About

Ashley Shay is an Affiliate Professor in the Department of Veterinary and Biomedical Sciences at Pennsylvania State University. She serves as the Director of the Metabolomics Core Facility at the Huck Institutes of Life Sciences. Her professional contact information includes her email aes5254@psu.edu and office phone number 814-863-2274. She uses the pronouns She/Her. Further details about her research focus, background, or key contributions are not provided in the available page text.

Research topics

• Immunology
• Chemistry
• Virology
• Medicine
• Cell biology
• Biochemistry
• Biology
• Pathology
• Internal medicine

Selected publications

• Sequestration of plant defenses by spotted lanternfly (Lycorma delicatula) and effects on avian predators

  Journal of Chemical Ecology · 2025-10-23

  articleOpen access

  Lycorma delicatula is a polyphagous phloem feeder, which is spreading rapidly in the U.S., and is a major threat to grapes, hops, and ornamentals. Among its hosts, L. delicatula prefers Ailanthus altissima, an invasive tree from which it sequesters toxins, including several quassinoid compounds. We tested how these defenses affected predation by birds of nymphal and adult L. delicatula. Freeze-killed nymphs of each instar were reared with or without access to A. altissima and placed into cups on top of nest boxes occupied by house wrens (Troglodytes aedon). House wrens ate or fed their chicks a greater proportion of L. delicatula nymphs that had not had access to A. altissima than the nymphs that had access to this host plant. Adult L. delicatula reared with or without access to A. altissima were ground up and incorporated into separate batches of suet that were placed into double sided feeders set up at different sites during the winter. Trail camera video was reviewed to record how many times birds pecked each suet cake. Birds pecked the suet containing L. delicatula reared without access to A. altissima significantly more frequently than the suet containing adults that had fed on A. altissima. Of the quassinoids sequestered by L. delicatula from phloem sap of A. altissima, ailanthone and four other quassinoids were identified and quantified in different tissues, with the highest concentrations in the salivary glands. Results suggest that sequestration of toxic chemicals from A. altissima provides some protection to L. delicatula from avian predators.

  PublisherOA PDFDOI

• Adaptation to cystine limitation stress confers a targetable lipid metabolism vulnerability in pancreatic ductal adenocarcinoma

  Nature Communications · 2025-12-31

  articleOpen access

  Cystine/cysteine is critical for antioxidant response and sulfur metabolism in cancer cells and is one of the most depleted amino acids in the microenvironment of pancreatic ductal adenocarcinoma (PDAC). The effects of cystine limitation stress (CLS) on PDAC progression are poorly understood. Here we report that adaptation to CLS (CLSA) promotes PDAC cell proliferation and tumor growth through translational upregulation of the oxidative pentose phosphate pathway (OxPPP). OxPPP activates the de novo synthesis of nucleotides and fatty acids to support tumor growth. On the other hand, CLSA-mediated lipidomic reprogramming depends on triacylglycerides synthesis and lipid droplet formation to mitigate lipotoxicity. Through drug screening, we identify lomitapide as an inhibitor of CLSA PDAC tumor growth and a potent sensitizer of chemotherapy. Lomitapide inhibits triacylglycerides synthesis to interfere with CLSA and chemotherapy-induced lipidomic reprogramming. Taken together, we demonstrate that CLSA promotes PDAC tumor growth through metabolic reprogramming and lomitapide could be used to target the dysregulated lipid metabolism in PDAC.

  PublisherDOI

• Library Enabling Annotation of Botanical Natural Products (LEAFBot): An Open-Access Library of Mass Spectrometry Fragmentation Spectra for Plant Metabolites

  Journal of the American Society for Mass Spectrometry · 2025-04-18 · 1 citations

  article

  Many existing mass spectral libraries focus on human or microbially derived molecules. Few plant-specific MS2 databases exist, making annotation of botanical samples difficult. To fill this gap in mass spectrometry data availability, the Library Enabling Annotation of Botanical Natural Products (LEAFBot) was constructed. Using a flow injection mass spectrometry method that allowed for rapid throughput data collection, the MS2 spectra of >300 pure botanical secondary metabolites were experimentally measured and complied into a single library housed in the Global Natural Products Social Molecular Networking (GNPS) spectral database. Of these compounds, over 20% were not present in the existing GNPS database, and 11% were not present in any of three main mass spectral databases (GNPS, Metlin, and MassBank). Additionally, LEAFBot contains a wider range of adducts compared to other plant-based mass spectral libraries, enabling more effective annotation of unknown features. The LEAFBot database represents a new resource to the mass spectrometry and metabolomics community seeking to characterize plant-based samples. The possibility of searching against a taxonomically specific library decreases the likelihood of false positives in database searches, and the ease of adding new spectra, following procedures outlined herein, will enable community-lead expansion of the database.

