Natasha E. Zachara, PhD

Professional Titles

• Director, Immersive Training in the Glycosciences

Primary Academic Title

Associate Professor of Biological Chemistry

Background

Centers and Institutes

Basic Biomedical Sciences, Institute for

Additional Academic Titles

Associate Professor of Oncology

Research Interests

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

Lab Website

Zachara Lab - Lab Website

• Elevation of O-GlcNAc levels modulates numerous pathways in a manner consistent with increased cell survival, including the expression of heat shock proteins. The Zachara Lab's goal is to understand the O-GlcNAc regulated stress response, how this can be manipulated to improve patient outcome and how this response is misregulated in disease.

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.

Selected Publications

• 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

• 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

• 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

• 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

Courses & Syllabi

• Current Topics in Biological Chemistry, Johns Hopkins University, 8/1/07
• Introduction to Glycobiology, Johns Hopkins University, 330.712, 3/1/12
• Fundamental in Glycobiology, Johns Hopkins University, 340.709, 8/1/12
• Techniques in Glycobiology, Johns Hopkins University, 240.71, 1/1/13
• Macromolecular Structure and Analysis, Johns Hopkins Unibersity, 8/1/17
• Scientific Foundations in Metabolism, Johns Hopkins University, 11/1/18

Honors

• Most Cited Articles 2006 - 2010, Biochimica et Biophysica Acta (BBA), 1/1/11
• Top 3 Downloaded Papers of General Subjects in 2005, Biochimica et Biophysica Acta (BBA), 1/1/06
• Lorne Protein Structure and Function Young Scientist Award, 1/1/06
• Albert Lehninger Young Scientist Award, 1/1/05
• Young Scientist Award, International Glycoconjugate Organization, 1/1/97
• Australian Post-Graduate Award, Macquarie University, 1/1/95
• AMRAD Molecular Biology Award, Macquarie University, 1/1/93

Graduate Program Affiliations

• Graduate Program in Biological Chemistry

  BCMB Graduate Program

Memberships

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

Professional Activities

• Annual Posters Session - Glycobiology Interest Group, Organizer, 1/1/12 - 6/30/18
• Glycobiology Interest Group, Organizer, 1/1/10 - 6/1/18
• Journal of Biological Chemistry, Editorial board, 1/1/13 - 12/30/23
• Society for Glycobiology, Director

Additional Training

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

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