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William Richard Jeck

Assistant Professor of Pathology
Pathology
40 Duke Medicine Circle, 3017 Yellow Zone, Durham, NC 27710

Selected Publications


Acoustic separation and concentration of exosomes for nucleotide detection: ASCENDx.

Journal Article Sci Adv · March 8, 2024 Efficient isolation and analysis of exosomal biomarkers hold transformative potential in biomedical applications. However, current methods are prone to contamination and require costly consumables, expensive equipment, and skilled personnel. Here, we intro ... Full text Link to item Cite

Successful AAV8 readministration: Suppression of capsid-specific neutralizing antibodies by a combination treatment of bortezomib and CD20 mAb in a mouse model of Pompe disease.

Journal Article J Gene Med · August 2023 BACKGROUND: A major challenge to adeno-associated virus (AAV)-mediated gene therapy is the presence of anti-AAV capsid neutralizing antibodies (NAbs), which can block viral vector transduction even at very low titers. In the present study, we examined the ... Full text Open Access Link to item Cite

Anal Carcinoma, Version 2.2023, NCCN Clinical Practice Guidelines in Oncology.

Journal Article J Natl Compr Canc Netw · June 2023 This discussion summarizes the NCCN Clinical Practice Guidelines for managing squamous cell anal carcinoma, which represents the most common histologic form of the disease. A multidisciplinary approach including physicians from gastroenterology, medical on ... Full text Link to item Cite

A League of Its Own? Established and Emerging Therapies in Undifferentiated Pleomorphic Sarcoma.

Journal Article Curr Treat Options Oncol · March 2023 Over the last decade in soft tissue sarcoma (STS) research, the shifting landscape towards more precise subtype classification and the increasing study of novel therapeutic strategies has prompted a need to highlight current knowledge of effective subtype ... Full text Link to item Cite

miRNA probe integrated biosensor platform using bimetallic nanostars for amplification-free multiplexed detection of circulating colorectal cancer biomarkers in clinical samples.

Journal Article Biosens Bioelectron · January 15, 2023 There is a critical need for sensitive and rapid detection technologies utilizing molecular biotargets such as microRNAs (miRNAs), which regulate gene expression and are a promising class of diagnostic biomarkers for disease detection. Here, we present the ... Full text Link to item Cite

Circulating Tumor DNA Testing Overcomes Limitations of Comprehensive Genomic Profiling from Tumor Tissue.

Journal Article Case Rep Oncol · 2023 "Liquid biopsy" is an established technique for examining circulating tumor DNA (ctDNA) from a routine blood draw and detecting actionable biomarkers. Nonetheless, ctDNA testing is rarely utilized for patients with newly diagnosed metastatic colorectal can ... Full text Link to item Cite

A Rare Cause of Confluent Abnormal Esophageal Mucosa.

Journal Article Gastroenterology · October 2022 Full text Link to item Cite

Rectal Cancer, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology.

Journal Article J Natl Compr Canc Netw · October 2022 This selection from the NCCN Guidelines for Rectal Cancer focuses on management of malignant polyps and resectable nonmetastatic rectal cancer because important updates have been made to these guidelines. These recent updates include redrawing the algorith ... Full text Link to item Cite

Self-activating G protein α subunits engage seven-transmembrane regulator of G protein signaling (RGS) proteins and a Rho guanine nucleotide exchange factor effector in the amoeba Naegleria fowleri.

Journal Article J Biol Chem · August 2022 The free-living amoeba Naegleria fowleri is a causative agent of primary amoebic meningoencephalitis and is highly resistant to current therapies, resulting in mortality rates >97%. As many therapeutics target G protein-centered signal transduction pathway ... Full text Link to item Cite

Delivery of therapeutic carbon monoxide by gas-entrapping materials.

Journal Article Sci Transl Med · June 29, 2022 Carbon monoxide (CO) has long been considered a toxic gas but is now a recognized bioactive gasotransmitter with potent immunomodulatory effects. Although inhaled CO is currently under investigation for use in patients with lung disease, this mode of admin ... Full text Link to item Cite

The Role of Machine Learning in Cardiovascular Pathology.

