The post-genomic era is marked by the development of technologies which have revealed the astonishing molecular diversity of gene products. Multiple distinct protein forms, or “proteoforms“, can arise through several levels of regulation from post-transcriptional mechanisms such as alternative splicing to post-translational mechanisms such as phosphorylation and proteolytic cleavage. These levels of regulation are in delicate balance to produce the set of physiologically normal proteoforms; however, disruption of this balance leads to expression of aberrant proteoforms that can underlie disease. Hence, there is an urgent need to discover all healthy and disease-associated proteoforms so as to develop the next generation of proteoform-focused biomarkers and therapies.
The Sheynkman lab seeks to understand how proteomic variation underlies human disease. Towards this end, the lab is developing new analytical and computational frameworks to study proteoform function by integrating tools and concepts from the areas of bioanalytical chemistry, network biology, and bioinformatics. We are developing approaches to reliably discover novel disease proteoforms, assay proteoform-specific functions, and elucidate the molecular mechanisms by which proteoforms rewire cellular networks to drive disease states.