  PublisherDOI

• ADVANCEMENTS IN CLOSED AND AUTOMATED CD34+ HEMATOPOIETIC STEM AND PROGENITOR CELL MANUFACTURING UTILIZING THE MILTENYI CLINIMACS PRODIGY SYSTEM: ENABLING COST-EFFECTIVE NEXT-GENERATION THERAPIES

  Cytotherapy · 2024-05-22 · 1 citations

  article
  PublisherDOI

• Upregulated selenoprotein I during lipopolysaccharide-induced B cell activation promotes lipidomic changes and is required for effective differentiation into IgM-secreting plasma B cells

  Journal of Leukocyte Biology · 2024-01-29 · 6 citations

  articleOpen access

  The mechanisms driving metabolic reprogramming during B cell activation are unclear, particularly roles for enzymatic pathways involved in lipid remodeling. We found that murine B cell activation with lipopolysaccharide (LPS) led to a 1.6-fold increase in total lipids that included higher levels of phosphatidylethanolamine (PE) and plasmenyl PE. Selenoprotein I (SELENOI) is an ethanolamine phospholipid transferase involved in the synthesis of both PE and plasmenyl PE, and SELENOI expression was also upregulated during activation. Selenoi knockout (KO) B cells exhibited decreased levels of plasmenyl PE, which plays an important antioxidant role. Lipid peroxidation was measured and found to increase ∼2-fold in KO vs. wild-type (WT) B cells. Cell death was not impacted by KO in LPS-treated B cells and proliferation was only slightly reduced, but differentiation into CD138 + Blimp-1+ plasma B cells was decreased ∼2-fold. This led to examination of B cell receptors important for differentiation that recognize the ligand B cell activating factor, and levels of TACI (transmembrane activator, calcium-modulator, and cytophilin ligand interactor) (CD267) were significantly decreased on KO B cells compared with WT control cells. Vaccination with ovalbumin/adjuvant led to decreased ovalbumin-specific immunoglobulin M (IgM) levels in sera of KO mice compared with WT mice. Real-time polymerase chain reaction analyses revealed a decreased switch from surface to secreted IgM in spleens of KO mice induced by vaccination or LP-BM5 retrovirus infection. Overall, these findings detail the lipidomic response of B cells to LPS activation and reveal the importance of upregulated SELENOI for promoting differentiation into IgM-secreting plasma B cells.

  PublisherOA PDFDOI

• Adaptation to cystine limitation stress confers a targetable lipid metabolism vulnerability in pancreatic ductal adenocarcinoma

  bioRxiv (Cold Spring Harbor Laboratory) · 2024-12-17 · 1 citations

  preprintOpen access

  Abstract Cystine/cysteine is critical for antioxidant response and sulfur metabolism in cancer cells and is one of the most depleted amino acids in the microenvironment of pancreatic ductal adenocarcinoma (PDAC). The effects of cystine limitation stress (CLS) on PDAC progression are poorly understood. Here we report that adaptation to CLS (CLSA) promotes PDAC cell proliferation and tumor growth through translational upregulation of the oxidative pentose phosphate pathway (OxPPP). OxPPP activates the de novo synthesis of nucleotides and fatty acids to support tumor growth. On the other hand, CLSA-mediated lipidomic reprogramming depends on triacylglycerides synthesis and lipid droplet formation to mitigate lipotoxicity. Through drug screening, we identify lomitapide as an inhibitor of CLSA PDAC tumor growth and a potent sensitizer of chemotherapy. Lomitapide inhibits triacylglycerides synthesis to interfere with CLSA and chemotherapy-induced lipidomic reprogramming. Taken together, we demonstrate that CLSA promotes PDAC tumor growth through metabolic reprogramming and lomitapide could be used to target the dysregulated lipid metabolism in PDAC.