Journal Article Can J Cardiol · February 2022 Machine learning has seen slow but steady uptake in diagnostic pathology over the past decade to assess digital whole-slide images. Machine learning tools have incredible potential to standardise, and likely even improve, histopathologic diagnoses, but the ... Full text Link to item Cite

BET Protein Inhibition Regulates Macrophage Chromatin Accessibility and Microbiota-Dependent Colitis.

Journal Article Front Immunol · 2022 INTRODUCTION: In colitis, macrophage functionality is altered compared to normal homeostatic conditions. Loss of IL-10 signaling results in an inappropriate chronic inflammatory response to bacterial stimulation. It remains unknown if inhibition of bromodo ... Full text Link to item Cite

A Case of Microsatellite Instability-High Colon Cancer in a Young Woman With Familial Adenomatous Polyposis.

Journal Article J Natl Compr Canc Netw · December 2021 Two major molecular pathways of colorectal carcinogenesis, chromosomal instability (CIN) and microsatellite instability (MSI), are considered to be mutually exclusive. Distinguishing CIN from MSI-high tumors has considerable therapeutic implications, becau ... Full text Link to item Cite

Primary hepatic neoplasms arising in cirrhotic livers can have a variable spectrum of neuroendocrine differentiation.

Journal Article Hum Pathol · October 2021 Primary hepatic neoplasms with neuroendocrine differentiation are extremely rare. Their clinicopathological features and molecular genetic basis are largely unknown. We identified four cases of primary hepatic neoplasms with neuroendocrine differentiation. ... Full text Link to item Cite

Personalized Radiation Attenuating Materials for Gastrointestinal Mucosal Protection.

Journal Article Adv Sci (Weinh) · June 2021 Cancer patients undergoing therapeutic radiation routinely develop injury of the adjacent gastrointestinal (GI) tract mucosa due to treatment. To reduce radiation dose to critical GI structures including the rectum and oral mucosa, 3D-printed GI radioprote ... Full text Link to item Cite

Nanopore Flongle Sequencing as a Rapid, Single-Specimen Clinical Test for Fusion Detection.

Journal Article J Mol Diagn · May 2021 The identification of gene fusions is a cornerstone of diagnosis and treatment decision making for tumors of many forms and primary sites. Diverse molecular approaches are currently used for the molecular diagnosis of fusions, but few permit broad, partner ... Full text Link to item Cite

LGR5 in Barrett's Esophagus and its Utility in Predicting Patients at Increased Risk of Advanced Neoplasia.

Journal Article Clin Transl Gastroenterol · December 22, 2020 INTRODUCTION: The expression of LGR5, a known stem cell marker, is poorly understood in Barrett's esophagus (BE) and related neoplasia. The aim of this study was to evaluate LGR5 in BE and related neoplasia and to evaluate its utility as a potential biomar ... Full text Link to item Cite

Lymph node metastases develop through a wider evolutionary bottleneck than distant metastases.

Journal Article Nat Genet · July 2020 Genetic diversity among metastases is poorly understood but contains important information about disease evolution at secondary sites. Here we investigate inter- and intra-lesion heterogeneity for two types of metastases that associate with different clini ... Full text Link to item Cite

Acoustic separation and concentration of exosomes for nucleotide detection: ASCENDx.

Journal Article Sci Adv · March 8, 2024 Efficient isolation and analysis of exosomal biomarkers hold transformative potential in biomedical applications. However, current methods are prone to contamination and require costly consumables, expensive equipment, and skilled personnel. Here, we intro ... Full text Link to item Cite

Successful AAV8 readministration: Suppression of capsid-specific neutralizing antibodies by a combination treatment of bortezomib and CD20 mAb in a mouse model of Pompe disease.

