The past two decades have provided tremendous achievements in the ability to decode the genome and identify genes that are associated with disease. These capabilities allowed the medical community to classify diseases based on specific mutations and genetic signatures that taught us about the molecular basis of tumorigenesis, metastasis, and response to drugs of individual patients. Yet, both DNA sequencing and gene expression analysis report on rather indirect effects that often do not correlate with the actual activity of proteins in cells and tissues, which is largely determined by PTMs.

 

To understand the dynamic regulation of the human proteome and how PTMs affect cell regulation and function, we developed a quantitative and tractable high-throughput biochemical system which enables monitoring of multiple modifications of thousands of proteins in parallel, under conditions that are relatively close to those of the complex cellular environment. Our unique PTM profiling approach offers a novel opportunity to detect changes in PTM patterns in response to the specific signal, in disease, and across cell types. We utilize this approach in our quest to map the PTM landscape in health and disease, both in molecular and clinical settings.

 

In addition, we are developing novel technologies for immuno-proteomic analysis focused on PTM changes using our Fusion-Lumos Mass spectrometer. Our lab is also equipped with a high content imaging system, the Operetta System for rapid analysis of cellular phenotypes in response to alterations in signaling pathways, protein modifications and small molecule inhibitors.