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Brigid Hogan

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
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
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
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
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
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
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
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
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
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
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
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
Christina E Barkauskas, Michael J Cronce, Craig R Rackley, Emily J Bowie, Douglas R Keene, Barry R Stripp, Scott H Randell, Paul W Noble, Brigid L M Hogan
Gas exchange in the lung occurs within alveoli, air-filled sacs composed of type 2 and type 1 epithelial cells (AEC2s and AEC1s), capillaries, and various resident mesenchymal cells. Here, we use a combination of in vivo clonal lineage analysis, different injury/repair systems, and in vitro culture of purified cell populations to obtain new information about the contribution of AEC2s to alveolar maintenance and repair. Genetic lineage-tracing experiments showed that surfactant protein C-positive (SFTPC-positive) AEC2s self renew and differentiate over about a year, consistent with the population containing long-term alveolar stem cells...
July 2013: Journal of Clinical Investigation
Carolien Wansleeben, Christina E Barkauskas, Jason R Rock, Brigid L M Hogan
The lung has vital functions in gas exchange and immune defense. To fulfill these functions the cellular composition and complex three-dimensional organization of the organ must be maintained for a lifetime. Cell turnover in the adult lung is normally low. However, in response to cellular injury by agents such as infection, toxic compounds, and irradiation there is rapid proliferation and differentiation of endogenous stem and progenitor cells to repair and regenerate the damaged tissue. In the mouse, different populations of epithelial progenitor cells have been identified in different regions of the respiratory system: basal cells in the proximal tracheobronchial region and submucosal glands, and secretory cells in the conducting airways and bronchioalveolar duct junction...
January 2013: Wiley Interdisciplinary Reviews. Developmental Biology
Emily G O'Koren, Brigid L M Hogan, Michael Dee Gunn
Bronchiolitis obliterans (BO) is a major cause of chronic airway dysfunction after toxic chemical inhalation. The pathophysiology of BO is not well understood, but epithelial cell injury has been closely associated with the development of fibrotic lesions in human studies and in animal models of both toxin-induced and transplant-induced BO. However, whereas almost all cases and models of BO include epithelial injury, not all instances of epithelial injury result in BO, suggesting that epithelial damage per se is not the critical event leading to the development of BO...
November 2013: American Journal of Respiratory Cell and Molecular Biology
Xia Gao, Christopher M Vockley, Florencia Pauli, Kimberly M Newberry, Yan Xue, Scott H Randell, Timothy E Reddy, Brigid L M Hogan
Most of the airways of the human lung are lined by an epithelium made up of ciliated and secretory luminal cells and undifferentiated basal progenitor cells. The integrity of this epithelium and its ability to act as a selective barrier are critical for normal lung function. In other epithelia, there is evidence that transcription factors of the evolutionarily conserved grainyheadlike (GRHL) family play key roles in coordinating multiple cellular processes required for epithelial morphogenesis, differentiation, remodeling, and repair...
June 4, 2013: Proceedings of the National Academy of Sciences of the United States of America
Fen Huang, Hongkang Zhang, Meng Wu, Huanghe Yang, Makoto Kudo, Christian J Peters, Prescott G Woodruff, Owen D Solberg, Matthew L Donne, Xiaozhu Huang, Dean Sheppard, John V Fahy, Paul J Wolters, Brigid L M Hogan, Walter E Finkbeiner, Min Li, Yuh-Nung Jan, Lily Yeh Jan, Jason R Rock
Mucous cell hyperplasia and airway smooth muscle (ASM) hyperresponsiveness are hallmark features of inflammatory airway diseases, including asthma. Here, we show that the recently identified calcium-activated chloride channel (CaCC) TMEM16A is expressed in the adult airway surface epithelium and ASM. The epithelial expression is increased in asthmatics, particularly in secretory cells. Based on this and the proposed functions of CaCC, we hypothesized that TMEM16A inhibitors would negatively regulate both epithelial mucin secretion and ASM contraction...
October 2, 2012: Proceedings of the National Academy of Sciences of the United States of America
Xia Xu, Jason R Rock, Yun Lu, Christopher Futtner, Brian Schwab, Justin Guinney, Brigid L M Hogan, Mark W Onaitis
Identifying the cells of origin of lung cancer may lead to new therapeutic strategies. Previous work has focused upon the putative bronchoalveolar stem cell at the bronchioalveolar duct junction as a cancer cell of origin when a codon 12 K-Ras mutant is induced via adenoviral Cre inhalation. In the present study, we use two "knock-in" Cre-estrogen receptor alleles to inducibly express K-RasG12D in CC10(+) epithelial cells and Sftpc(+) type II alveolar cells of the adult mouse lung. Analysis of these mice identifies type II cells, Clara cells in the terminal bronchioles, and putative bronchoalveolar stem cells as cells of origin for K-Ras-induced lung hyperplasia...
March 27, 2012: Proceedings of the National Academy of Sciences of the United States of America
Jason R Rock, Christina E Barkauskas, Michael J Cronce, Yan Xue, Jeffrey R Harris, Jiurong Liang, Paul W Noble, Brigid L M Hogan
There are currently few treatment options for pulmonary fibrosis. Innovations may come from a better understanding of the cellular origin of the characteristic fibrotic lesions. We have analyzed normal and fibrotic mouse and human lungs by confocal microscopy to define stromal cell populations with respect to several commonly used markers. In both species, we observed unexpected heterogeneity of stromal cells. These include numerous cells with molecular and morphological characteristics of pericytes, implicated as a source of myofibroblasts in other fibrotic tissues...
December 27, 2011: Proceedings of the National Academy of Sciences of the United States of America
Zea Borok, Jeffrey A Whitsett, Peter B Bitterman, Victor J Thannickal, Darrell N Kotton, Susan D Reynolds, Mark A Krasnow, Diana W Bianchi, Edward E Morrisey, Brigid L Hogan, Jonathan M Kurie, David C Walker, Derek C Radisky, Steve L Nishimura, Shelia M Violette, Paul W Noble, Steve D Shapiro, Carol J Blaisdell, Harold A Chapman, James Kiley, Dorothy Gail, Deborah Hoshizaki
In April 2010, a NIH workshop was convened to discuss the current state of understanding of lung cell plasticity, including the responses of epithelial cells to injury, with the objectives of summarizing what is known, what the field needs to know, and how to get there. The proximal stimulus for this workshop is the body of recent evidence suggesting that plasticity is a prominent but incompletely characterized property of lung epithelial cells, and that a focus on understanding this aspect of epithelial cell biology in particular, may be an important window into disease pathobiology and pathogenesis...
June 2011: Proceedings of the American Thoracic Society
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