Journal Article J Gene Med · August 2023 BACKGROUND: A major challenge to adeno-associated virus (AAV)-mediated gene therapy is the presence of anti-AAV capsid neutralizing antibodies (NAbs), which can block viral vector transduction even at very low titers. In the present study, we examined the ... Full text Open Access Link to item Cite

Anal Carcinoma, Version 2.2023, NCCN Clinical Practice Guidelines in Oncology.

Journal Article J Natl Compr Canc Netw · June 2023 This discussion summarizes the NCCN Clinical Practice Guidelines for managing squamous cell anal carcinoma, which represents the most common histologic form of the disease. A multidisciplinary approach including physicians from gastroenterology, medical on ... Full text Link to item Cite

A League of Its Own? Established and Emerging Therapies in Undifferentiated Pleomorphic Sarcoma.

Journal Article Curr Treat Options Oncol · March 2023 Over the last decade in soft tissue sarcoma (STS) research, the shifting landscape towards more precise subtype classification and the increasing study of novel therapeutic strategies has prompted a need to highlight current knowledge of effective subtype ... Full text Link to item Cite

miRNA probe integrated biosensor platform using bimetallic nanostars for amplification-free multiplexed detection of circulating colorectal cancer biomarkers in clinical samples.

Journal Article Biosens Bioelectron · January 15, 2023 There is a critical need for sensitive and rapid detection technologies utilizing molecular biotargets such as microRNAs (miRNAs), which regulate gene expression and are a promising class of diagnostic biomarkers for disease detection. Here, we present the ... Full text Link to item Cite

Circulating Tumor DNA Testing Overcomes Limitations of Comprehensive Genomic Profiling from Tumor Tissue.

Journal Article Case Rep Oncol · 2023 "Liquid biopsy" is an established technique for examining circulating tumor DNA (ctDNA) from a routine blood draw and detecting actionable biomarkers. Nonetheless, ctDNA testing is rarely utilized for patients with newly diagnosed metastatic colorectal can ... Full text Link to item Cite

A Rare Cause of Confluent Abnormal Esophageal Mucosa.

Journal Article Gastroenterology · October 2022 Full text Link to item Cite

Rectal Cancer, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology.

Journal Article J Natl Compr Canc Netw · October 2022 This selection from the NCCN Guidelines for Rectal Cancer focuses on management of malignant polyps and resectable nonmetastatic rectal cancer because important updates have been made to these guidelines. These recent updates include redrawing the algorith ... Full text Link to item Cite

Self-activating G protein α subunits engage seven-transmembrane regulator of G protein signaling (RGS) proteins and a Rho guanine nucleotide exchange factor effector in the amoeba Naegleria fowleri.

Journal Article J Biol Chem · August 2022 The free-living amoeba Naegleria fowleri is a causative agent of primary amoebic meningoencephalitis and is highly resistant to current therapies, resulting in mortality rates >97%. As many therapeutics target G protein-centered signal transduction pathway ... Full text Link to item Cite

Delivery of therapeutic carbon monoxide by gas-entrapping materials.

Journal Article Sci Transl Med · June 29, 2022 Carbon monoxide (CO) has long been considered a toxic gas but is now a recognized bioactive gasotransmitter with potent immunomodulatory effects. Although inhaled CO is currently under investigation for use in patients with lung disease, this mode of admin ... Full text Link to item Cite

The Role of Machine Learning in Cardiovascular Pathology.

Journal Article Can J Cardiol · February 2022 Machine learning has seen slow but steady uptake in diagnostic pathology over the past decade to assess digital whole-slide images. Machine learning tools have incredible potential to standardise, and likely even improve, histopathologic diagnoses, but the ... Full text Link to item Cite

BET Protein Inhibition Regulates Macrophage Chromatin Accessibility and Microbiota-Dependent Colitis.

Journal Article Front Immunol · 2022 INTRODUCTION: In colitis, macrophage functionality is altered compared to normal homeostatic conditions. Loss of IL-10 signaling results in an inappropriate chronic inflammatory response to bacterial stimulation. It remains unknown if inhibition of bromodo ... Full text Link to item Cite

A Case of Microsatellite Instability-High Colon Cancer in a Young Woman With Familial Adenomatous Polyposis.

