Gareth Pollin

Stress granules confer an early vulnerability in KRAS-driven pancreatic tumorigenesis

Matías Estarás, Emma Cosialls, Gareth Pollin, Anass Berkachi et autres

Pancreatic ductal adenocarcinoma (PDAC) is initiated by activating KRAS mutations, yet most pancreatic cells fail to survive the induced oncogenic stress. How a subset adapts to and initiates malignant transformation remains unclear. Here, we show that stress granules (SGs) formation is a …

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PRMT5 inhibition triggers functional ATM deficiency and sensitizes pancreatic cancer to CHK1 blockade

Madeline M. Dzikowski, Gareth Pollin, Veda Gunia, Shawna M. Butler et autres

Introduction: PRMT5 inhibitors are under clinical investigation for pancreatic ductal adenocarcinoma (PDAC), but strategies to maximize their therapeutic efficacy remain undefined. Here, we sought to determine whether pharmacologic inhibition of PRMT5 creates therapeutically exploitable vulnerabilities in PDAC. Methods: We employed immunofluorescence, western …

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Mutant KRAS Heterogeneity Shapes Nuclear Architecture During Pancreatic Cancer Initiation

Gareth Pollin, Angela Mathison, Elise Leverence, Thiago M. de Assuncao et autres

BACKGROUND/OBJECTIVES: Pancreatic ductal adenocarcinoma (PDAC) arises predominantly from activating KRAS mutations, yet individual genetic variants differ markedly in signaling output and clinical impact. G12D, the most prevalent variant, strongly drives oncogenic programs, whereas G12R signals less efficiently through the AKT and ERK …

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Spatial and Transcriptional Profiling Reveals Immune Remodeling and Microenvironmental Heterogeneity in Benign and Malignant Pancreatic Neuroendocrine Tumors

Gareth Pollin, Mathison PhD Angela J., Raúl Urrutia, Gwen Lomberk et autres

An integrative multitiered computational analysis for better understanding the structure and function of 85 miniproteins

Reethika Veluri, Gareth Pollin, Jessica B. Wagenknecht, Raúl Urrutia et autres

Miniproteins, defined as polypeptides containing fewer than 50 amino acids, have recently elicited significant interest due to an emerging understanding of their diverse roles in fundamental biological processes. In addition, miniprotein dysregulation underlies human diseases and is a considerable focus for biotechnology …

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Genomic features of the methylosome protein MEP50 and its implications in hormone signaling and cancer

Gareth Pollin, Young‐In Chi, Raúl Urrutia, Gwen Lomberk

Abstract: Dysfunction of several WD40 family proteins causes diverse endocrine diseases. Until recently, MEP50, a WD40 protein, was considered a gene of unknown significance because no inherited disease had been linked to its function. However, genetic inactivation of MEP50 in mouse models …

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Abstract 2504 Phosphorylation of PRMT5-MEP50 Methylosome Regulates Cytoplasmic Stress Granule Formation in Pancreatic Cancer

Gareth Pollin, Young‐In Chi, Juan Iovanna, Angela Mathison et autres

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Abstract 2539 Defining the Molecular Heterogeneity and Functional Impact of Pancreatic Cancer-Associated KRAS Mutations

Gareth Pollin, Angela Mathison, Young‐In Chi, Juan Iovanna et autres

KRAS mutations are the initiating factor in approximately 93% of pancreatic adenocarcinoma (PDAC). Consequently, we investigated the molecular landscapes shaped by the six most common PDAC-associated KRAS mutations (G12D, G12R, G12V, Q61H, Q61K, Q61R) to better understand PDAC-initiating signaling. We engineered human …

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Abstract 2418 Dual Inhibition of PRMT5 and CHK1 Drives Cell Cycle Arrest, Transcriptional Reprogramming, and Apoptosis in Pancreatic Ductal Adenocarcinoma

Madeline M. Dzikowski, Veda Gunia, Guillermo Urrutia, Caitlyn Clouse et autres

Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer-related deaths in the United States, with a dismal 5-year survival rate of only 13%. Despite advances in cancer therapies, survival outcomes for PDAC patients have seen only marginal improvements, highlighting an …

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An Integrative Multitiered Computational Analysis for Better Understanding the Structure and Function of 85 Miniproteins

Reethika Veluri, Gareth Pollin, Jessica B. Wagenknecht, Raúl Urrutia et autres

Background: Miniproteins, defined as polypeptides containing fewer than 50 amino acids, have recently elicited significant interest due to an emerging understanding of their diverse roles in fundamental biological processes. In addition, miniprotein dysregulation underlies human diseases and is a significant focus for …

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Emergent properties of the lysine methylome reveal regulatory roles via protein interactions and histone mimicry

Gareth Pollin, Young‐In Chi, Angela Mathison, Michael T. Zimmermann et autres

AIMS: Epigenomics has significantly advanced through the incorporation of Systems Biology approaches. This study aims to investigate the human lysine methylome as a system, using a data-science approach to reveal its emergent properties, particularly focusing on histone mimicry and the broader implications …

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Mutant KRAS inhibitors enter the scene of precision therapeutics for pancreatic cancer

Gareth Pollin, Gwen Lomberk, Angela Mathison, Michael T. Zimmermann et autres

age-standardized rate (ASR) incidence of 4.

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