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Article ; Online: Labs in the time of COVID: an early-career scientist's view.

Chuang, Ling-Shiang

2020 Volume 13, Issue 6

Abstract: The outbreak of COVID-19 has stalled both the basic, clinical and non-COVID medical research. The scientific community has shown extraordinary flexibility and resilience in responding to the pandemic. However, funding restructuring, risk of infection, ... ...

Abstract	The outbreak of COVID-19 has stalled both the basic, clinical and non-COVID medical research. The scientific community has shown extraordinary flexibility and resilience in responding to the pandemic. However, funding restructuring, risk of infection, cancelation of scientific conferences and delayed experiments have already proven detrimental to the career opportunities of early-career scientists. Moreover, school closures and a lack of systematic support for childcare have been additional challenges for early- and mid-career researchers who have young children. This Editorial describes an early-career researcher's experience and highlights how after efficiently contributing to 'flattening the curve' of COVID-19 infections, the research community has an opportunity for growth and re-structuring.
MeSH term(s)	Betacoronavirus ; Biomedical Research/economics ; COVID-19 ; Child ; Child Care/economics ; Child Care/supply & distribution ; Child, Preschool ; Coronavirus Infections/epidemiology ; Humans ; Medical Laboratory Personnel ; New York City/epidemiology ; Pandemics ; Pneumonia, Viral/epidemiology ; Research Personnel ; SARS-CoV-2
Keywords	covid19
Language	English
Publishing date	2020-06-23
Publishing country	England
Document type	Editorial
ZDB-ID	2451104-3
ISSN	1754-8411 ; 1754-8403
ISSN (online)	1754-8411
ISSN	1754-8403
DOI	10.1242/dmm.046151
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Labs in the time of COVID: an early-career scientist's view

Chuang, Ling-Shiang

Dis. model. mech. (Print)

Abstract	The outbreak of COVID-19 has stalled both the basic, clinical and non-COVID medical research. The scientific community has shown extraordinary flexibility and resilience in responding to the pandemic. However, funding restructuring, risk of infection, cancelation of scientific conferences and delayed experiments have already proven detrimental to the career opportunities of early-career scientists. Moreover, school closures and a lack of systematic support for childcare have been additional challenges for early- and mid-career researchers who have young children. This Editorial describes an early-career researcher's experience and highlights how after efficiently contributing to 'flattening the curve' of COVID-19 infections, the research community has an opportunity for growth and re-structuring.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #703740
Database	COVID19

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Book ; Online: Labs in the time of COVID

Chuang, Ling-shiang

an early-career scientist's view

2020

Abstract: ... ABSTRACT ... The outbreak of COVID-19 has stalled both the basic, clinical and non-COVID medical research. The scientific community has shown extraordinary flexibility and resilience in responding to the pandemic. However, funding restructuring, ...

Abstract	<sec><st>ABSTRACT</st> The outbreak of COVID-19 has stalled both the basic, clinical and non-COVID medical research. The scientific community has shown extraordinary flexibility and resilience in responding to the pandemic. However, funding restructuring, risk of infection, cancelation of scientific conferences and delayed experiments have already proven detrimental to the career opportunities of early-career scientists. Moreover, school closures and a lack of systematic support for childcare have been additional challenges for early- and mid-career researchers who have young children. This Editorial describes an early-career researcher's experience and highlights how after efficiently contributing to ‘flattening the curve’ of COVID-19 infections, the research community has an opportunity for growth and re-structuring. </sec>
Keywords	EDITORIAL ; covid19
Language	English
Publishing date	2020-06-23 00:37:16.0
Publisher	The Company of Biologists Ltd
Publishing country	us
Document type	Book ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Unraveling the Oral-Gut axis: Interconnection between Periodontitis and IBD, Current Challenges, and Future Perspective.

Tanwar, Himanshi / Gnanasekaran, Jeba Mercy / Allison, Devon / Chuang, Ling-Shiang / He, Xuesong / Aimetti, Mario / Baima, Giacomo / Costalonga, Massimo / Cross, Raymond K / Sears, Cynthia / Mehandru, Saurabh / Cho, Judy / Colombel, Jean-Frederic / Raufman, Jean-Pierre / Thumbigere-Math, Vivek

Journal of Crohn's & colitis

2024

Abstract: As the opposite ends of the orodigestive tract, the oral cavity and the intestine share anatomical, microbial, and immunological ties that have bidirectional health implications. A growing body of evidence suggests an interconnection between oral ... ...