Journal Article J Natl Compr Canc Netw · December 2021 Two major molecular pathways of colorectal carcinogenesis, chromosomal instability (CIN) and microsatellite instability (MSI), are considered to be mutually exclusive. Distinguishing CIN from MSI-high tumors has considerable therapeutic implications, becau ... Full text Link to item Cite

Primary hepatic neoplasms arising in cirrhotic livers can have a variable spectrum of neuroendocrine differentiation.

Journal Article Hum Pathol · October 2021 Primary hepatic neoplasms with neuroendocrine differentiation are extremely rare. Their clinicopathological features and molecular genetic basis are largely unknown. We identified four cases of primary hepatic neoplasms with neuroendocrine differentiation. ... Full text Link to item Cite

Personalized Radiation Attenuating Materials for Gastrointestinal Mucosal Protection.

Journal Article Adv Sci (Weinh) · June 2021 Cancer patients undergoing therapeutic radiation routinely develop injury of the adjacent gastrointestinal (GI) tract mucosa due to treatment. To reduce radiation dose to critical GI structures including the rectum and oral mucosa, 3D-printed GI radioprote ... Full text Link to item Cite

Nanopore Flongle Sequencing as a Rapid, Single-Specimen Clinical Test for Fusion Detection.

Journal Article J Mol Diagn · May 2021 The identification of gene fusions is a cornerstone of diagnosis and treatment decision making for tumors of many forms and primary sites. Diverse molecular approaches are currently used for the molecular diagnosis of fusions, but few permit broad, partner ... Full text Link to item Cite

LGR5 in Barrett's Esophagus and its Utility in Predicting Patients at Increased Risk of Advanced Neoplasia.

Journal Article Clin Transl Gastroenterol · December 22, 2020 INTRODUCTION: The expression of LGR5, a known stem cell marker, is poorly understood in Barrett's esophagus (BE) and related neoplasia. The aim of this study was to evaluate LGR5 in BE and related neoplasia and to evaluate its utility as a potential biomar ... Full text Link to item Cite

Lymph node metastases develop through a wider evolutionary bottleneck than distant metastases.

Journal Article Nat Genet · July 2020 Genetic diversity among metastases is poorly understood but contains important information about disease evolution at secondary sites. Here we investigate inter- and intra-lesion heterogeneity for two types of metastases that associate with different clini ... Full text Link to item Cite

Texture Analysis of Magnetic Resonance Enterography Contrast Enhancement Can Detect Fibrosis in Crohn Disease Strictures.

Journal Article J Pediatr Gastroenterol Nutr · November 2019 OBJECTIVE: The aim of the study was to investigate if texture analysis of contrast-enhanced magnetic resonance enterography (MRE) images can determine Crohn disease (CD) stricture histologic type. MATERIALS AND METHODS: A radiology report database query id ... Full text Link to item Cite

The Difference Between Unfixed and Postfixation Placental Weight.

Journal Article Am J Clin Pathol · July 5, 2019 OBJECTIVES: Reference values for placental weights correlated with gestational age are used in surgical pathology. Most reference values were established for fresh placentas. Some laboratories routinely fix all placentas, bringing into question the accurac ... Full text Link to item Cite

A Nanopore Sequencing-Based Assay for Rapid Detection of Gene Fusions.

Journal Article J Mol Diagn · January 2019 Structural chromosomal rearrangements leading to gene fusions are strong driver mutations in a variety of tumors. Identification of specific gene fusions can be essential for distinguishing benign from malignant conditions and for recognizing specific subt ... Full text Link to item Cite

A Conserved Distal Lung Regenerative Pathway in Acute Lung Injury.

