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MULTICENTER STUDY
Amanda M Johnson, Maria Barsky, Waseem Ahmed, Samantha Zullow, Jonathan Galati, Vipul Jairath, Neeraj Narula, Farhad Peerani, Benjamin H Click, Elliot S Coburn, ThucNhi Tran Dang, Stephanie Gold, Manasi Agrawal, Rajat Garg, Manik Aggarwal, Danah Mohammad, Brendan Halloran, Gursimran S Kochhar, Hannah Todorowski, Nabeeha Mohy Ud Din, James Izanec, Amanda Teeple, Chris Gasink, Erik Muser, Zhijie Ding, Arun Swaminath, Komal Lakhani, Dan Hogan, Samit Datta, Ryan C Ungaro, Brigid S Boland, Matthew Bohm, Monika Fischer, Sashidhar Sagi, Anita Afzali, Thomas Ullman, Garrett Lawlor, Daniel C Baumgart, Shannon Chang, David Hudesman, Dana Lukin, Ellen J Scherl, Jean-Frederic Colombel, Bruce E Sands, Corey A Siegel, Miguel Regueiro, William J Sandborn, David Bruining, Sunanda Kane, Edward V Loftus, Parambir S Dulai
INTRODUCTION: We evaluated the real-world effectiveness and safety of ustekinumab (UST) in patients with Crohn's disease (CD). METHODS: This study used a retrospective, multicenter, multinational consortium of UST-treated CD patients. Data included patient demographics, disease phenotype, disease activity, treatment history, and concomitant medications. Cumulative rates of clinical, steroid-free, endoscopic, and radiographic remissions were assessed using time-to-event analysis, and clinical predictors were assessed by using multivariate Cox proportional hazard analyses...
February 1, 2023: American Journal of Gastroenterology
#2
JOURNAL ARTICLE
Tomomi Tadokoro, Keisuke Tanaka, Shun Osakabe, Mimoko Kato, Hisato Kobayashi, Brigid L M Hogan, Hideki Taniguchi
The tracheal basal cells (BCs) function as stem cells to maintain the epithelium in steady state and repair it after injury. The airway is surrounded by cartilage ventrolaterally and smooth muscle dorsally. Lineage tracing using Krt5-CreER shows dorsal BCs produce more, larger, clones than ventral BCs. Large clones were found between cartilage and smooth muscle where subpopulation of dorsal BCs exists. Three-dimensional organoid culture of BCs demonstrated that dorsal BCs show higher colony forming efficacy to ventral BCs...
August 16, 2021: Biology Open
#3
Brigid Hogan, Purushothama Rao Tata
No abstract text is available yet for this article.
July 25, 2019: Nature Cell Biology
#4
EDITORIAL
Ruth Lehmann, Connie M Lee, Erika C Shugart, Marta Benedetti, R Alta Charo, Zev Gartner, Brigid Hogan, Jürgen Knoblich, Celeste M Nelson, Kevin M Wilson
Organoids derived from stem cells or tissues in culture can develop into structures that resemble the in vivo anatomy and physiology of intact organs. Human organoid cultures provide the potential to study human development and model disease processes with the same scrutiny and depth of analysis customary for research with nonhuman model organisms. Resembling the complexity of the actual tissue or organ, patient-derived human organoid studies may accelerate medical research, creating new opportunities for tissue engineering and regenerative medicine, generating knowledge and tools for preclinical studies, including drug development and testing...
May 1, 2019: Molecular Biology of the Cell
#5
JOURNAL ARTICLE
Hiroaki Katsura, Yoshihiko Kobayashi, Purushothama Rao Tata, Brigid L M Hogan
Inflammatory responses are known to facilitate tissue recovery following injury. However, the precise mechanisms that enhance lung alveolar regeneration remain unclear. Here, using an organoid-based screening assay, we find that interleukin-1 (IL-1) and tumor necrosis factor α (TNFα) enhance the proliferation of AEC2s while maintaining their differentiation capacity. Furthermore, we find that expression of IL-1β and TNFα are induced in the AEC2 niche following influenza-induced injury in vivo, and lineage tracing analysis revealed that surviving AEC2s around the damaged area contribute to alveolar regeneration...
April 9, 2019: Stem Cell Reports
#6
REVIEW
N Ray Dunn, Brigid L M Hogan
The historic town of Taos, New Mexico, with its rich multicultural history of art and craft, was the site of the second Keystone Symposium on 'Endoderm Development and Disease', which was held in February 2018. The theme of the meeting was 'Cross-Organ Comparison and Interplay', emphasizing an integrative and multisystem approach to the broad topics of organ physiology, homeostasis, repair, regeneration and disease. As we review here, participants shared their recent discoveries and discussed how new technologies developed in one organ system might be applied to answer crucial questions in another...