Abstract	As the opposite ends of the orodigestive tract, the oral cavity and the intestine share anatomical, microbial, and immunological ties that have bidirectional health implications. A growing body of evidence suggests an interconnection between oral pathologies and Inflammatory Bowel Disease (IBD), implying a shift from the traditional concept of independent diseases to a complex, reciprocal cycle. This review outlines the evidence supporting an "Oral-Gut" axis, marked by a higher prevalence of periodontitis and other oral conditions in IBD patients and vice versa. We present an in-depth examination of the interconnection between oral pathologies and IBD, highlighting the shared microbiological and immunological pathways, and proposing a "multi-hit" hypothesis in the pathogenesis of periodontitis-mediated intestinal inflammation. Furthermore, the review underscores the critical need for a collaborative approach between dentists and gastroenterologists to provide holistic oral-systemic healthcare.
Language	English
Publishing date	2024-02-28
Publishing country	England
Document type	Journal Article
ZDB-ID	2390120-2
ISSN	1876-4479 ; 1873-9946
ISSN (online)	1876-4479
ISSN	1873-9946
DOI	10.1093/ecco-jcc/jjae028
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Article ; Online: Multimodal single-cell analyses reveal mechanisms of perianal fistula in diverse patients with Crohn's disease.

Levantovsky, Rachel M / Tastad, Christopher / Zhang, Jiayu / Gettler, Kyle / Sabic, Ksenija / Werner, Robert / Chasteau, Colleen / Korie, Ujunwa / Paguay, Diana / Bao, Michelle / Han, Huajun / Maskey, Neha / Talware, Sayali / Patel, Manishkumar / Argmann, Carmen / Suarez-Farinas, Mayte / Harpaz, Noam / Chuang, Ling-Shiang / Cho, Judy H

Med (New York, N.Y.)

2024

Abstract: Background: Crohn's disease complicated by perianal fistulae is more prevalent and severe in patients of African ancestry.: Methods: We profiled single cells from diverse patients with Crohn's disease with perianal fistula from colorectal mucosa and ... ...

Abstract	Background: Crohn's disease complicated by perianal fistulae is more prevalent and severe in patients of African ancestry. Methods: We profiled single cells from diverse patients with Crohn's disease with perianal fistula from colorectal mucosa and fistulous tracts. Immunofluorescence was performed to validate predicted cell-cell interactions. Unstimulated monocytes were chronically cultured in diverse cohorts. A subset was analyzed by single-nucleus RNA + ATAC sequencing. Findings: Fistulous tract cells from complete proctectomies demonstrated enrichment of myeloid cells compared to paired rectal tissues. Ligand-receptor analysis highlights myeloid-stromal cross-talk and cellular senescence, with cellular co-localization validated by immunofluorescence. Chitinase-3 like-protein-1 (CHI3L1) is a top upregulated gene in stromal cells from fistulae expressing both destructive and fibrotic gene signatures. Monocyte cultures from patients of African ancestry and controls demonstrated differences in CHI3L1 and oncostatin M (OSM) expression upon differentiation compared to individuals of European ancestry. Activating protein-1 footprints are present in ATAC-seq peaks in stress response genes, including CHI3L1 and OSM; genome-wide chromatin accessibility including JUN footprints was observed, consistent with reported mechanisms of inflammatory memory. Regulon analyses confirm known cell-specific transcription factor regulation and implicate novel ones in fibroblast subsets. All pseudo-bulked clusters demonstrate enrichment of genetic loci, establishing multicellular contributions. In the most significant African American Crohn's genetic locus, upstream of prostaglandin E receptor 4, lymphoid-predominant ATAC-seq peaks were observed, with predicted RORC footprints. Conclusions: Population differences in myeloid-stromal cross-talk implicate fibrotic and destructive fibroblasts, senescence, epigenetic memory, and cell-specific enhancers in perianal fistula pathogenesis. The transcriptomic and epigenetic data provided here may guide optimization of promising mesenchymal stem cell therapies for perianal fistula. Funding: This work was supported by grants U01DK062422, U24DK062429, and R01DK123758.
Language	English
Publishing date	2024-04-18
Publishing country	United States
Document type	Journal Article
ISSN	2666-6340
ISSN (online)	2666-6340
DOI	10.1016/j.medj.2024.03.021
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Article ; Online: Unraveling the Link between Periodontitis and Inflammatory Bowel Disease: Challenges and Outlook.

