Research

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.

Biological Discovery Through Large-Scale Functional Genomics Screens

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.

Large-scale optical screening

Recent Publications

Functional genetics reveals modulators of antimicrotubule drug sensitivity
Su KC, Radul E, Maier NK, Tsang MJ, Goul C, Moodie B, Marescal O, Keys HR, Cheeseman IM
Journal of Cell Biology (2025)
The phenotypic landscape of essential human genes
Funk L, Su KC, Ly J, Feldman D, Singh A, Moodie B, Blainey PC, Cheeseman IM
Cell (2022)

Control of Gene Expression in Different Cell States

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.

Recent Publications

A conserved germline-specific Dsn1 alternative splice isoform supports oocyte and embryo development
Ly J, Blengini CS, Cady SL, Schindler K, Cheeseman IM
Current Biology (2024)
Cellular Mechanisms and Regulation of Quiescence
Marescal O, Cheeseman IM
Developmental Cell (2020)
Quiescent Cells Actively Replenish CENP-A Nucleosomes to Maintain Centromere Identity and Proliferative Potential
Swartz SZ, McKay LS, Su KC, Bury L, Padeganeh A, Maddox PS, Knouse KA, Cheeseman IM
Developmental Cell (2019)
Gene expression analysis

Protein Isoforms in Cell Biology and Disease

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.

Protein isoform analysis

Recent Publications

Nuclear release of eIF1 restricts start-codon selection during mitosis
Ly J, Xiang K, Su KC, Sissoko GB, Bartel DP, Cheeseman IM
Nature (2024)