Mark D. Gorrell
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View article: Disease-associated genetic variants can cause mutations in tissue-specific protein isoforms
Disease-associated genetic variants can cause mutations in tissue-specific protein isoforms Open
Genetic variants can cause protein-coding mutations that result in disease. Variants are typically interpreted using the reference transcript for a gene. However, most human multi-exon genes encode alternative isoforms. Here, we show that …
View article: Development of a Protocol for Long‐Term Ex Vivo Normothermic Machine Perfusion of Rodent Livers
Development of a Protocol for Long‐Term Ex Vivo Normothermic Machine Perfusion of Rodent Livers Open
Introduction Long‐term normothermic machine perfusion (LT‐NMP) enables the assessment and optimization of livers for days and, potentially, weeks. However, models of LT‐NMP have only been described for human and pig livers, which are resou…
View article: The multifunctional regulatory post-proline protease dipeptidyl peptidase 9 and its inhibitors: new opportunities for therapeutics
The multifunctional regulatory post-proline protease dipeptidyl peptidase 9 and its inhibitors: new opportunities for therapeutics Open
Dipeptidyl Peptidase 9 (DPP9) is a prolyl amino dipeptidylpeptidase that can cut a post-proline peptide bond at the penultimate position at the N-terminus. By removing N-terminal prolines, this intracellular peptidase acts as an upstream r…
View article: Dipeptidyl peptidase 9 (DPP9) depletion from hepatocytes in experimental primary liver cancer
Dipeptidyl peptidase 9 (DPP9) depletion from hepatocytes in experimental primary liver cancer Open
Dipeptidyl peptidase 9 (DPP9) is an indispensable intracellular protease. Among its many molecular functions is suppression of the NLRP1 inflammasome. Inhibitors targeting all four proteases of the DPP4 family, including DPP9, can reduce t…
View article: Development and validation of a novel circulating fibroblast activation protein - based predictive model to improve fibrosis risk stratification in metabolic liver disease population
Development and validation of a novel circulating fibroblast activation protein - based predictive model to improve fibrosis risk stratification in metabolic liver disease population Open
Objective Metabolic fatty liver disease drives chronic liver injury leading to fibrosis. This study aimed to establish a model utilising serum circulating fibroblast activation protein (cFAP) to diagnose advanced fibrosis in patients with …
View article: Dipeptidyl Peptidase 9 (DPP9) Depletion From Hepatocytes in Mice Retards Liver Tumour Growth and Increases Intrahepatic Caspase-1 Activation
Dipeptidyl Peptidase 9 (DPP9) Depletion From Hepatocytes in Mice Retards Liver Tumour Growth and Increases Intrahepatic Caspase-1 Activation Open
Dipeptidyl peptidase 9 (DPP9) is a multifunctional intracellular protease with roles in tumour growth, inflammation and mitochondrial function. We developed a hepatocyte-specific DPP9 knockout mouse (DPP9-KO) to explore DPP9 in a mouse mod…
View article: Bile acids mediate fructose-associated liver tumour growth in mice
Bile acids mediate fructose-associated liver tumour growth in mice Open
High fructose diets are associated with an increased risk of liver cancer. Previous studies in mice suggest increased lipogenesis is a key mechanism linking high fructose diets to liver tumour growth. However, these studies administered fr…
View article: Targeting the SphK1/S1P/PFKFB3 axis suppresses hepatocellular carcinoma progression by disrupting glycolytic energy supply that drives tumor angiogenesis
Targeting the SphK1/S1P/PFKFB3 axis suppresses hepatocellular carcinoma progression by disrupting glycolytic energy supply that drives tumor angiogenesis Open
Background Hepatocellular carcinoma (HCC) remains a leading life-threatening health challenge worldwide, with pressing needs for novel therapeutic strategies. Sphingosine kinase 1 (SphK1), a well-established pro-cancer enzyme, is aberrantl…
View article: Application and Diagnostic Performance of Two-Dimensional Shear Wave Elastography and Liver Fibrosis Scores in Adults with Class 3 Obesity
Application and Diagnostic Performance of Two-Dimensional Shear Wave Elastography and Liver Fibrosis Scores in Adults with Class 3 Obesity Open
There are no ideal non-invasive tests for assessing the severity of liver fibrosis in people with metabolic dysfunction-associated steatotic liver disease (MASLD) and class 3 obesity, where body habitus often makes imaging technically chal…
View article: Supplementary Figures S1-S4 from A Novel Role of Dipeptidyl Peptidase 9 in Epidermal Growth Factor Signaling
Supplementary Figures S1-S4 from A Novel Role of Dipeptidyl Peptidase 9 in Epidermal Growth Factor Signaling Open