ArXiv

2023

Abstract: Periodontitis and Inflammatory Bowel Disease (IBD) are chronic inflammatory conditions, characterized by microbial dysbiosis and hyper-immunoinflammatory responses. Growing evidence suggest an interconnection between periodontitis and IBD, implying a ... ...

Abstract	Periodontitis and Inflammatory Bowel Disease (IBD) are chronic inflammatory conditions, characterized by microbial dysbiosis and hyper-immunoinflammatory responses. Growing evidence suggest an interconnection between periodontitis and IBD, implying a shift from the traditional concept of independent diseases to a complex, reciprocal cycle. This review outlines the evidence supporting an "Oral-Gut" axis, marked by a higher prevalence of periodontitis in IBD patients and vice versa. The specific mechanisms linking periodontitis and IBD remain to be fully elucidated, but emerging evidence points to the ectopic colonization of the gut by oral bacteria, which promote intestinal inflammation by activating host immune responses. This review presents an in-depth examination of the interconnection between periodontitis and IBD, highlighting the shared microbiological and immunological pathways, and proposing a "multi-hit" hypothesis in the pathogenesis of periodontitis-mediated intestinal inflammation. Furthermore, the review underscores the critical need for a collaborative approach between dentists and gastroenterologists to provide holistic oral-systemic healthcare.
Language	English
Publishing date	2023-08-19
Publishing country	United States
Document type	Preprint
ISSN	2331-8422
ISSN (online)	2331-8422
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: NOX1 is essential for TNFα-induced intestinal epithelial ROS secretion and inhibits M cell signatures.

Hsu, Nai-Yun / Nayar, Shikha / Gettler, Kyle / Talware, Sayali / Giri, Mamta / Alter, Isaac / Argmann, Carmen / Sabic, Ksenija / Thin, Tin Htwe / Ko, Huai-Bin Mabel / Werner, Robert / Tastad, Christopher / Stappenbeck, Thaddeus / Azabdaftari, Aline / Uhlig, Holm H / Chuang, Ling-Shiang / Cho, Judy H

Gut

2022 Volume 72, Issue 4, Page(s) 654–662

Abstract: Objective: Loss-of-function mutations in genes generating reactive oxygen species (ROS), such as : Design: ROS measurements and single-cell transcriptomics were performed on colonoids stratified by : Results: TNFα induces ROS production more in ... ...

Abstract	Objective: Loss-of-function mutations in genes generating reactive oxygen species (ROS), such as Design: ROS measurements and single-cell transcriptomics were performed on colonoids stratified by Results: TNFα induces ROS production more in NOX1-WT versus NOX1-deficient murine colonoids under a range of Wnt-mediated and Notch-mediated conditions. scRNASeq from inflamed and uninflamed human colitis versus TNFα stimulated, in vitro colonoids defines substantially shared, induced transcription factors; NOX1-deficient colonoids express substantially lower levels of STAT3 (signal transducer and activator of transcription 3), CEBPD (CCAAT enhancer-binding protein delta), Conclusions: NOX1 deficiency plus TNFα stimulation contribute to colitis through dysregulation of the stem cell niche and altered cell differentiation, enhancing basal lymphoplasmacytosis. Our findings prioritise ROS modulation for future therapies.
MeSH term(s)	Mice ; Humans ; Animals ; Reactive Oxygen Species/metabolism ; Tumor Necrosis Factor-alpha/adverse effects ; M Cells ; NADPH Oxidase 1/genetics ; NADPH Oxidase 1/metabolism ; Hydrogen Peroxide/adverse effects ; Colitis/chemically induced ; Inflammatory Bowel Diseases
Chemical Substances	Reactive Oxygen Species ; Tumor Necrosis Factor-alpha ; NADPH Oxidase 1 (EC 1.6.3.-) ; Hydrogen Peroxide (BBX060AN9V) ; NOX1 protein, human (EC 1.6.3.-)
Language	English
Publishing date	2022-10-03
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	80128-8
ISSN	1468-3288 ; 0017-5749
ISSN (online)	1468-3288
ISSN	0017-5749
DOI	10.1136/gutjnl-2021-326305
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Article ; Online: A myeloid-stromal niche and gp130 rescue in NOD2-driven Crohn's disease.

Nayar, Shikha / Morrison, Joshua K / Giri, Mamta / Gettler, Kyle / Chuang, Ling-Shiang / Walker, Laura A / Ko, Huaibin M / Kenigsberg, Ephraim / Kugathasan, Subra / Merad, Miriam / Chu, Jaime / Cho, Judy H

Nature

2021 Volume 593, Issue 7858, Page(s) 275–281

Abstract: Crohn's disease is a chronic inflammatory intestinal disease that is frequently accompanied by aberrant healing and stricturing complications. Crosstalk between activated myeloid and stromal cells is critical in the pathogenicity of Crohn's ... ...

Abstract	Crohn's disease is a chronic inflammatory intestinal disease that is frequently accompanied by aberrant healing and stricturing complications. Crosstalk between activated myeloid and stromal cells is critical in the pathogenicity of Crohn's disease
MeSH term(s)	Alleles ; Animals ; Collagen/metabolism ; Crohn Disease/metabolism ; Cytokine Receptor gp130/antagonists & inhibitors ; Cytokine Receptor gp130/metabolism ; Disease Models, Animal ; Female ; Fibroblasts/cytology ; Fibroblasts/metabolism ; Humans ; Ileitis/metabolism ; Indoles/pharmacology ; Interleukin-11/metabolism ; Lipopolysaccharide Receptors/metabolism ; Macrophages/cytology ; Macrophages/metabolism ; Male ; Myeloid Cells/cytology ; Myeloid Cells/metabolism ; Nod2 Signaling Adaptor Protein/metabolism ; Receptor, Platelet-Derived Growth Factor alpha/metabolism ; STAT3 Transcription Factor/metabolism ; Stromal Cells/cytology ; Stromal Cells/metabolism ; WT1 Proteins/metabolism ; Zebrafish ; Zebrafish Proteins/metabolism
Chemical Substances	Indoles ; Interleukin-11 ; Lipopolysaccharide Receptors ; NOD2 protein, human ; NOD2 protein, zebrafish ; Nod2 Signaling Adaptor Protein ; STAT3 Transcription Factor ; STAT3 protein, human ; WT1 Proteins ; Zebrafish Proteins ; Cytokine Receptor gp130 (133483-10-0) ; Collagen (9007-34-5) ; Receptor, Platelet-Derived Growth Factor alpha (EC 2.7.10.1) ; bazedoxifene (Q16TT9C5BK)
Language	English
Publishing date	2021-03-31
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	120714-3
ISSN	1476-4687 ; 0028-0836
ISSN (online)	1476-4687
ISSN	0028-0836
DOI	10.1038/s41586-021-03484-5
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Article ; Online: Neutralizing Anti-Granulocyte Macrophage-Colony Stimulating Factor Autoantibodies Recognize Post-Translational Glycosylations on Granulocyte Macrophage-Colony Stimulating Factor Years Before Diagnosis and Predict Complicated Crohn's Disease.

Mortha, Arthur / Remark, Romain / Del Valle, Diane Marie / Chuang, Ling-Shiang / Chai, Zhi / Alves, Inês / Azevedo, Catarina / Gaifem, Joana / Martin, Jerome / Petralia, Francesca / Tuballes, Kevin / Barcessat, Vanessa / Tai, Siu Ling / Huang, Hsin-Hui / Laface, Ilaria / Jerez, Yeray Arteaga / Boschetti, Gilles / Villaverde, Nicole / Wang, Mona D /

Korie, Ujunwa M / Murray, Joseph / Choung, Rok-Seon / Sato, Takahiro / Laird, Renee M / Plevy, Scott / Rahman, Adeeb / Torres, Joana / Porter, Chad / Riddle, Mark S / Kenigsberg, Ephraim / Pinho, Salomé S / Cho, Judy H / Merad, Miriam / Colombel, Jean-Frederic / Gnjatic, Sacha

Gastroenterology

2022 Volume 163, Issue 3, Page(s) 659–670

Abstract: Background & aims: Anti-granulocyte macrophage-colony stimulating factor autoantibodies (aGMAbs) are detected in patients with ileal Crohn's disease (CD). Their induction and mode of action during or before disease are not well understood. We aimed to ... ...

Abstract	Background & aims: Anti-granulocyte macrophage-colony stimulating factor autoantibodies (aGMAbs) are detected in patients with ileal Crohn's disease (CD). Their induction and mode of action during or before disease are not well understood. We aimed to investigate the underlying mechanisms associated with aGMAb induction, from functional orientation to recognized epitopes, for their impact on intestinal immune homeostasis and use as a predictive biomarker for complicated CD. Methods: We characterized using enzyme-linked immunosorbent assay naturally occurring aGMAbs in longitudinal serum samples from patients archived before the diagnosis of CD (n = 220) as well as from 400 healthy individuals (matched controls) as part of the US Defense Medical Surveillance System. We used biochemical, cellular, and transcriptional analysis to uncover a mechanism that governs the impaired immune balance in CD mucosa after diagnosis. Results: Neutralizing aGMAbs were found to be specific for post-translational glycosylation on granulocyte macrophage-colony stimulating factor (GM-CSF), detectable years before diagnosis, and associated with complicated CD at presentation. Glycosylation of GM-CSF was altered in patients with CD, and aGMAb affected myeloid homeostasis and promoted group 1 innate lymphoid cells. Perturbations in immune homeostasis preceded the diagnosis in the serum of patients with CD presenting with aGMAb and were detectable in the noninflamed CD mucosa. Conclusions: Anti-GMAbs predict the diagnosis of complicated CD long before the diagnosis of disease, recognize uniquely glycosylated epitopes, and impair myeloid cell and innate lymphoid cell balance associated with altered intestinal immune homeostasis.
MeSH term(s)	Autoantibodies ; Crohn Disease/complications ; Epitopes ; Glycosylation ; Granulocyte-Macrophage Colony-Stimulating Factor/metabolism ; Humans ; Ileal Diseases/complications ; Immunity, Innate ; Lymphocytes ; Macrophages
Chemical Substances	Autoantibodies ; Epitopes ; Granulocyte-Macrophage Colony-Stimulating Factor (83869-56-1)
Language	English
Publishing date	2022-05-24
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	80112-4
ISSN	1528-0012 ; 0016-5085
ISSN (online)	1528-0012
ISSN	0016-5085
DOI	10.1053/j.gastro.2022.05.029
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Article ; Online: Zebrafish modeling of intestinal injury, bacterial exposures and medications defines epithelial

Chuang, Ling-Shiang / Morrison, Joshua / Hsu, Nai-Yun / Labrias, Philippe Ronel / Nayar, Shikha / Chen, Ernie / Villaverde, Nicole / Facey, Jody Ann / Boschetti, Gilles / Giri, Mamta / Castillo-Martin, Mireia / Thin, Tin Htwe / Sharma, Yashoda / Chu, Jaime / Cho, Judy H

Disease models & mechanisms

2019 Volume 12, Issue 8

Abstract: Genome-wide association studies have identified over 200 genomic loci associated with inflammatory bowel disease (IBD). High-effect risk alleles define key roles for genes involved in bacterial response and innate defense. More high- ... ...

Abstract	Genome-wide association studies have identified over 200 genomic loci associated with inflammatory bowel disease (IBD). High-effect risk alleles define key roles for genes involved in bacterial response and innate defense. More high-throughput
MeSH term(s)	Acids/metabolism ; Animals ; Autophagy ; Bacterial Proteins/metabolism ; Dextran Sulfate ; Dinoprostone/metabolism ; Disease Models, Animal ; Enterocytes/metabolism ; Epithelium/pathology ; Humans ; Inflammatory Bowel Diseases/drug therapy ; Inflammatory Bowel Diseases/microbiology ; Inflammatory Bowel Diseases/pathology ; Intestines/injuries ; Intestines/pathology ; Lysosomes/metabolism ; Models, Biological ; Mucins/metabolism ; Mucus/metabolism ; Zebrafish/physiology
Chemical Substances	Acids ; Bacterial Proteins ; Mucins ; Dextran Sulfate (9042-14-2) ; Dinoprostone (K7Q1JQR04M)
Language	English
Publishing date	2019-08-13
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	1754-8411
ISSN (online)	1754-8411
DOI	10.1242/dmm.037432
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