Dr. Keith Vosseller
Visiting Assistant Professor of Biology
Office: Parente 110
Phone: 570-208-5726
email: keithvosseller@kings.edu
Educational Background
B.A. Biology, Miami University (Ohio).
Ph.D. Molecular Biology, Cornell
Post-doctoral fellowship, Johns Hopkins; Novel cytoplasmic glycosylation of proteins in signal transduction.
Courses Taught
- BIOL 213 Cell and Molecular Biology
- BIOL 224 Biochemistry for Medical Studies
Research Interests
We're interested in a novel type of post-translational modification of proteins called O-GlcNAc (N-acetyl-glucosamine). Unlike all other known types of glycosylation, O-GlcNAc modifies serines and threonines of cytosolic proteins to functionally regulate their activity in signal transduction pathways. We are interested in understanding both fundamental mechanisms of how dynamic O-GlcNAc alters protein function and how aberrant levels of O-GlcNAc are linked to pathologies in disease states such as Cancer and Alzheimer's. In this context, the enzymes which catalyze addition and removal of O-GlcNAc may be novel therapeutic drug targets.
Selected Publications
Ma Z, Chalkley RJ, Vosseller K. Hyper-O-GlcNAcylation activates nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) signaling through interplay with phosphorylation and acetylation. J Biol Chem. 2017 Jun 2;292(22):9150-9163.
Ma Z, Vosseller K. Cancer Metabolism and Elevated O-GlcNAc in Oncogenic Signaling. J Biol Chem. 2014 Dec 12;289(50):34457-34465.
Skorobogatko Y, Landicho A, Chalkley RJ, Kossenkov AV, Gallo G, Vosseller K.
O-GlcNAc site Thr87 regulates synapsin I localization to synapses and size of the reserve pool of synaptic vesicles. J Biol Chem. 2014 Feb 7;289(6):3602-12.
Ma Z, Vosseller K. O-GlcNAc in cancer biology. Amino Acids. 2013
Oct;45(4):719-33. doi: 10.1007/s00726-013-1543-8.
Ma Z, Vocadlo DJ, Vosseller K. Hyper-O-GlcNAcylation is anti-apoptotic and maintains constitutive NF-κB activity in pancreatic cancer cells. J Biol Chem. 2013 May 24;288(21):15121-30.
Ma ZY, Skorobogatko Y, Vosseller K. Tandem lectin weak affinity chromatography for glycoprotein enrichment. Methods Mol Biol. 2013;951:21-31.
Yuzwa, S.A., Shan, X., Macauley, M.S., Skorobogatko, Y., Vosseller, K., and Vocadlo, D.J. Glycosylation attenuates tau aggregation and slows neurodegeneration in a tauopathy mouse model. Nature Chemical Biology, 2012 Feb 26;8(4):393-9.
Lynch TP, Ferrer CM, Jackson SR, Shahriari KS, Vosseller K, Reginato MJ. Critical role of O-Linked β-N-acetylglucosamine transferase in prostate cancer invasion, angiogenesis, and metastasis. J Biol Chem. 2012 Mar 30;287(14):11070-81.
Yuzwa SA, Shan X, Macauley MS, Clark T, Skorobogatko Y, Vosseller K, Vocadlo DJ. Increasing O-GlcNAc slows neurodegeneration and stabilizes tau against aggregation. Nat Chem Biol. 2012 Feb 26;8(4):393-9.
Zachara, N.E., Vosseller, K., Hart, G.W. Detection and analysis of proteins modified by o-linked N-acetylglucosamine. Curr Protoc Protein Sci., Chapter 12: Unit 12.8. PubMed PMID: 22045558, 2011.
Zachara, N.E., Vosseller, K., Hart, G.W. Detection and analysis of proteins modified by O-linked N-acetylglucosamine. Curr Protoc Mol Biol., Chapter 17: Unit 17.6. PubMed PMID: 21732316, 2011.
Yuzwa, S.A., Yadav, A.K., Skorobogatko, Y., Clark, T., Vosseller, K., Vocadlo, D.J. Mapping O-GlcNAc modification sites on tau and generation of a site-specific O-GlcNAc tau antibody. Amino Acids; 40(3):857-68. 2011
Skorobogatko, Y.V., Deuso, J., Adolf-Bryfogle, J., Nowak, M.G., Gong, Y., Lippa, C.F., Vosseller, K. Human Alzheimer's disease synaptic O-GlcNAc site mapping and iTRAQ expression proteomics with ion trap mass spectrometry. Amino Acids, 40(3):765-79. Epub 2010 Jun 19. PubMed PMID: 20563614, 2010.