Journal Article Am J Pathol · May 2018 Improved tools have led to a burgeoning understanding of lung regeneration in mice, but it is not yet known how these insights may be relevant to acute lung injury in humans. We report in detail two cases of fulminant idiopathic acute lung injury requiring ... Full text Link to item Cite

Lung Cancers Associated With Cystic Airspaces: Natural History, Pathologic Correlation, and Mutational Analysis.

Journal Article J Thorac Imaging · May 2017 PURPOSE: The aim of the study was to investigate the natural history of non-small cell lung cancers (NSCLCs) associated with cystic airspaces, including histopathology and molecular analysis. MATERIALS AND METHODS: A total of 34,801 computed tomographic (C ... Full text Link to item Cite

Harnessing TCGA RNAseq Data as a Springboard to Novel Tumor Markers

Conference LABORATORY INVESTIGATION · February 1, 2017 Link to item Cite

Subtyping sub-Saharan esophageal squamous cell carcinoma by comprehensive molecular analysis.

Journal Article JCI Insight · October 6, 2016 Esophageal squamous cell carcinoma (ESCC) is endemic in regions of sub-Saharan Africa (SSA), where it is the third most common cancer. Here, we describe whole-exome tumor/normal sequencing and RNA transcriptomic analysis of 59 patients with ESCC in Malawi. ... Full text Link to item Cite

Abstract 1852: Multiple PI3K pathway mutations predominate in low stage endometrial carcinomas

Conference Cancer Research · July 15, 2016 AbstractObjectives: Endometrial cancers (ECs) frequently harbor mutations in PI3K pathway genes. Our objective was to determine the mutation frequency of the PIK3 pathway in the tumors of EC patients prospec ... Full text Cite

An oncogenic Ezh2 mutation induces tumors through global redistribution of histone 3 lysine 27 trimethylation.

Journal Article Nat Med · June 2016 B cell lymphoma and melanoma harbor recurrent mutations in the gene encoding the EZH2 histone methyltransferase (EZH2), but the carcinogenic role of these mutations is unclear. Here we describe a mouse model in which the most common somatic Ezh2 gain-of-fu ... Full text Link to item Cite

Genomic Classification of Cutaneous Melanoma.

Journal Article Cell · June 18, 2015 We describe the landscape of genomic alterations in cutaneous melanomas through DNA, RNA, and protein-based analysis of 333 primary and/or metastatic melanomas from 331 patients. We establish a framework for genomic classification into one of four subtypes ... Full text Link to item Cite

Mutation-specific RAS oncogenicity explains NRAS codon 61 selection in melanoma.

Journal Article Cancer Discov · December 2014 UNLABELLED: NRAS mutation at codons 12, 13, or 61 is associated with transformation; yet, in melanoma, such alterations are nearly exclusive to codon 61. Here, we compared the melanoma susceptibility of an NrasQ61R knock-in allele to similarly designed Kra ... Full text Link to item Cite

Targeted next generation sequencing identifies clinically actionable mutations in patients with melanoma.

Journal Article Pigment Cell Melanoma Res · July 2014 Somatic sequencing of cancers has produced new insight into tumorigenesis, tumor heterogeneity, and disease progression, but the vast majority of genetic events identified are of indeterminate clinical significance. Here, we describe a NextGen sequencing a ... Full text Link to item Cite

Detecting and characterizing circular RNAs.

Journal Article Nat Biotechnol · May 2014 Circular RNA transcripts were first identified in the early 1990s but knowledge of these species has remained limited, as their study through traditional methods of RNA analysis has been difficult. Now, novel bioinformatic approaches coupled with biochemic ... Full text Link to item Cite

Identification of driver genes in hepatocellular carcinoma by exome sequencing.

Journal Article Hepatology · November 2013 UNLABELLED: Genetic alterations in specific driver genes lead to disruption of cellular pathways and are critical events in the instigation and progression of hepatocellular carcinoma (HCC). As a prerequisite for individualized cancer treatment, we sought ... Full text Link to item Cite

Mutations in isocitrate dehydrogenase 1 and 2 occur frequently in intrahepatic cholangiocarcinomas and share hypermethylation targets with glioblastomas.

