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Cellular-Wide Analysis of Genomic and Therapeutic Perturbations in Hematologic Malignancies

Significant effort in cancer research has been directed towards understanding the composition of the cancer genome. This work has produced a great deal of insight into cancer biology. However, less is known about how global protein-level dynamics interface with genomic alterations and therapeutic perturbations, despite the fact that proteins are the functional units of cancer cells that carry out biological function. To attempt to bridge this knowledge gap, we use a combination of genome engineering with cellular-wide technologies: deep sequencing (RNA-seq and ribosome profiling) and quantitative mass spectrometry-based proteomics. We primarily focus on these problems in the context of blood cancers, with a particular emphasis on multiple myeloma. The goal of our laboratory is to understand the basic biology of protein-abundance regulation in cancer as well as develop new therapeutic and diagnostic strategies based on this knowledge.

In a link to Dr. Wiita's clinical work, we have also recently begun to apply our proteomic methods to the study of phenotypic effects of copy number variation in constitutional genetics. The link between genome and proteome has been largely ignored in the field of genetics but may carry major implications for diagnosis, prognosis, and therapy.

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