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Christopher Chidley

Assistant Professor of Pharmacology and Cancer Biology
Pharmacology & Cancer Biology
308 Research Drive, Durham, NC 27710

Selected Publications


Nucleotide depletion promotes cell fate transitions by inducing DNA replication stress.

Journal Article Dev Cell · August 19, 2024 Control of cellular identity requires coordination of developmental programs with environmental factors such as nutrient availability, suggesting that perturbing metabolism can alter cell state. Here, we find that nucleotide depletion and DNA replication s ... Full text Link to item Cite

A CRISPRi/a screening platform to study cellular nutrient transport in diverse microenvironments.

Journal Article Nat Cell Biol · May 2024 Blocking the import of nutrients essential for cancer cell proliferation represents a therapeutic opportunity, but it is unclear which transporters to target. Here we report a CRISPR interference/activation screening platform to systematically interrogate ... Full text Open Access Link to item Cite

An enhanced isothermal amplification assay for viral detection.

Journal Article Nat Commun · November 20, 2020 Rapid, inexpensive, robust diagnostics are essential to control the spread of infectious diseases. Current state of the art diagnostics are highly sensitive and specific, but slow, and require expensive equipment. Here we report the development of a molecu ... Full text Open Access Link to item Cite

Receptor-Driven ERK Pulses Reconfigure MAPK Signaling and Enable Persistence of Drug-Adapted BRAF-Mutant Melanoma Cells.

Journal Article Cell Syst · November 18, 2020 Targeted inhibition of oncogenic pathways can be highly effective in halting the rapid growth of tumors but often leads to the emergence of slowly dividing persister cells, which constitute a reservoir for the selection of drug-resistant clones. In BRAFV60 ... Full text Link to item Cite

A curative combination cancer therapy achieves high fractional cell killing through low cross-resistance and drug additivity.

Journal Article Elife · November 19, 2019 Curative cancer therapies are uncommon and nearly always involve multi-drug combinations developed by experimentation in humans; unfortunately, the mechanistic basis for the success of such combinations has rarely been investigated in detail, obscuring les ... Full text Open Access Link to item Cite

The anticancer natural product ophiobolin A induces cytotoxicity by covalent modification of phosphatidylethanolamine.

Journal Article Elife · July 12, 2016 Phenotypic screens allow the identification of small molecules with promising anticancer activity, but the difficulty in characterizing the mechanism of action of these compounds in human cells often undermines their value as drug leads. Here, we used a lo ... Full text Link to item Cite

A yeast-based screen reveals that sulfasalazine inhibits tetrahydrobiopterin biosynthesis.

Journal Article Nat Chem Biol · June 2011 We introduce an approach for detection of drug-protein interactions that combines a new yeast three-hybrid screening for identification of interactions with affinity chromatography for their unambiguous validation. We applied the methodology to the profili ... Full text Link to item Cite

Searching for the protein targets of bioactive molecules.

Journal Article Chimia (Aarau) · 2011 The identification of all protein targets of a given drug or bioactive molecule within the human body is a prerequisite for an understanding of its beneficial and deleterious activities. Current approaches to reveal protein targets often fail to reveal phy ... Full text Link to item Cite

A designed protein for the specific and covalent heteroconjugation of biomolecules.

Journal Article Bioconjug Chem · September 2008 Bioconjugations often rely on adaptor molecules to cross-link different biomolecules. In this work, we introduce the molecular adaptor covalin, which is a protein chimera of two self-labeling proteins with nonoverlapping substrate specificity. Covalin perm ... Full text Link to item Cite

Directed evolution of O6-alkylguanine-DNA alkyltransferase for applications in protein labeling.

Journal Article Protein Eng Des Sel · July 2006 The specific reaction of O6-alkylguanine-DNA alkyltransferase (AGT) with O6-benzylguanine (BG) derivatives allows for a specific labeling of AGT fusion proteins with chemically diverse compounds in living cells and in vitro. The efficiency of the labeling ... Full text Link to item Cite