  PublisherOA PDFDOI

• SCALING MANUFACTURING OF CD34+ HEMATOPOIETIC STEM AND PROGENITOR CELLS (HSPCs) WITH AN AUTOMATED AND INTEGRATED CELL ISOLATION SYSTEM

  Cytotherapy · 2024-05-22 · 1 citations

  article
  PublisherDOI

• Selenoprotein I is indispensable for ether lipid homeostasis and proper myelination

  Journal of Biological Chemistry · 2024-04-05 · 8 citations

  articleOpen access

  Selenoprotein I (SELENOI) catalyzes the final reaction of the CDP-ethanolamine branch of the Kennedy pathway, generating the phospholipids phosphatidylethanolamine (PE) and plasmenyl-PE. Plasmenyl-PE is a key component of myelin and is characterized by a vinyl ether bond that preferentially reacts with oxidants, thus serves as a sacrificial antioxidant. In humans, multiple loss-of-function mutations in genes affecting plasmenyl-PE metabolism have been implicated in hereditary spastic paraplegia, including SELENOI. Herein, we developed a mouse model of nervous system-restricted SELENOI deficiency that circumvents embryonic lethality caused by constitutive deletion and recapitulates phenotypic features of hereditary spastic paraplegia. Resulting mice exhibited pronounced alterations in brain lipid composition, which coincided with motor deficits and neuropathology including hypomyelination, elevated reactive gliosis, and microcephaly. Further studies revealed increased lipid peroxidation in oligodendrocyte lineage cells and disrupted oligodendrocyte maturation both in vivo and in vitro. Altogether, these findings detail a critical role for SELENOI-derived plasmenyl-PE in myelination that is of paramount importance for neurodevelopment.

  PublisherOA PDFDOI

• P10-013-23 Differences in Metabolomic Profiles Between Responders and Non-responders of Prune Supplementation on Bone Health in Postmenopausal Women

  Current Developments in Nutrition · 2023-07-01

  articleOpen access
  PublisherDOI

• Eosinophil Phenotypes Are Functionally Regulated by Resolvin D2 during Allergic Lung Inflammation

  American Journal of Respiratory Cell and Molecular Biology · 2023-08-08 · 15 citations

  articleOpen access

  Abstract Eosinophils (Eos) reside in multiple organs during homeostasis and respond rapidly to an inflammatory challenge. Although Eos share chemical staining properties, they also demonstrate phenotypic and functional plasticity that is not fully understood. Here, we used a murine model of allergic lung inflammation to characterize Eos subsets and determine their spatiotemporal and functional regulation during inflammation and its resolution in response to resolvin D2 (RvD2), a potent specialized proresolving mediator. Two Eos subsets were identified by CD101 expression with distinct anatomic localization and transcriptional signatures at baseline and during inflammation. CD101low Eos were predominantly located in a lung vascular niche and responded to allergen challenge by moving into the lung interstitium. CD101high Eos were predominantly located in bronchoalveolar lavage (BAL) and extravascular lung, only present during inflammation, and had transcriptional evidence for cell activation. RvD2 reduced total Eos numbers and changed their phenotype and activation by at least two distinct mechanisms: decreasing interleukin 5-dependent recruitment of CD101low Eos and decreasing conversion of CD101low Eos to CD101high Eos. Collectively, these findings indicate that Eos are a heterogeneous pool of cells with distinct activation states and spatiotemporal regulation during resolution of inflammation and that RvD2 is a potent proresolving mediator for Eos recruitment and activation.

  PublisherOA PDFDOI

Frequent coauthors

• Charles N. Serhan

  Brigham and Women's Hospital

  41 shared

• Robert Nshimiyimana

  Harvard University Press

  18 shared

• Bradley A. Carlson

  National Cancer Institute

  13 shared

• K. Sandeep Prabhu

  Max Planck Institute for Biology of Ageing

  13 shared

• Bruce D. Levy

  Brigham and Women's Hospital

  9 shared

• Rachel L. Markley

  Cleveland Clinic

  9 shared

• Thayse R. Brüggemann

  Harvard University

  9 shared

• Kalyan K. Dewan

  University of Georgia

  7 shared

Education

• Ph.D., Animal Science

  University of California, Davis

  2005

• M.S., Animal Science

  University of California, Davis

  2000

• B.S., Animal Science

  University of California, Davis

  1998