The Cheeseman lab seeks to define the molecular mechanisms that govern cellular processes, with a particular focus on cell division and its regulation. Our research combines cutting-edge microscopy, biochemistry, and genomics approaches to understand how cells coordinate complex events throughout the cell cycle. By integrating high-throughput screening methods with focused mechanistic studies, we aim to understand both normal cellular function and its disruption in disease states.
We develop and implement large-scale screening approaches that combine CRISPR-based gene targeting with sequencing and automated microscopy. These large-scale analyses allow us to systematically uncover the functions of understudied genes and place known genes in new biological contexts. Our targeted screening approaches focus on specific biological questions, enabling deep insights into cellular processes including cell division, quiescence, and drug sensitivity. Through this work, we aim to build comprehensive resources for the cell biology community while advancing our understanding of fundamental cellular mechanisms.
We investigate how cells regulate their gene expression programs across the cell cycle, in different cellular states, and in response to various stresses. Using a combination of transcriptomics, proteomics, and advanced imaging techniques, we aim to understand the regulatory mechanisms that govern transitions between cell states. Our research extends from fundamental cell cycle regulation to specialized states, such as meiosis, quiescence, and senescence, with implications for development and disease. We are particularly interested in understanding how different layers of regulation, from transcription and splicing to translational control and post-translational modification, coordinate to define distinct cellular states.
Through a combination of high-throughput ribosome profiling, functional genetics, and mass spectrometry, we have uncovered a diverse array of protein isoforms with distinct functions in healthy and disease states. Our work focuses on characterizing these previously hidden isoforms and understanding their roles in cellular processes and disease progression. We combine computational approaches with experimental validation to identify and characterize functionally- significant isoforms, particularly those relevant to cancer and rare human genetic disease. This research has revealed novel regulatory mechanisms and potential therapeutic targets across various disease contexts.