Joshua R. Friedman
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View article: Deep Learning Models Capture Histological Disease Activity in Crohn’s Disease and Ulcerative Colitis with High Fidelity
Deep Learning Models Capture Histological Disease Activity in Crohn’s Disease and Ulcerative Colitis with High Fidelity Open
Background and Aims Histological disease activity in inflammatory bowel disease [IBD] is associated with clinical outcomes and is an important endpoint in drug development. We developed deep learning models for automating histological asse…
View article: A temporal classifier predicts histopathology state and parses acute-chronic phasing in inflammatory bowel disease patients
A temporal classifier predicts histopathology state and parses acute-chronic phasing in inflammatory bowel disease patients Open
Previous studies have conducted time course characterization of murine colitis models through transcriptional profiling of differential expression. We characterize the transcriptional landscape of acute and chronic models of dextran sodium…
View article: Interleukin-22 regulates neutrophil recruitment in ulcerative colitis and is associated with resistance to ustekinumab therapy
Interleukin-22 regulates neutrophil recruitment in ulcerative colitis and is associated with resistance to ustekinumab therapy Open
View article: Biopsy and blood-based molecular biomarker of inflammation in IBD
Biopsy and blood-based molecular biomarker of inflammation in IBD Open
Objective IBD therapies and treatments are evolving to deeper levels of remission. Molecular measures of disease may augment current endpoints including the potential for less invasive assessments. Design Transcriptome analysis on 712 endo…
View article: Cytokine responsive networks in human colonic epithelial organoids unveil a molecular classification of inflammatory bowel disease
Cytokine responsive networks in human colonic epithelial organoids unveil a molecular classification of inflammatory bowel disease Open
View article: Integrative Analysis of the Inflammatory Bowel Disease Serum Metabolome Improves Our Understanding of Genetic Etiology and Points to Novel Putative Therapeutic Targets
Integrative Analysis of the Inflammatory Bowel Disease Serum Metabolome Improves Our Understanding of Genetic Etiology and Points to Novel Putative Therapeutic Targets Open
View article: Molecular Characterization of Limited Ulcerative Colitis Reveals Novel Biology and Predictors of Disease Extension
Molecular Characterization of Limited Ulcerative Colitis Reveals Novel Biology and Predictors of Disease Extension Open
View article: Cytokine Responsive Networks in Human Colonic Epithelial Organoids Unveil a Novel Molecular Stratification of Inflammatory Bowel Disease
Cytokine Responsive Networks in Human Colonic Epithelial Organoids Unveil a Novel Molecular Stratification of Inflammatory Bowel Disease Open
View article: Deep Analysis of the Peripheral Immune System in IBD Reveals New Insight in Disease Subtyping and Response to Monotherapy or Combination Therapy
Deep Analysis of the Peripheral Immune System in IBD Reveals New Insight in Disease Subtyping and Response to Monotherapy or Combination Therapy Open
View article: Intestinal Inflammation Modulates the Expression of ACE2 and TMPRSS2 and Potentially Overlaps With the Pathogenesis of SARS-CoV-2–related Disease
Intestinal Inflammation Modulates the Expression of ACE2 and TMPRSS2 and Potentially Overlaps With the Pathogenesis of SARS-CoV-2–related Disease Open
View article: Relationship Between Combined Histologic and Endoscopic Endpoints and Efficacy of Ustekinumab Treatment in Patients With Ulcerative Colitis
Relationship Between Combined Histologic and Endoscopic Endpoints and Efficacy of Ustekinumab Treatment in Patients With Ulcerative Colitis Open
Data from the UNIFI program of ustekinumab in patients with UC treated with ustekinumab indicated the achievement of histo-endoscopic mucosal healing after induction therapy is associated with lower disease activity at the end of maintenan…
View article: Intestinal inflammation modulates the expression of ACE2 and TMPRSS2 and potentially overlaps with the pathogenesis of SARS-CoV-2 related disease
Intestinal inflammation modulates the expression of ACE2 and TMPRSS2 and potentially overlaps with the pathogenesis of SARS-CoV-2 related disease Open
Immune dysregulation and cytokine release syndrome have emerged as pathological hallmarks of severe Coronavirus Disease 2019 (COVID-19), leading to the evaluation of cytokine antagonists as therapeutic agents. A number of immune-directed t…
View article: Interleukin-22 orchestrates a pathological endoplasmic reticulum stress response transcriptional programme in colonic epithelial cells
Interleukin-22 orchestrates a pathological endoplasmic reticulum stress response transcriptional programme in colonic epithelial cells Open
Objective The functional role of interleukin-22 (IL22) in chronic inflammation is controversial, and mechanistic insights into how it regulates target tissue are lacking. In this study, we evaluated the functional role of IL22 in chronic c…
View article: Single-Cell Analysis of Crohn’s Disease Lesions Identifies a Pathogenic Cellular Module Associated with Resistance to Anti-TNF Therapy
Single-Cell Analysis of Crohn’s Disease Lesions Identifies a Pathogenic Cellular Module Associated with Resistance to Anti-TNF Therapy Open
View article: Effects of Ustekinumab on Histologic Disease Activity in Patients With Crohn’s Disease
Effects of Ustekinumab on Histologic Disease Activity in Patients With Crohn’s Disease Open
In an analysis of data from participants in phase 3 induction and maintenance trials, we found histologic improvement in a greater proportion of patients given ustekinumab vs placebo. The largest improvements occurred in patients who recei…
View article: A negative role for the interleukin-2-inducible T-cell kinase (ITK) in human Foxp3+ TREG differentiation
A negative role for the interleukin-2-inducible T-cell kinase (ITK) in human Foxp3+ TREG differentiation Open
The Tec kinases ITK (interleukin-2-inducible T-cell kinase) and RLK (resting lymphocyte kinase) are critical components of the proximal TCR/CD3 signal transduction machinery, and data in mice suggest that ITK negatively modulates regulator…
View article: OP13 Molecular response to ustekinumab in moderate-to-severe ulcerative colitis by serum protein and biopsy gene expression analysis: Results from the UNIFI Phase 3 induction study
OP13 Molecular response to ustekinumab in moderate-to-severe ulcerative colitis by serum protein and biopsy gene expression analysis: Results from the UNIFI Phase 3 induction study Open
The cytokines IL-12 and IL-23 are elevated in ulcerative colitis (UC) and genetic association suggests that they play causative roles in the disease. Ustekinumab (UST), an anti-IL-12p40 monoclonal antibody that blocks both cytokines, is an…
View article: OP17 A molecular measure of inflammation in IBD patients based on transcriptional profiles from 2495 intestinal biopsies
OP17 A molecular measure of inflammation in IBD patients based on transcriptional profiles from 2495 intestinal biopsies Open
Endoscopy, histology, and biomarker measures of inflammation have limitations of sensitivity, specificity, reproducibility, and range in evaluating inflammatory bowel disease (IBD). We explored whole transcriptome gene expression to define…
View article: DOP71 Effects of ustekinumab induction therapy on endoscopic and histological healing in the UNIFI Phase 3 study in ulcerative colitis
DOP71 Effects of ustekinumab induction therapy on endoscopic and histological healing in the UNIFI Phase 3 study in ulcerative colitis Open
Ustekinumab (UST) is an effective therapy for moderate–severe UC; however, data regarding histological healing and the combination of histological and endoscopic healing (also described as endoscopic improvement in the appearance of the mu…
View article: Gut microbiota density influences host physiology and is shaped by host and microbial factors
Gut microbiota density influences host physiology and is shaped by host and microbial factors Open
To identify factors that regulate gut microbiota density and the impact of varied microbiota density on health, we assayed this fundamental ecosystem property in fecal samples across mammals, human disease, and therapeutic interventions. P…
View article: Low-Dose Interleukin-2 Ameliorates Colitis in a Preclinical Humanized Mouse Model
Low-Dose Interleukin-2 Ameliorates Colitis in a Preclinical Humanized Mouse Model Open
Inflammatory bowel disease (IBD) is associated with immune dysregulation triggered by environmental factors, microbial dysbiosis, and genetical susceptibility. Regulatory T cells (Tregs) are critical in controlling intestinal immune homeos…
View article: Author response: Gut microbiota density influences host physiology and is shaped by host and microbial factors
Author response: Gut microbiota density influences host physiology and is shaped by host and microbial factors Open
View article: A negative role for the interleukin-2-inducible T-cell kinase (ITK) in human Foxp3+ T<sub>REG</sub> differentiation
A negative role for the interleukin-2-inducible T-cell kinase (ITK) in human Foxp3+ T<sub>REG</sub> differentiation Open
The Tec kinases ITK (interleukin-2-inducible T-cell kinase) and RLK (resting lymphocyte kinase) are critical components of the proximal TCR/CD3 signal transduction machinery, and data in mice suggest that ITK negatively regulates T REG dif…
View article: Gut microbiota density influences host physiology and is shaped by host and microbial factors
Gut microbiota density influences host physiology and is shaped by host and microbial factors Open
Summary To identify factors that regulate gut microbiota density and the impact of varied microbiota density on health, we assayed this fundamental ecosystem property in fecal samples across mammals, human disease, and therapeutic interven…
View article: Immune checkpoint inhibitor PD-1 pathway is down-regulated in synovium at various stages of rheumatoid arthritis disease progression
Immune checkpoint inhibitor PD-1 pathway is down-regulated in synovium at various stages of rheumatoid arthritis disease progression Open
Immune checkpoint blockade with therapeutic anti-cytotoxic T lymphocyte-associated antigen (CTLA)-4 (Ipilimumab) and anti-programmed death (PD)-1 (Nivolumab and Pembrolizumab) antibodies alone or in combination has shown remarkable efficac…
View article: P066 INTESTINAL EPITHELIAL MICROVILLI ARE ABNORMAL IN CROHN’S DISEASE
P066 INTESTINAL EPITHELIAL MICROVILLI ARE ABNORMAL IN CROHN’S DISEASE Open
Crohn’s disease (CD) presents as chronic and often progressive intestinal inflammation, but the contributing pathogenic mechanisms are unclear. Our goal was to identify underlying alterations in intestinal host cells that could contribute …
View article: DOP014 Impact of genetic variation on gene and protein expression in Crohn’s disease
DOP014 Impact of genetic variation on gene and protein expression in Crohn’s disease Open
Understanding the genetic landscape of Crohn’s disease (CD) may help shed light on disease aetiology to inform disease understanding and aid biomarker identification. Towards this end, we evaluated the association of genetic polymorphisms …
View article: A functional genomics predictive network model identifies regulators of inflammatory bowel disease
A functional genomics predictive network model identifies regulators of inflammatory bowel disease Open
View article: GI Research Path: From Academia to the Pharmaceutical Industry
GI Research Path: From Academia to the Pharmaceutical Industry Open
View article: Ustekinumab as Induction and Maintenance Therapy for Crohn’s Disease
Ustekinumab as Induction and Maintenance Therapy for Crohn’s Disease Open
BACKGROUND
\nUstekinumab, a monoclonal antibody to the p40 subunit of interleukin-12 and inter-leukin-23, was evaluated as an intravenous induction therapy in two populations with moderately to severely active Crohn’s disease. Ustekinumab …