Caldwell, S.A., Jackson, S.R., Shahriari, K.S., Lynch, T.P., Sethi, G., Walker, S., Vosseller, K., Reginato, M.J. Nutrient sensor O-GlcNAc transferase regulates breast cancer tumorigenesis through targeting of the oncogenic transcription factor FoxM1. Oncogene, 29(19):2831-42. 2010
Francisco, H., Kollins, K., Varghis, N., Vocadlo, D., Vosseller, K., Gallo, G. O-GLcNAc post-translational modifications regulate the entry of neurons into an axon branching program. Dev Neurobiol., 69(2-3):162-73. 2009
Tallent, M.K., Varghis, N., Skorobogatko, Y., Hernandez-Cuebas, L., Whelan, K., Vocadlo, D.J., Vosseller, K. In vivo modulation of O-GlcNAc levels regulates hippocampal synaptic plasticity through interplay with phosphorylation. J Biol Chem., 284(1):174-81. 2009
Savage, P.A., Vosseller, K., Kang, C., Larimore, K., Riedel, E., Wojnoonski, K., Jungbluth, A.A., Allison, J.P. Recognition of a ubiquitous self-antigen by prostate cancer-infiltrating CD8+ T lymphocytes. Science, 319(5860):215-20. 2008
Vosseller, K. Proteomics of Alzheimer's disease: Unveiling protein dysregulation in complex neuronal systems. Proteomics Clin Appl., (11):1351-61. 2007
Vosseller, K., Trinidad, J.C, Chalkley, R.J., Specht, C.G., Thalhammer, A., Lynn, A.J., Snedecor, J.O., Guan, S., Medzihradszky, K.F., Maltby, D.A., Schoepfer, R., Burlingame, A.L. O-linked N-acetylglucosamine proteomics of postsynaptic density preparations using lectin weak affinity chromatography and mass spectrometry. Mol Cell Proteomics, 5(5):923-34. 2006
Slawson, C., Zachara, N.E., Vosseller, K., Cheung, W.D., Lane, M.D., Hart, G.W. Perturbations in O-linked beta-N-acetylglucosamine protein modification cause severe defects in mitotic progression and cytokinesis. J Biol Chem., 280(38):32944-56. 2005
Vosseller, K., Hansen, K.C., Chalkley, R.J., Trinidad, J.C., Wells, L., Hart, G.W., Burlingame, A.L. Quantitative analysis of both protein expression and serine/threonine post-translational modifications through stable isotope labeling with dithiothreitol. Proteomics, 5(2):388-98. 2005
Wells, L., Vosseller, K., Hart, G.W. A role for N-acetylglucosamine as a nutrient sensor and mediator of insulin resistance. Cell Mol Life Sci., (2):222-8. Review. 2003.
Vosseller, K., Sakabe, K., Wells, L., Hart, G.W. Diverse regulation of protein function by O-GlcNAc: a nuclear and cytoplasmic carbohydrate post-translational modification. Curr Opin Chem Biol., (6):851-7. Review. PubMed PMID:12470741, 2002.
Wells, L., Vosseller, K., Cole, R.N., Cronshaw, J.M., Matunis, M.J., Hart, G.W. Mapping sites of O-GlcNAc modification using affinity tags for serine and threonine post-translational modifications. Mol Cell Proteomics, 1(10):791-804, 2002.
Vosseller, K., Wells, L., Lane, M.D., Hart, G.W. Elevated nucleocytoplasmic glycosylation by O-GlcNAc results in insulin resistance associated with defects in Akt activation in 3T3-L1 adipocytes. Proc Natl Acad Sci U S A, 99(8):5313-8. 2002.
Wells, L., Gao, Y., Mahoney, J.A., Vosseller, K., Chen, C., Rosen, A., Hart, G.W. Dynamic O-glycosylation of nuclear and cytosolic proteins: further characterization of the nucleocytoplasmic beta-N-acetylglucosaminidase, O-GlcNAcase. 2002.
Vosseller, K., Wells, L., Hart, G.W. Nucleocytoplasmic O-glycosylation: O-GlcNAc and functional proteomics. Biochimie., 83(7):575-81. 2001.
Comer, F.I.,Vosseller, K., Wells, L., Accavitti, M.A., Hart, G.W. Characterization of a mouse monoclonal antibody specific for O-linked N-acetylglucosamine. 2001.
Wells, L., Vosseller, K., Hart, G.W. Glycosylation of nucleocytoplasmic proteins: signal transduction and O-GlcNAc. Science, 291(5512):2376-8. 2001.