Scholars@Duke
Alicia Darnell

Alicia Darnell

Assistant Professor of Pharmacology and Cancer Biology
Pharmacology & Cancer Biology
alicia.darnell@duke.edu
308 Research Drive, Durham, NC 27710

Selected Publications

A non-syndromic orofacial cleft risk locus links tRNA splicing defects to neural crest cell pathologies.

Journal Article Am J Hum Genet · May 1, 2025 Orofacial clefts are the most common form of congenital craniofacial malformation worldwide. The etiology of these birth defects is multifactorial, involving genetic and environmental factors. However, in most cases, the underlying causes remain unexplaine ... Full text Link to item Cite

Cancer tissue of origin constrains the growth and metabolism of metastases.

Journal Article Nat Metab · September 2024 Metastases arise from subsets of cancer cells that disseminate from the primary tumour1,2. The ability of cancer cells to thrive in a new tissue site is influenced by genetic and epigenetic changes that are important for disease initiation and progression, ... Full text Link to item Cite

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

Cells use multiple mechanisms for cell-cycle arrest upon withdrawal of individual amino acids.

Journal Article Cell Rep · December 26, 2023 Amino acids are required for cell growth and proliferation, but it remains unclear when and how amino acid availability impinges on the proliferation-quiescence decision. Here, we used time-lapse microscopy and single-cell tracking of cyclin-dependent kina ... Full text Link to item Cite

Nucleotide imbalance decouples cell growth from cell proliferation.

Journal Article Nat Cell Biol · August 2022 Nucleotide metabolism supports RNA synthesis and DNA replication to enable cell growth and division. Nucleotide depletion can inhibit cell growth and proliferation, but how cells sense and respond to changes in the relative levels of individual nucleotides ... Full text Link to item Cite

Methionine synthase is essential for cancer cell proliferation in physiological folate environments.

Journal Article Nat Metab · November 2021 Folate metabolism can be an effective target for cancer treatment. However, standard cell culture conditions utilize folic acid, a non-physiological folate source for most tissues. We find that the enzyme that couples folate and methionine metabolic cycles ... Full text Link to item Cite

Dissecting cell-type-specific metabolism in pancreatic ductal adenocarcinoma.

Journal Article Elife · July 10, 2020 Tumors are composed of many different cell types including cancer cells, fibroblasts, and immune cells. Dissecting functional metabolic differences between cell types within a mixed population can be challenging due to the rapid turnover of metabolites rel ... Full text Link to item Cite

Increased Serine Synthesis Provides an Advantage for Tumors Arising in Tissues Where Serine Levels Are Limiting.

Journal Article Cell Metab · June 4, 2019 Tumors exhibit altered metabolism compared to normal tissues. Many cancers upregulate expression of serine synthesis pathway enzymes, and some tumors exhibit copy-number gain of the gene encoding the first enzyme in the pathway, phosphoglycerate dehydrogen ... Full text Link to item Cite

Translational Control through Differential Ribosome Pausing during Amino Acid Limitation in Mammalian Cells.

Journal Article Mol Cell · July 19, 2018 Featured Publication Limitation for amino acids is thought to regulate translation in mammalian cells primarily by signaling through the kinases mTORC1 and GCN2. We find that a selective loss of arginine tRNA charging during limitation for arginine regulates translation throug ... Full text Link to item Cite

Pyrrolocin A, a 3-Decalinoyltetramic Acid with Selective Biological Activity, Isolated from Amazonian Cultures of the Novel Endophyte Diaporthales sp. E6927E.

Journal Article Nat Prod Commun · October 2015 Natural products remain an important source of new therapeutics for emerging drug-resistant pathogens like Candida albicans, which particularly affects immunocompromised patients. A bioactive 3-decalinoyltetramic acid, pyrrolocin A, was isolated from extra ... Link to item Cite

A viral nuclear noncoding RNA binds re-localized poly(A) binding protein and is required for late KSHV gene expression.

Journal Article PLoS Pathog · October 2011 During the lytic phase of infection, the gamma herpesvirus Kaposi's Sarcoma-Associated Herpesvirus (KSHV) expresses a highly abundant, 1.1 kb nuclear noncoding RNA of unknown function. We observe that this polyadenylated nuclear (PAN) RNA avidly binds host ... Full text Link to item Cite