Supplementary Figures S1-S4 from A Novel Role of Dipeptidyl Peptidase 9 in Epidermal Growth Factor Signaling
View article: Data from A Novel Role of Dipeptidyl Peptidase 9 in Epidermal Growth Factor Signaling
Data from A Novel Role of Dipeptidyl Peptidase 9 in Epidermal Growth Factor Signaling Open
Dipeptidyl peptidase IV (DPP4), DPP8, DPP9, and fibroblast activation protein (FAP), the four proteases of the DPP4 gene family, have unique peptidase and extra-enzymatic activities that have been implicated in various diseases including c…
View article: Supplementary Figures S1-S4 from A Novel Role of Dipeptidyl Peptidase 9 in Epidermal Growth Factor Signaling
Supplementary Figures S1-S4 from A Novel Role of Dipeptidyl Peptidase 9 in Epidermal Growth Factor Signaling Open
Supplementary Figures S1-S4 from A Novel Role of Dipeptidyl Peptidase 9 in Epidermal Growth Factor Signaling
View article: Data from A Novel Role of Dipeptidyl Peptidase 9 in Epidermal Growth Factor Signaling
Data from A Novel Role of Dipeptidyl Peptidase 9 in Epidermal Growth Factor Signaling Open
Dipeptidyl peptidase IV (DPP4), DPP8, DPP9, and fibroblast activation protein (FAP), the four proteases of the DPP4 gene family, have unique peptidase and extra-enzymatic activities that have been implicated in various diseases including c…
View article: Ablation of sphingosine kinase 2 suppresses fatty liver-associated hepatocellular carcinoma via downregulation of ceramide transfer protein
Ablation of sphingosine kinase 2 suppresses fatty liver-associated hepatocellular carcinoma via downregulation of ceramide transfer protein Open
Hepatocellular carcinoma (HCC) accounts for 90% of primary liver cancer, the third leading cause of cancer-associated death worldwide. With the increasing prevalence of metabolic conditions, non-alcoholic fatty liver disease (NAFLD) is eme…
View article: DPP9 deficiency: An inflammasomopathy that can be rescued by lowering NLRP1/IL-1 signaling
DPP9 deficiency: An inflammasomopathy that can be rescued by lowering NLRP1/IL-1 signaling Open
Dipeptidyl peptidase 9 (DPP9) is a direct inhibitor of NLRP1, but how it affects inflammasome regulation in vivo is not yet established. Here, we report three families with immune-associated defects, poor growth, pancytopenia, and skin pig…
View article: Dipeptidyl peptidase 9 triggers <scp>BRCA2</scp> degradation and promotes <scp>DNA</scp> damage repair
Dipeptidyl peptidase 9 triggers <span>BRCA2</span> degradation and promotes <span>DNA</span> damage repair Open
N‐terminal sequences are important sites for post‐translational modifications that alter protein localization, activity, and stability. Dipeptidyl peptidase 9 (DPP9) is a serine aminopeptidase with the rare ability to cleave off N‐terminal…
View article: Abstract Journal Transplantation Surgery
Abstract Journal Transplantation Surgery Open
Purpose: Split liver transplantation addresses donor shortages by permitting the transplant of two recipients using a single donor liver.Liver splitting can be performed in an ice-bath using the ex-vivo technique, or during the procurement…
View article: Sitagliptin Is More Effective Than Gliclazide in Preventing Pro-Fibrotic and Pro-Inflammatory Changes in a Rodent Model of Diet-Induced Non-Alcoholic Fatty Liver Disease
Sitagliptin Is More Effective Than Gliclazide in Preventing Pro-Fibrotic and Pro-Inflammatory Changes in a Rodent Model of Diet-Induced Non-Alcoholic Fatty Liver Disease Open
A diet-induced non-alcoholic fatty liver disease (NAFLD) model causing obesity in rodents was used to examine whether sitagliptin and gliclazide therapies have similar protective effects on pathological liver change. Methods: Male mice wer…
View article: Targeting CCN2 protects against progressive non-alcoholic steatohepatitis in a preclinical model induced by high-fat feeding and type 2 diabetes
Targeting CCN2 protects against progressive non-alcoholic steatohepatitis in a preclinical model induced by high-fat feeding and type 2 diabetes Open
Type 2 diabetes is an independent risk factor for non-alcoholic steatohepatitis (NASH) progression and its mediators have not been resolved. In this study, a pathogenic role of cellular communication network factor 2 (CCN2) protein in NASH…
View article: Circulating Dipeptidyl Peptidase Activity Is a Potential Biomarker for Inflammatory Bowel Disease
Circulating Dipeptidyl Peptidase Activity Is a Potential Biomarker for Inflammatory Bowel Disease Open
INTRODUCTION: Dipeptidyl peptidase (DPP)-4 is part of a larger family of proteases referred to as DPPs. DPP4 has been suggested as a possible biomarker for inflammatory bowel disease (IBD). Circulating DPP4 (cDPP4) enzyme activity was inve…
View article: Differential Effects of ‘Vaping’ on Lipid and Glucose Profiles and Liver Metabolic Markers in Obese Versus Non-obese Mice
