Faculty
Jason Held.jpg

Jason M. Held, PhD

Assistant Professor
Department of Medicine
Oncology Division
Molecular Oncology
Anesthesiology

Research Interests

  • Redox signaling
  • Proteomics
  • Lung cancer
  • Protein post-translational modifications

Contact

  • 314-747-9738 (office)
  • 314-747-0571 (lab)
  • 314-747-9320 (fax)
  • Division of Oncology
    Campus Box 8069
    Washington University School of Medicine
    660 South Euclid Avenue
    St. Louis, MO 63110
  • Lab website
  • DBBS profile

Research

Research focus

Protein post-translational modifications (PTMs) are vital control mechanisms 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:

  • Developing and applying quantitative proteomic workflows to characterize novel protein PTMs
  • 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.

 

Redox status of cysteines

Legend: Oxidation levels affect the redox status of cysteines in vivo and lead to divergent cellular responses. A) The redox continuum of oxidation in the cell ranges from reductive stress to oxidative stress with low levels of oxidation present in unstressed cells. B) Cysteines can be oxidized to different states depending on the oxidation level in the cell. C) While cysteine oxoforms essential to cell survival and proliferation (yellow) are the primary type of cysteine modification found in unstressed cells, a moderate increase in oxidation may lead to an adaptive response such as glutathionylation (S-GSH) of cysteines. Severe oxidative stress leads to senescence or cell death and is accompanied by overoxidized cysteine oxoforms such as sulfinic (orange) and sulfonic acid (red) which are dysfunctional. Hypoxia and reductive stress disrupts essential redox reactions (red X) and can result in cell death.

 

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.