August 16, 2018: Development
#7
JOURNAL ARTICLE
Mei-I Chung, Brigid L M Hogan
The alveolar region of the lung is composed of two major epithelial cell types; cuboidal Type 2 cells (AT2s), that produce surfactant proteins, and large, thin, Type1 cells (AT1s), specialized for efficient gas exchange. AT1s cover more than 95% of the alveolar surface and so constitute a major barrier to the entry of pathogenic agents. Relatively few genetic tools are available for studying the development of AT1s, the function of gene expressed in them, and the effect of specifically killing them in vivo in the adult lung...
July 16, 2018: American Journal of Respiratory Cell and Molecular Biology
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JOURNAL ARTICLE
Brigid Hogan
New England Journal of Medicine, Volume 378, Issue 25, Page 2439-2440, June 2018.
June 21, 2018: New England Journal of Medicine
#9
JOURNAL ARTICLE
Mei-I Chung, Melissa Bujnis, Christina E Barkauskas, Yoshihiko Kobayashi, Brigid L M Hogan
The bone morphogenetic protein (BMP) signaling pathway, including antagonists, functions in lung development and regeneration of tracheal epithelium from basal stem cells. Here, we explore its role in the alveolar region, where type 2 epithelial cells (AT2s) and Pdgfrα+ type 2-associated stromal cells (TASCs) are components of the stem cell niche. We use organoids and in vivo alveolar regrowth after pneumonectomy (PNX) - a process that requires proliferation of AT2s and differentiation into type 1 cells (AT1s)...
May 11, 2018: Development
#10
COMMENT
Brigid L M Hogan
In this issue of Developmental Cell, Tang et al. (2018) and Li et al. (2018) combine genetic manipulation, mechanical perturbation, and live imaging to show how mechanical forces and local growth factors intersect to influence epithelial behavior and cell fate specification within the developing lung.
February 5, 2018: Developmental Cell
#11
REVIEW
Christina E Barkauskas, Mei-I Chung, Bryan Fioret, Xia Gao, Hiroaki Katsura, Brigid L M Hogan
Lungs are composed of a system of highly branched tubes that bring air into the alveoli, where gas exchange takes place. The proximal and distal regions of the lung contain epithelial cells specialized for different functions: basal, secretory and ciliated cells in the conducting airways and type II and type I cells lining the alveoli. Basal, secretory and type II cells can be grown in three-dimensional culture, with or without supporting stromal cells, and under these conditions they give rise to self-organizing structures known as organoids...
March 15, 2017: Development
#12
JOURNAL ARTICLE
BMP signaling and cellular dynamics during regeneration of airway epithelium from basal progenitors.
Tomomi Tadokoro, Xia Gao, Charles C Hong, Danielle Hotten, Brigid L M Hogan
The pseudostratified epithelium of the lung contains ciliated and secretory luminal cells and basal stem/progenitor cells. To identify signals controlling basal cell behavior we screened factors that alter their self-renewal and differentiation in a clonal organoid (tracheosphere) assay. This revealed that inhibitors of the canonical BMP signaling pathway promote proliferation but do not affect lineage choice, whereas exogenous Bmp4 inhibits proliferation and differentiation. We therefore followed changes in BMP pathway components in vivo in the mouse trachea during epithelial regeneration from basal cells after injury...
March 1, 2016: Development
#13
JOURNAL ARTICLE
Xia Gao, Aman S Bali, Scott H Randell, Brigid L M Hogan
Pseudostratified airway epithelium of the lung is composed of polarized ciliated and secretory cells maintained by basal stem/progenitor cells. An important question is how lineage choice and differentiation are coordinated with apical-basal polarity and epithelial morphogenesis. Our previous studies indicated a key integrative role for the transcription factor Grainyhead-like 2 (Grhl2). In this study, we present further evidence for this model using conditional gene deletion during the regeneration of airway epithelium and clonal organoid culture...
November 9, 2015: Journal of Cell Biology
#14
Brigid Hogan, Catarina Vicente
Brigid Hogan is a developmental biologist who has worked extensively on the early stages of mouse development and is now unravelling the mysteries of lung organogenesis. She is the George Barth Geller Professor and Chair of the Department of Cell Biology at Duke University Medical Center. Brigid is also the winner of the 2015 Society for Developmental Biology (SDB) Lifetime Achievement Award.
