest Group, 2012 - 2018
  • Co-Director - Biological Chemistry Graduate Program, 2012 - 2019
  • Editorial board, Journal of Biological Chemistry, 2013 - 2023
  • Director, Society for Glycobiology
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