Jason M. Held, Ph.D.

Assistant Professor
Internal Medicine
Oncology
Anesthesiology

Molecular Cell Biology Program
Biochemistry Program

Research Abstract:

Research Focus:
Protein posttranslational modifications (PTMs) are vital control mechanism for cellular signaling networks that alter protein conformation, function, and protein interaction partners. Our laboratory is focused on characterizing protein PTMs and has two primary objectives that bridge biological, biochemical, and chemical technologies:
1) Developing and applying quantitative proteomic workflows to characterize novel protein PTMs
2) Delineating the mechanism of functional protein PTMs that underpin normal cellular processes and regulate disease progression.

Cysteine Redox Biology:
The primary biological focus of our laboratory is elucidating the molecular mechanisms of protein redox regulation, understanding how specific proteins are tuned to respond to specific cellular redox signals, and defining distinct redox networks governing complex physiological processes that impact both normal cell function and disease. These projects use an array of chemical probes to label and enrich oxidized cysteines, quantitative proteomics, as well as biochemical and functional studies to discern regulatory mechanisms.

Proteome exploration using quantitative mass spectrometry-based proteomics
We develop and apply state-of-the-art LC-MS instrumentation, data acquisition modes, and data analysis software to comprehensively and quantitatively profile the proteomes of cells and tissues. We often utilize affinity enrichment for unbiased profiling of specific PTM networks at a global level. In addition, we are applying new LC-MS workflows to comprehensively interrogate the PTMs, expression, isoforms, and protein-protein interaction partners of key proteins that strongly influence cancer development and other diseases.

Selected Publications:

Rardin MJ, Newman JC, Held JM, Cusack MP, Sorensen DJ, Li B, Schilling B, Mooney SD, Kahn CR, Verdin E, and Gibson BW. (2013) Label-free quantitative proteomics of the lysine acetylome in liver mitochondria identifies novel substrates of SIRT3. Proceedings of the National Academy of Sciences 110(16):6601-6606.

Rardin MJ, Held JM, Gibson BW. (2013) Targeted quantitation of acetylated lysine peptides by selected reaction monitoring mass spectrometry. Methods Mol. Biol. 1077: 121-131.

Held JM, Britton DJ, Scott GK, Lee EL, Schilling B, Baldwin MA, Gibson BW, Benz CC. (2012) Ligand Binding Promotes CDK-Dependent Phosphorylation of ER-Alpha on Hinge Serine 294 but Inhibits Ligand Independent Phosphorylation of Serine 305. Molecular Cancer Research 10:1120-32. PMCID: PMC Journal-in-Process

Held JM, Schilling B, D’Souza AK, Srinivasan T, Behring J, Sorensen DJ, Benz CC, Gibson BW. (2013) Label-free quantitation and mapping of the ErbB2 tumor receptor by multi-protease digestion with data-dependent (MS1) and data-independent (MS2) acquisitions. International Journal of Proteomics 2013; 2013:791985.

Held JM and Gibson BW. (2012) Regulatory control or oxidative damage? Proteomic approaches to interrogate the role of cysteine oxidation status in biological processes. Molecular & Cellular Proteomics 11: 1-14.

Cong X, Held JM, Degiacomo F, Bonner A, Chen JM, Schilling B, Czerwieniec GA, Gibson BW, Ellerby LM. (2011) Mass spectrometric identification of novel lysine acetylation sites in huntingtin. Molecular & Cellular Proteomics 10: 1-13.

Held JM, Danielson SR, Behring JB, Atsriku C, Britton DJ, Puckett RL, Schilling B, Campisi J, Benz CC, Gibson BW. (2010) Targeted quantitation of site-specific cysteine oxidation in endogenous proteins using a differential alkylation and multiple reaction monitoring mass spectrometry approach. Molecular & Cellular Proteomics 9: 1400-1410. PMCID: PMC2938085

Marx C, Held JM, Gibson BW, Benz CC. (2010) ErbB2 trafficking and degradation associated with K48 and K63 polyubiquitination. Cancer Research 70: 3709-3717.

Atsriku* C, Britton* DJ, Held* JM, Schilling B, Scott GK, Gibson BW, Benz CC, Baldwin MA. (2009) Systematic mapping of posttranslational modifications in human estrogen receptor alpha, with emphasis on novel phosphorylation sites. Molecular & Cellular Proteomics 8:467-480. * denotes equal author contribution. PMCID: PMC2649810

Last Updated: 12/2/2014 11:05:16 AM

Oxidation levels affect the redox status of cysteines in vivo and lead to divergent cellular responses
Back To Top

Follow us: