Michael Costanzo

Yra2 regulates proteolysis of Cse4 to prevent its mislocalization to non-centromeric regions for chromosomal stability in budding yeast

This paper identifies Yra2's role in ubiquitin-mediated proteolysis of Cse4 to prevent its mislocalization and maintain chromosomal stability in budding yeast.

The Nematicide Tioxazafen Disrupts Proteasome Function via Cytochrome P450 Bioactivation

This study shows tioxazafen is bioactivated by cytochrome P450s into a proteasome disruptor, leading to toxicity in nematodes and potential human skin reactions.

Expanding TheCellMap.org to visualize a genome-scale genetic interaction network for a human cell line

The paper expands TheCellMap.org to include human genetic interactions from CRISPR-based analysis in HAP1 cells, enabling visualization and exploration of the network.

Quantitative analysis of genetic interactions in human cells from genome-wide CRISPR-Cas9 screens

The paper develops a method to quantify genetic interactions from CRISPR-Cas9 screens and identifies systematic variations in screen data.

A global genetic interaction map of a human cell reveals conserved principles of genetic networks

The paper constructs a genome-scale genetic interaction network from 4 million double mutants in HAP1 cells, revealing conserved genetic network principles across species and uncovering novel gene functions and cancer dependencies.

A scalable platform for efficient CRISPR-Cas9 chemical-genetic screens of DNA damage-inducing compounds

The paper presents a scalable CRISPR-Cas9 platform for chemical-genetic screens of DNA damage-inducing compounds, identifying enriched modes-of-action and revealing late ICL repair pathway responses.

N-terminal acetylation shields proteins from degradation and promotes age-dependent motility and longevity

The paper shows that N-terminal acetylation by NatC protects proteins from degradation, enhancing longevity and motility, and that UBR4-KCMF1 targets unacetylated N-terminal Met followed by hydrophobic residues.

Reproducibility metrics for CRISPR screens

The paper identifies limitations in current reproducibility metrics for CRISPR screens and advocates for context-sensitive metrics to better assess screen quality.

Major functional bias for mitochondrial complexes in genome-wide CRISPR screens

The paper introduces FLEX, a pipeline for benchmarking CRISPR screen data, and identifies a dominant mitochondria-associated signal in genome-wide screens.

Systematic mapping of genetic interactions for de novo fatty acid synthesis

This study maps genetic interactions in FASN-deficient cells to identify genes involved in lipid uptake and metabolic adaptation.

Reduced Gene Dosage of Histone H4 Prevents CENP-A Mislocalization in Saccharomyces cerevisiae

This study identifies genes that contribute to mislocalization of overexpressed Cse4 and shows reduced H4 dosage facilitates Cse4 sumoylation and mislocalization, leading to synthetic dosage lethality.

Discovering genetic interactions bridging pathways in genome-wide association studies

This paper introduces BridGE, a method to detect pathway-level genetic interactions from GWAS data, revealing significant interactions in multiple diseases.

Predicting bioprocess targets of chemical compounds through integration of chemical-genetic and genetic interaction networks

The paper develops CG-TARGET to predict compound biological processes by integrating chemical-genetic and genetic interaction networks, showing improved accuracy and FDR control.

Functional Annotation of Chemical Libraries across Diverse Biological Processes

This study develops a yeast-based chemical-genetic screening system to annotate compound functionality across biological processes and identifies compounds with dual modes of action.

Efficient strategies for screening large-scale genetic interaction networks

The paper introduces COMPRESS-GI, an algorithm that efficiently selects informative genes for genetic interaction screens, enabling large-scale chemical genetic screens with high throughput.

Systematic identification of pleiotropic genes from genetic interactions

The paper measures pleiotropy in yeast genes using genetic interaction networks, finding high-pleiotropy genes have broader functional influence and distinct characteristics compared to low-pleiotropy genes.