Natasha Zachara

Associate Professor

The O-GlcNAc regulated stress response, how this can be manipulated to improve patient outcome and how this response is misregulated in disease.
410-955-7049

WBSB 408

Lab website

Research Interests:
O-GlcNAc is a glycan modification of thousands of intracellular proteins that include transcription factors, kinases, and cytoskeletal proteins. O-GlcNAc has been implicated in regulating cellular processes including protein folding and stability, localization, activity, post-translational modifications, and interactions. The cell co-ordinates these molecular events, on thousands of cellular proteins, in concert with environmental and physiological cues, to fine-tune epigenetics, transcription, translation, signal transduction, cell cycle, and metabolism. The cellular stress response is no exception: diverse forms of injury result in dynamic changes to the O-GlcNAc subproteome that promote survival. Research in the laboratory is broadly focused on answering two questions: Firstly, which proteins are dynamically O-GlcNAc modified in response to injury and how does this simple sugar modify protein function to promote cell survival. Secondly, how are the enzymes that add and remove O-GlcNAc regulated at times of injury. We address these questions using traditional biochemical and glycobiology based techniques in combination with high throughput technologies and genetic manipulation.
 
 
Selected Publications:
 
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. PMID: 27669760.
 
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. PMID: 28232487.
 
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. PMID: 30130254. * Co-corresponding authors
 
Mesubi OO, Rokita AG, Abrol N, Wu Y, Chen B, Wang Q, Granger JM, Tucker-Bartley A, Luczak ED, Murphy KR, Umapathi P, Banerjee PS, Boronina TN, Cole RN, Maier LS, Wehrens XH, Pomerantz JL, Song LS, Ahima RS, Hart GW, Zachara NE, Anderson ME. Oxidized CaMKII and O-GlcNAcylation cause increased atrial fibrillation in diabetic mice by distinct mechanisms. J Clin Invest. 2021 Jan 19;131(2):e95747. PMID: 33151911
 
Umapathi P, Mesubi OO, Banerjee PS, Abrol N, Wang Q, Luczak ED, Wu Y, Granger JM, Wei AC, Reyes Gaido OE, Florea L, Talbot CC Jr, Hart GW, Zachara NE, Anderson ME. Excessive O-GlcNAcylation Causes Heart Failure and Sudden Death. Circulation. 2021 Apr 27;143(17):1687-1703. PMID: 33593071
 
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 12;20:100069. PMID: 33716169.

Papanicolaou KN, Jung J, Ashok D, Zhang W, Modaressanavi A, Avila E, Foster DB, Zachara NE, O’Rourke B. Inhibiting O-GlcNAcylation impacts p38 and Erk1/2 signaling and perturbs cardiomyocyte hypertrophy. J Biol Chem. 2023 Mar;299(3):102907. PMID: 36642184
 
Narayanan B, Sinha P, Henry R, Reeves RA, Paolocci N, Kohr MJ, Zachara NE. Cardioprotective O-GlcNAc signaling is elevated in murine female hearts via enhanced O-GlcNAc transferase activity. J Biol Chem. 2023 Dec;299(12):105447. PMID: 37949223
 
Link to myNCBI: