A5017800643- Inflammatory Bowel Disease
- Immunodeficiency and Autoimmune Disorders
- Radiomics and Machine Learning in Medical Imaging
- Lung Cancer Diagnosis and Treatment
- Immune Cell Function and Interaction
- Microscopic Colitis
- Cancer-related molecular mechanisms research
- Eosinophilic Esophagitis
- Gene expression and cancer classification
- Renal Transplantation Outcomes and Treatments
- T-cell and B-cell Immunology
- Helicobacter pylori-related gastroenterology studies
- Tuberculosis Research and Epidemiology
- Celiac Disease Research and Management
- Bioinformatics and Genomic Networks
- Whipple's Disease and Interleukins
- Cytomegalovirus and herpesvirus research
- Inflammasome and immune disorders
- Organ Transplantation Techniques and Outcomes
- Autoimmune and Inflammatory Disorders Research
- Molecular Biology Techniques and Applications
- IL-33, ST2, and ILC Pathways
- Genetics and Neurodevelopmental Disorders
- Ferroptosis and cancer prognosis
- Autoimmune and Inflammatory Disorders
Children's Hospital of Philadelphia
2015-2025
University of Pennsylvania
2021-2022
Philadelphia University
2022
The Wistar Institute
2011-2018
Drexel University
2010
The Hippo-Yap signaling pathway regulates a number of developmental and adult cellular processes, including cell fate determination, tissue growth, tumorigenesis. Members the scaffold protein angiomotin (Amot) family interact with several Hippo components, Yap (Yes-associated protein), either stimulate or inhibit activity. We used combination genetic, biochemical, transcriptional approaches to assess functional consequences Amot-Yap interaction in mice human cells. Mice liver-specific Amot...
The pleiotropic actions of interleukin-2 (IL-2) are essential for regulation immune responses and maintenance tolerance. IL-2 receptor (IL-2R) is composed IL-2Rα, IL-2Rβ, IL-2Rγ subunits, with defects in IL-2Rα their downstream signaling effectors resulting known primary immunodeficiency disorders. Here, we report the first human defect occurring two infant siblings a homozygous IL2RB mutation WSXWS motif, manifesting as multisystem autoimmunity susceptibility to CMV infection. hypomorphic...
Inflammatory Bowel Disease – comprised of Crohn's and Ulcerative Colitis (UC) - is a complex, multi-factorial inflammatory disorder the gastrointestinal tract. In this study we have explored utility naturally occurring circulating miRNAs as potential blood-based biomarkers for non-invasive prediction UC incidences. Whole genome maps in micro-vesicles, Peripheral Blood Mononuclear Cells platelets been constructed from cohort 20 patients normal individuals. Through Significance Analysis...
Vedolizumab is effective for inducing and maintaining remission in adults with inflammatory bowel disease (IBD); however, there limited pediatric data. This study aimed to describe the adverse events clinical response vedolizumab refractory IBD.Disease activity indices, response, concomitant medication use, were measured over 22 weeks an observational prospective cohort of children IBD who had failed anti-tumor necrosis factor therapy subsequently initiated therapy.Twenty-one subjects, 16...
Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA1) is the EBV-encoded and sequence-specific DNA binding protein required for viral origin episome maintenance during latency. EBNA1 can also bind to numerous sites in cellular genome provide a host cell survival function, but it not yet known how responsible survival. Here, we integrate chromatin immunoprecipitation sequencing (ChIP-Seq) with transcriptome (RNA-Seq) after depletion identify genes directly regulated by that are essential B-cell...
The autoimmune disease systemic lupus erythematosus (SLE) has a modified epigenome with tri-methylation of histone H3 lysine 4 (H3K4me3) at specific loci across the genome. H3K4me3 is canonical chromatin mark active transcription. Recent studies have suggested that breadth an important regulatory role in cell identity. This project examined transcription start sites (TSS) primary monocytes and its association differential gene SLE. Integrative analysis was applied to immunoprecipitation...
Abstract Background Insight into the pathogenesis of very early onset-inflammatory bowel disease (VEO-IBD) has expanded through identification causative monogenic defects detected in a subset patients. However, clinical course this population remains uncertain. The study objective is to determine whether VEO-IBD associated with more severe disease, defined as increased surgical intervention and growth failure, than older pediatric IBD. Secondary outcomes included therapeutic response...
Children with very early onset inflammatory bowel disease [VEO-IBD] represent a unique cohort, often severe phenotype that is refractory to conventional medications, and some cases have underlying primary immunodeficiencies. Previous work has identified distinct histopathological patterns in the gastrointestinal tract patients The aim of this study characterise diagnostic histological findings VEO-IBD as compared older paediatric IBD, determine if there are pathological changes can shed...
Inflammatory bowel disease (IBD) is a complex disorder involving pathogen infection, host immune response, and altered enterocyte physiology. Incidences of IBD are increasing at an alarming rate in developed countries, warranting detailed molecular portrait IBD.We used large-scale data, bioinformatics tools, high-throughput computations to obtain gene microRNA signatures for Crohn's (CD) ulcerative colitis (UC). These were then integrated with systemic literature review draw comprehensive...