July 15, 2015: Development
#15
JOURNAL ARTICLE
Rajan Jain, Christina E Barkauskas, Norifumi Takeda, Emily J Bowie, Haig Aghajanian, Qiaohong Wang, Arun Padmanabhan, Lauren J Manderfield, Mudit Gupta, Deqiang Li, Li Li, Chinmay M Trivedi, Brigid L M Hogan, Jonathan A Epstein
The plasticity of differentiated cells in adult tissues undergoing repair is an area of intense research. Pulmonary alveolar type II cells produce surfactant and function as progenitors in the adult, demonstrating both self-renewal and differentiation into gas exchanging type I cells. In vivo, type I cells are thought to be terminally differentiated and their ability to give rise to alternate lineages has not been reported. Here we show that Hopx becomes restricted to type I cells during development. However, unexpectedly, lineage-labelled Hopx(+) cells both proliferate and generate type II cells during adult alveolar regrowth following partial pneumonectomy...
2015: Nature Communications
#16
JOURNAL ARTICLE
Jonathan K Alder, Christina E Barkauskas, Nathachit Limjunyawong, Susan E Stanley, Frant Kembou, Rubin M Tuder, Brigid L M Hogan, Wayne Mitzner, Mary Armanios
Telomere syndromes have their most common manifestation in lung disease that is recognized as idiopathic pulmonary fibrosis and emphysema. In both conditions, there is loss of alveolar integrity, but the underlying mechanisms are not known. We tested the capacity of alveolar epithelial and stromal cells from mice with short telomeres to support alveolar organoid colony formation and found that type 2 alveolar epithelial cells (AEC2s), the stem cell-containing population, were limiting. When telomere dysfunction was induced in adult AEC2s by conditional deletion of the shelterin component telomeric repeat-binding factor 2, cells survived but remained dormant and showed all the hallmarks of cellular senescence...
April 21, 2015: Proceedings of the National Academy of Sciences of the United States of America
#17
JOURNAL ARTICLE
Xia Xu, Lingling Huang, Christopher Futtner, Brian Schwab, Rishi R Rampersad, Yun Lu, Thomas A Sporn, Brigid L M Hogan, Mark W Onaitis
Cell type-specific conditional activation of oncogenic K-Ras is a powerful tool for investigating the cell of origin of adenocarcinomas in the mouse lung. Our previous studies showed that K-Ras activation with a CC10(Scgb1a1)-CreER driver leads to adenocarcinoma in a subset of alveolar type II cells and hyperplasia in the bronchioalveolar duct region. However, no tumors develop in the bronchioles, although recombination occurs throughout this region. To explore underlying mechanisms, we simultaneously modulated either Notch signaling or Sox2 levels in the CC10+ cells along with activation of K-Ras...
September 1, 2014: Genes & Development
#18
JOURNAL ARTICLE
Tomomi Tadokoro, Yang Wang, Larry S Barak, Yushi Bai, Scott H Randell, Brigid L M Hogan
The pseudostratified airway epithelium of the lung contains a balanced proportion of multiciliated and secretory luminal cells that are maintained and regenerated by a population of basal stem cells. However, little is known about how these processes are modulated in vivo, and about the potential role of cytokine signaling between stem and progenitor cells and their niche. Using a clonal 3D organoid assay, we found that IL-6 stimulated, and Stat3 inhibitors reduced, the generation of ciliated vs. secretory cells from basal cells...
September 2, 2014: Proceedings of the National Academy of Sciences of the United States of America
#19
REVIEW
Brigid L M Hogan, Christina E Barkauskas, Harold A Chapman, Jonathan A Epstein, Rajan Jain, Connie C W Hsia, Laura Niklason, Elizabeth Calle, Andrew Le, Scott H Randell, Jason Rock, Melinda Snitow, Matthew Krummel, Barry R Stripp, Thiennu Vu, Eric S White, Jeffrey A Whitsett, Edward E Morrisey
Respiratory disease is the third leading cause of death in the industrialized world. Consequently, the trachea, lungs, and cardiopulmonary vasculature have been the focus of extensive investigations. Recent studies have provided new information about the mechanisms driving lung development and differentiation. However, there is still much to learn about the ability of the adult respiratory system to undergo repair and to replace cells lost in response to injury and disease. This Review highlights the multiple stem/progenitor populations in different regions of the adult lung, the plasticity of their behavior in injury models, and molecular pathways that support homeostasis and repair...
August 7, 2014: Cell Stem Cell
#20
JOURNAL ARTICLE
Carolien Wansleeben, Emily Bowie, Danielle F Hotten, Yen-Rei A Yu, Brigid L M Hogan
We report here senescent changes in the structure and organization of the mucociliary pseudostratified epithelium of the mouse trachea and main stem bronchi. We confirm previous reports of the gradual appearance of age-related, gland-like structures (ARGLS) in the submucosa, especially in the intercartilage regions and carina. Immunohistochemistry shows these structures contain ciliated and secretory cells and Krt5+ basal cells, but not the myoepithelial cells or ciliated ducts typical of normal submucosal glands...
2014: PloS One
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