Proteomics and cancer cell signaling

Proteins are fundamental, functional unit of cells and are drug targets in treating disease, esp cancer. However clinical decision for treating tumor is largely not based on proteome expression of tumors. This is partly due to lack of deep proteome profiles of many tumor entities. With the advent of highly sensitive mass spectrometry and high throughput sample preparation workflow we position our lab to comprehensive characterize the proteomic landscape of tumors and integrate with genomic and clinical data, a multiomic approach to uncover protein targets for treating cancer entities.  

In general, cancer has been viewed as a process governed by genetic mechanisms. However, is becoming more and more clear that non-genetic mechanisms may play an equally important role in cancer and its evolution. Particularly non-genetic events can lead to a variety of phenotypic states with distinct functional characteristics. These events have a crucial impact on cancer growth, progression, and response to drug treatment. Understanding the non-genetic molecular basis orchestrating the establishment and maintenance of such phenotypic states, particularly under treatment conditions may provide a tool to selectively direct the development of cancer cell populations towards less aggressive drug sensitive phenotypes. We utilize mass spectrometry-based proteomics to uncover the post-translational events governing the drug resistant state. 

To define cellular phenotype and resolving heterogeneity at proteome level in an unbiased way will be more informative and powerful for interrogating the heterogeneity of biological functional states. Deciphering cancer cell heterogeneity with spatial, temporal, and functional resolution is crucial, particularly for establishing efficient therapy that targets all tumor subclones. In our lab we focus on developing, and applying the single cell proteomic approach to understand heterogeneity, dynamics and response to drug treatment, signaling and tumor cell fitness. 

Drug resistance in cancer continues to be one of the principle limiting factors in achieving cure, and a major impediment to patient survival. We recently discovered that mRNA splicing factors plays a key role in mediating drug response in cancer cells. We showed (non-mutated)-splicing factor regulation by phosphorylation could alter the response to targeted therapy in cancer. How splicing factors as a class are post-translationally regulated by signaling pathways remains unknown, and this understanding may reveal novel mechanisms and therapeutic opportunities. Thus, the mechanism of mRNA splicing factors regulation in the context of various cancer relevant mutations and in different cancer entities, in particular hematological malignancies is one of the major focus of our work.