Journal Article Oncogene · June 20, 2013 Mutations in the genes encoding isocitrate dehydrogenase, IDH1 and IDH2, have been reported in gliomas, myeloid leukemias, chondrosarcomas and thyroid cancer. We discovered IDH1 and IDH2 mutations in 34 of 326 (10%) intrahepatic cholangiocarcinomas. Tumor ... Full text Link to item Cite

Abstract 4598: Identification of driver genes in hepatocellular carcinoma by exome sequencing.

Conference Cancer Research · April 15, 2013 AbstractGenetic alterations in specific driver genes lead to disruption of cellular pathways and are critical events in the instigation and progression of hepatocellular carcinoma. As a prerequisite for indi ... Full text Cite

Abstract 1087: Differential oncogenicity of N-RAS mutations in melanoma.

Conference Cancer Research · April 15, 2013 AbstractIn human cancer, N-RAS mutations resulting in constitutive, oncogenic signaling are predominately localized to codons 12, 13 or 61. Traditionally, activating RAS mutations have been considered oncoge ... Full text Cite

Circular RNAs are abundant, conserved, and associated with ALU repeats.

Journal Article RNA · February 2013 Circular RNAs composed of exonic sequence have been described in a small number of genes. Thought to result from splicing errors, circular RNA species possess no known function. To delineate the universe of endogenous circular RNAs, we performed high-throu ... Full text Link to item Cite

Review: a meta-analysis of GWAS and age-associated diseases.

Journal Article Aging Cell · October 2012 Genome-Wide Association studies (GWAS) offer an unbiased means to understand the genetic basis of traits by identifying single nucleotide polymorphisms (SNPs) linked to causal variants of complex phenotypes. GWAS have identified a host of susceptibility SN ... Full text Link to item Cite

Abstract 1058: Mutations in isocitrate dehydrogenase 1 and 2 are associated with DNA hypermethylation in intrahepatic cholangiocarcinomas

Conference Cancer Research · April 15, 2012 AbstractCholangiocarcinomas are rare but aggressive cancers, with an increasing incidence and a dismal 5-year survival rate of less than 5%. Mutations in the genes encoding isocitrate dehydrogenase, IDH1 and ... Full text Cite

Expression of linear and novel circular forms of an INK4/ARF-associated non-coding RNA correlates with atherosclerosis risk.

Journal Article PLoS Genet · December 2, 2010 Human genome-wide association studies have linked single nucleotide polymorphisms (SNPs) on chromosome 9p21.3 near the INK4/ARF (CDKN2a/b) locus with susceptibility to atherosclerotic vascular disease (ASVD). Although this locus encodes three well-characte ... Full text Link to item Cite

De novo assembly using low-coverage short read sequence data from the rice pathogen Pseudomonas syringae pv. oryzae.

Journal Article Genome Res · February 2009 We developed a novel approach for de novo genome assembly using only sequence data from high-throughput short read sequencing technologies. By combining data generated from 454 Life Sciences (Roche) and Illumina (formerly known as Solexa sequencing) sequen ... Full text Link to item Cite

The tardigrade Hypsibius dujardini, a new model for studying the evolution of development.

Journal Article Dev Biol · December 15, 2007 Studying development in diverse taxa can address a central issue in evolutionary biology: how morphological diversity arises through the evolution of developmental mechanisms. Two of the best-studied developmental model organisms, the arthropod Drosophila ... Full text Link to item Cite

Evolution of genes and genomes on the Drosophila phylogeny.

Journal Article Nature · November 8, 2007 Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ... Full text Link to item Cite

Extending assembly of short DNA sequences to handle error.

Journal Article Bioinformatics · November 1, 2007 UNLABELLED: Inexpensive de novo genome sequencing, particularly in organisms with small genomes, is now possible using several new sequencing technologies. Some of these technologies such as that from Illumina's Solexa Sequencing, produce high genomic cove ... Full text Link to item Cite