Differential Effects of ‘Vaping’ on Lipid and Glucose Profiles and Liver Metabolic Markers in Obese Versus Non-obese Mice Open
Tobacco smoking increases the risk of metabolic disorders due to the combination of harmful chemicals, whereas pure nicotine can improve glucose tolerance. E-cigarette vapour contains nicotine and some of the harmful chemicals found in cig…
View article: Dipeptidyl Peptidase Inhibition Enhances CD8 T Cell Recruitment and Activates Intrahepatic Inflammasome in a Murine Model of Hepatocellular Carcinoma
Dipeptidyl Peptidase Inhibition Enhances CD8 T Cell Recruitment and Activates Intrahepatic Inflammasome in a Murine Model of Hepatocellular Carcinoma Open
The mRNA expression of the dipeptidyl peptidase 4 (DPP4) gene family is highly upregulated in human hepatocellular carcinoma (HCC) and is associated with poor survival in HCC patients. Compounds that inhibit the DPP4 enzyme family, such as…
View article: DPP9: Comprehensive In Silico Analyses of Loss of Function Gene Variants and Associated Gene Expression Signatures in Human Hepatocellular Carcinoma
DPP9: Comprehensive In Silico Analyses of Loss of Function Gene Variants and Associated Gene Expression Signatures in Human Hepatocellular Carcinoma Open
Dipeptidyl peptidase (DPP) 9, DPP8, DPP4 and fibroblast activation protein (FAP) are the four enzymatically active members of the S9b protease family. Associations of DPP9 with human liver cancer, exonic single nucleotide polymorphisms (SN…
View article: DPP9 deficiency: an Inflammasomopathy which can be rescued by lowering NLRP1/IL-1 signaling
DPP9 deficiency: an Inflammasomopathy which can be rescued by lowering NLRP1/IL-1 signaling Open
Dipeptidyl peptidase 9 (DPP9) is a direct inhibitor of NLRP1, but how it impacts inflammasome regulation in vivo is not yet established. Here, we report two families with immune-associated defects, skin pigmentation abnormalities and neuro…
View article: DPP4 Inhibitor Sitagliptin Enhances Lymphocyte Recruitment and Prolongs Survival in a Syngeneic Ovarian Cancer Mouse Model
DPP4 Inhibitor Sitagliptin Enhances Lymphocyte Recruitment and Prolongs Survival in a Syngeneic Ovarian Cancer Mouse Model Open
Immunity plays a key role in epithelial ovarian cancer (EOC) progression with a well-documented correlation between patient survival and high intratumoral CD8+ to T regulatory cell (Treg) ratios. We previously identified dysregulated DPP4 …
View article: Associations Between DPP9 Expression, Survival and Gene Expression Signature in Human Hepatocellular Carcinoma: Comprehensive In Silico Analyses
Associations Between DPP9 Expression, Survival and Gene Expression Signature in Human Hepatocellular Carcinoma: Comprehensive In Silico Analyses Open
Dipeptidyl peptidase (DPP) 9, DPP8, DPP4 and fibroblast activation protein (FAP) are the four enzymatically active members of the S9b protease family. Associations of DPP9 with human liver cancer, exonic single nucleotide polymorphisms (SN…
View article: A Novel Purification Procedure for Active Recombinant Human DPP4 and the Inability of DPP4 to Bind SARS-CoV-2
A Novel Purification Procedure for Active Recombinant Human DPP4 and the Inability of DPP4 to Bind SARS-CoV-2 Open
Proteases catalyse irreversible posttranslational modifications that often alter a biological function of the substrate. The protease dipeptidyl peptidase 4 (DPP4) is a pharmacological target in type 2 diabetes therapy primarily because it…
View article: A Novel Purification Procedure for Active Recombinant Human DPP4 and the Inability of DPP4 to Bind SARS-CoV-2
A Novel Purification Procedure for Active Recombinant Human DPP4 and the Inability of DPP4 to Bind SARS-CoV-2 Open
Proteases catalyse irreversible posttranslational modifications that often alter a biological function of the substrate. The protease dipeptidyl peptidase 4 (DPP4) is a pharmacological target in type 2 diabetes therapy primarily because it…
View article: Hypoxia Regulates DPP4 Expression, Proteolytic Inactivation, and Shedding from Ovarian Cancer Cells
Hypoxia Regulates DPP4 Expression, Proteolytic Inactivation, and Shedding from Ovarian Cancer Cells Open
The treatment of ovarian cancer has not significantly changed in decades and it remains one of the most lethal malignancies in women. The serine protease dipeptidyl peptidase 4 (DPP4) plays key roles in metabolism and immunity, and its exp…
View article: A Novel Purification Procedure for Active Recombinant Human DPP4 and the Inability of DPP4 to Bind SARS-CoV-2
A Novel Purification Procedure for Active Recombinant Human DPP4 and the Inability of DPP4 to Bind SARS-CoV-2 Open
Proteases catalyse irreversible posttranslational modifications that often alter a biological function of the substrate. The protease dipeptidyl peptidase 4 (DPP4) is a pharmacological target in type 2 diabetes therapy primarily because it…