8 results on '"Judith Kelsen"'
Search Results
2. P623: Cytogenetic findings in a clinical next generation sequencing panel for very early onset inflammatory bowel disease
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Hadia Hijazi, Tamara Luke, Kieran Pechter, Archana Tare, Kajia Cao, Laura Conlin, Judith Kelsen, Nancy Spinner, and Yavuz Bayram
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Genetics ,QH426-470 ,Medicine - Published
- 2024
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3. Isolation of Epithelial and Stromal Cells from Colon Tissues in Homeostasis and Under Inflammatory Conditions
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Clara Morral, Reem Ghinnagow, Tatiana Karakasheva, Yusen Zhou, Anusha Thadi, Ning Li, Benjamin Yoshor, Gloria Soto, Chia- Chen, Daniel Aleynick, Sarah Weinbrom, MaryKate Fulton, Yasin Uzun, Meenakshi Bewtra, Judith Kelsen, Chris Lengner, Kai Tan, Andy Minn, and Kathryn Hamilton
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Biology (General) ,QH301-705.5 - Abstract
Inflammation of the gastrointestinal tract is a prevalent pathology in diseases such as inflammatory bowel disease (IBD). Currently, there are no therapies to prevent IBD, and available therapies to treat IBD are often sub-optimal. Thus, an unmet need exists to better understand the molecular mechanisms underlying intestinal tissue responses to damage and regeneration. The recent development of single-cell RNA (sc-RNA) sequencing-based techniques offers a unique opportunity to shed light on novel signaling pathways and cellular states that govern tissue adaptation or maladaptation across a broad spectrum of diseases. These approaches require the isolation of high-quality cells from tissues for downstream transcriptomic analyses. In the context of intestinal biology, there is a lack of protocols that ensure the isolation of epithelial and non-epithelial compartments simultaneously with high-quality yield. Here, we report two protocols for the isolation of epithelial and stromal cells from mouse and human colon tissues under inflammatory conditions. Specifically, we tested the feasibility of the protocols in a mouse model of dextran sodium sulfate (DSS)-induced colitis and in human biopsies from Crohn’s patients. We performed sc-RNA sequencing analysis and demonstrated that the protocol preserves most of the epithelial and stromal cell types found in the colon. Moreover, the protocol is suitable for immunofluorescence staining of surface markers for epithelial, stromal, and immune cell lineages for flow cytometry analyses. This optimized protocol will provide a new resource for scientists to study complex tissues such as the colon in the context of tissue damage and regeneration.Key features• This protocol allows the isolation of epithelial and stromal cells from colon tissues.• The protocol has been optimized for tissues under inflammatory conditions with compromised cell viability.• This protocol is suitable for experimental mouse models of colon inflammation and human biopsies.Graphical overviewGraphical representation of the main steps for the processing of colon tissue from dextran sodium sulfate (DSS)-treated mice (upper panel) and frozen biopsies from Crohn’s patients (lower panel)
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- 2023
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4. P269: Essential role of genetic counseling in a multidisciplinary immune dysregulation program
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Anna Platt, Hamid Bassiri, Edward Behrens, Scott Canna, Kandace Gollomp, Judith Kelsen, Michele Lambert, Whitney Petrosa, Neil Romberg, Alix Seif, Kathleen Sullivan, and David Teachey
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Genetics ,QH426-470 ,Medicine - Published
- 2023
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5. Very early-onset inflammatory bowel disease: Novel description in glycogen storage disease type Ia
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William B. Hannah, Ricardo C. Ong, Margarita Nieto Moreno, Surekha Pendyal, Monica Abdelmalak, Judith Kelsen, Nancy M. McGreal, and Priya S. Kishnani
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Glycogen storage disease type 1a ,Very early-onset inflammatory bowel ,Medicine (General) ,R5-920 ,Biology (General) ,QH301-705.5 - Abstract
Although inflammatory bowel disease is a well-described feature of glycogen storage disease type Ib, it has been reported in only a small number of individuals with glycogen storage disease type Ia (GSDIa). We describe, to our knowledge, the first patient with GSDIa and very early-onset inflammatory bowel disease (VEO-IBD). Larger studies are needed to better understand this possible association, elucidate the mechanism of VEO-IBD in GSDIa, and inform management.
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- 2022
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6. T cell dynamics and response of the microbiota after gene therapy to treat X-linked severe combined immunodeficiency
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Erik L. Clarke, A. Jesse Connell, Emmanuelle Six, Nadia A. Kadry, Arwa A. Abbas, Young Hwang, John K. Everett, Casey E. Hofstaedter, Rebecca Marsh, Myriam Armant, Judith Kelsen, Luigi D. Notarangelo, Ronald G. Collman, Salima Hacein-Bey-Abina, Donald B. Kohn, Marina Cavazzana, Alain Fischer, David A. Williams, Sung-Yun Pai, and Frederic D. Bushman
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Medicine ,Genetics ,QH426-470 - Abstract
Abstract Background Mutation of the IL2RG gene results in a form of severe combined immune deficiency (SCID-X1), which has been treated successfully with hematopoietic stem cell gene therapy. SCID-X1 gene therapy results in reconstitution of the previously lacking T cell compartment, allowing analysis of the roles of T cell immunity in humans by comparing before and after gene correction. Methods Here we interrogate T cell reconstitution using four forms of high throughput analysis. (1) Estimation of the numbers of transduced progenitor cells by monitoring unique positions of integration of the therapeutic gene transfer vector. (2) Estimation of T cell population structure by sequencing of the recombined T cell receptor (TCR) beta locus. (3) Metagenomic analysis of microbial populations in oropharyngeal, nasopharyngeal, and gut samples. (4) Metagenomic analysis of viral populations in gut samples. Results Comparison of progenitor and mature T cell populations allowed estimation of a minimum number of cell divisions needed to generate the observed populations. Analysis of microbial populations showed the effects of immune reconstitution, including normalization of gut microbiota and clearance of viral infections. Metagenomic analysis revealed enrichment of genes for antibiotic resistance in gene-corrected subjects relative to healthy controls, likely a result of higher healthcare exposure. Conclusions This multi-omic approach enables the characterization of multiple effects of SCID-X1 gene therapy, including T cell repertoire reconstitution, estimation of numbers of cell divisions between progenitors and daughter T cells, normalization of the microbiome, clearance of microbial pathogens, and modulations in antibiotic resistance gene levels. Together, these results quantify several aspects of the long-term efficacy of gene therapy for SCID-X1. This study includes data from ClinicalTrials.gov numbers NCT01410019, NCT01175239, and NCT01129544.
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- 2018
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7. Optimizing methods and dodging pitfalls in microbiome research
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Dorothy Kim, Casey E. Hofstaedter, Chunyu Zhao, Lisa Mattei, Ceylan Tanes, Erik Clarke, Abigail Lauder, Scott Sherrill-Mix, Christel Chehoud, Judith Kelsen, Máire Conrad, Ronald G. Collman, Robert Baldassano, Frederic D. Bushman, and Kyle Bittinger
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Metagenomics ,16S rRNA gene ,Shotgun metagenomics ,Environmental contamination ,Methods ,Study design ,Microbial ecology ,QR100-130 - Abstract
Abstract Research on the human microbiome has yielded numerous insights into health and disease, but also has resulted in a wealth of experimental artifacts. Here, we present suggestions for optimizing experimental design and avoiding known pitfalls, organized in the typical order in which studies are carried out. We first review best practices in experimental design and introduce common confounders such as age, diet, antibiotic use, pet ownership, longitudinal instability, and microbial sharing during cohousing in animal studies. Typically, samples will need to be stored, so we provide data on best practices for several sample types. We then discuss design and analysis of positive and negative controls, which should always be run with experimental samples. We introduce a convenient set of non-biological DNA sequences that can be useful as positive controls for high-volume analysis. Careful analysis of negative and positive controls is particularly important in studies of samples with low microbial biomass, where contamination can comprise most or all of a sample. Lastly, we summarize approaches to enhancing experimental robustness by careful control of multiple comparisons and to comparing discovery and validation cohorts. We hope the experimental tactics summarized here will help researchers in this exciting field advance their studies efficiently while avoiding errors.