Children with very early-onset inflammatory bowel disease (VEO-IBD), those diagnosed at less than 5 years of age, are a unique population. A subset these patients present distinct phenotype and more severe older children adults. Host genetics is thought to play prominent role in this young population, monogenic defects genes related primary immunodeficiencies responsible for the small VEO-IBD. We report child who presented 3 weeks life (VEO-IBD). He had complicated course remained...
The global gene expression analysis of cancer and healthy tissues typically results in large numbers genes that are significantly altered cancer. Such data, however, has been difficult to interpret due the high level variation lists across laboratories small sample sizes used individual studies. In this investigation, we compiled microarray data obtained from same platform family 84 laboratories, resulting a database containing 1,043 tissue samples 4,900 for 13 different types. primary...
Background Co-infection with tuberculosis (TB) is the leading cause of death in HIV-infected individuals. However, diagnosis TB, especially presence an HIV co-infection, can be limiting due to high inaccuracy associated use conventional diagnostic methods. Here we report a gene signature that identify infection patients co-infected as well absence HIV. Methods We analyzed global expression data from peripheral blood mononuclear cell (PBMC) samples were either mono-infected or HIV/TB and used...
Low-dose CT (LDCT) is widely accepted as the preferred method for detecting pulmonary nodules. However, determination of whether a nodule benign or malignant involves either repeated scans invasive procedures that sample lung tissue. Noninvasive methods to assess these nodules are needed reduce unnecessary tests. In this study, we have developed classifier (PNC) using RNA from whole blood collected in RNA-stabilizing PAXgene tubes addresses need. Samples were prospectively high-risk and...
Diverting ileostomy is used as a temporizing therapy in patients with perianal Crohn disease; however, little data exist regarding its use for colonic disease. The primary aim of the present study was to determine role diversion severe refractory inflammatory bowel disease (IBD) pediatric population.Retrospective who underwent diverting at Children's Hospital Philadelphia from 2000 2014 management severe, IBD. Clinical variables were compared 1 year before and after diversion. Surgical...
Donor-derived cell-free DNA (dd-cfDNA) is a noninvasive plasma biomarker to evaluate for transplant allograft rejection. The relationship between infectious complications in kidney allografts and dd-cfDNA has received cursory attention prior publications.Retrospective review of all renal recipients who underwent testing November 2017 August 2019.We report on 7 cases whom infections affecting the transplanted were associated with elevation without concomitant rejection or serum creatinine....
Introduction Therapeutic options are critically needed for children with refractory very early onset inflammatory bowel disease (VEO-IBD). Our aim was to evaluate clinical response canakinumab, an anti-IL-1β monoclonal antibody, in patients VEO-IBD whose phenotype resembles those monogenic autoinflammatory disease. Methods This is a single center retrospective study of (AIP) the absence identified treated canakinumab >6 months. AIP defined as confirmed IBD associated signs systemic...
We previously reported that pegylated IFN-α2a (Peg-IFN-α2a) added to antiretroviral therapy (ART)-suppressed, HIV-infected subjects resulted in plasma HIV control and integrated DNA decrease. now evaluated whether innate NK cell activity or PBMC transcriptional profiles were associated with decreases measures. Human peripheral blood was analyzed prior Peg-IFN-α2a administration (ART, baseline), after 5 wk of ART+Peg-IFN-α2a, 12 monotherapy (primary endpoint). After immune subset frequencies...
Prediction of cancer recurrence in patients with non-small cell lung (NSCLC) currently relies on the assessment clinical characteristics including age, tumor stage, and smoking history. A better prediction early stage poorer survival late is needed to design patient-tailored treatment protocols. We analyzed gene expression RNA from peripheral blood mononuclear cells (PBMC) NSCLC identify signatures predictive overall patient survival. find that PBMC patterns patients, like tumors, have...
// Senthil Kannan 1,2,* , Noor Dawany 2,3,* Raj Kurupati 1 Louise C. Showe 2 and Hildegund C.J. Ertl Gene Therapy Vaccines Program, University of Pennsylvania School Medicine, Philadelphia, Pennsylvania, USA The Wistar Institute Vaccine Center, 3 Department Biomedical Health Informatics, Children’s Hospital * These authors have contributed equally to this work Correspondence to: Ertl, email: Keywords : ASCs, B cells, cell metabolism, programmed death, oxidative phosphorylation,...
Cutaneous T-cell lymphoma (CTCL) is responsive at all stages to immunotherapy. We determined whether a novel agonist for Toll-like receptor (TLR) 7/8 (3M-007) combined with either interferon-γ (IFN-γ) or interleukin-15 (IL-15) would enhance patients' immune responses in vitro. Our data demonstrate that IFN-γ IL-15 combination 007 significantly increases natural killer (NK) cytolytic activity against CTCL tumor cell lines and synergistically induces dendritic cytokines, compared alone....
Very early onset inflammatory bowel disease, diagnosed in children ≤5 years old, can be the initial presentation of some primary immunodeficiencies.In this study, we describe a 17-month-old boy with recurrent infections, growth failure, facial anomalies, and disease. Immune evaluation, whole-exome sequencing, karyotyping, methylation array were performed to evaluate child's constellation symptoms examination findings.Whole-exome sequencing revealed that child was homozygous for novel variant...