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- 2017
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8. 2092 A multicenter study of fecal microbiota transplantation for Clostridium difficile infection in children
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Maribeth R. Nicholson, Erin Alexander, Mark Bartlett, Penny Becker, Zev Davidovics, Elizabeth E. Knackstedt, Michael Docktor, Michael Dole, Grace Felix, Jonathan Gisser, Suchitra Hourigan, Kyle Jensen, Jess Kaplan, Judith Kelsen, Melissa Kennedy, Sahil Khanna, McKenzie Leier, Jeffery Lewis, Ashley Lodarek, Sonia Michail, Paul Mitchell, Maria Oliva‐Hemker, Tiffany Patton, Karen Queliza, Namita Singh, Aliza Solomon, David Suskind, Steven Werlin, Richard Kellermayer, and Stacy Kahn
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Medicine - Abstract
OBJECTIVES/SPECIFIC AIMS: Clostridium difficile infection (CDI) is the most common cause of antibiotic-associated diarrhea and an increasingly common infection in children in both hospital and community settings. Between 20% and 30% of pediatric patients will have a recurrence of symptoms in the days to weeks following an initial infection. Multiple recurrences have been successfully treated with fecal microbiota transplantation (FMT), though the body of evidence in pediatric patients is limited primarily to case reports and case series. The goal of our study was to better understand practices, success, and safety of FMT in children as well as identify risk factors associated with a failed FMT in our pediatric patients. METHODS/STUDY POPULATION: This multicenter retrospective analysis included 373 patients who underwent FMT for CDI between January 1, 2006 and January 1, 2017 from 18 pediatric centers. Demographics, baseline characteristics, FMT practices, C. difficile outcomes, and post-FMT complications were collected through chart abstraction. Successful FMT was defined as no recurrence of CDI within 60 days after FMT. Of the 373 patients in the cohort, 342 had known outcome data at two months post-FMT and were included in the primary analysis evaluating risk factors for recurrence post-FMT. An additional six patients who underwent FMT for refractory CDI were excluded from the primary analysis. Unadjusted analysis was performed using Wilcoxon rank-sum test, Pearson χ2 test, or Fisher exact test where appropriate. Stepwise logistic regression was utilized to determine independent predictors of success. RESULTS/ANTICIPATED RESULTS: The median age of included patients was 10 years (IQR; 3.0, 15.0) and 50% of patients were female. The majority of the cohort was White (89.0%). Comorbidities included 120 patients with inflammatory bowel disease (IBD) and 14 patients who had undergone a solid organ or stem cell transplantation. Of the 336 patients with known outcomes at two months, 272 (81%) had a successful outcome. In the 64 (19%) patients that did have a recurrence, 35 underwent repeat FMT which was successful in 20 of the 35 (57%). The overall success rate of FMT in preventing further episodes of CDI in the cohort with known outcome data was 87%. Unadjusted predictors of a primary FMT response are summarized. Based on stepwise logistic regression modeling, the use of fresh stool, FMT delivery via colonoscopy, the lack of a feeding tube, and a lower number of CDI episodes before undergoing FMT were independently associated with a successful outcome. There were 20 adverse events in the cohort assessed to be related to FMT, 6 of which were felt to be severe. There were no deaths assessed to be related to FMT in the cohort. DISCUSSION/SIGNIFICANCE OF IMPACT: The overall success of FMT in pediatric patients with recurrent or severe CDI is 81% after a single FMT. Children without a feeding tube, who receive an early FMT, FMT with fresh stool, or FMT via colonoscopy are less likely to have a recurrence of CDI in the 2 months following FMT. This is the first large study of FMT for CDI in a pediatric cohort. These findings, if confirmed by additional prospective studies, will support alterations in the practice of FMT in children.
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- 2018
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