2024 CALA seminar
Ke Yuan
From: SCBA Society <ad...@scbasociety.org>
Date: Sun, Sep 8, 2024 at 9:57 AM
Subject: Announcement: AASF Hosts Public Forum with NIH Director & Principal Deputy Director (9/19 at 3pm ET)
To: Anny Xiaobo Zhou <xiaob...@channing.harvard.edu>
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Ke Yuan
CALA Happy Friday Seminar
September 13, 2024
Time: EST 9:00 pm; PST: 6:00 pm; Beijing time: September 14, 9:00 am
Zoom: 849 9682 9273 (Password: 654321)
Macrophage Heterogeneity and Function in the Lung
Graduate Student
Dartmouth Geisel School of Medicine
Bio: Xin Li was born in China and graduated from Peking University in 2016. He earned his master's degree from University of Southern California and is currently pursuing his PhD in Dr. Claudia Jakubzick's lab at Dartmouth College. Xin's primary research focus is examining myeloid cell heterogeneity and functionality using both in silico and in vivo approaches. He is particularly interested in the division of labor within the myeloid population during various homeostasis and various immune responses, as well as the interacting networks among different cells.
Abstract: Lung-resident macrophages, which include alveolar macrophages (AMs) and interstitial macrophages (IMs), exhibit a high degree of diversity, generally attributed to different activation states, and often complicated by the influx of monocytes into the pool of tissue-resident macrophages. To gain a deeper insight into the functional diversity of IMs, we perform comprehensive transcriptional profiling of resident IMs and reveal ten distinct chemokine-expressing IM subsets at steady state and during inflammation. Similar IM subsets that exhibited coordinated chemokine signatures and differentially expressed genes were observed across various tissues and species, indicating conserved specialized functional roles. Depletion of CD206hi IMs in Pf4creR26EYFP+DTR and Pf4creR26EYFPCx3cr1DTR mice led to diminished inflammatory cell recruitment, reduced tertiary lymphoid structure formation and fewer germinal center B cells in models of allergen- and infection-driven inflammation in the mouse lung. These observations highlight the specialized roles of IMs, defined by their coordinated chemokine production, in regulating immune cell influx and organizing tertiary lymphoid tissue architecture. On the other hand, the heterogeneity of human AMs has been revealed using single-cell RNA sequencing (scRNA-seq) in healthy humans, identifying subsets with distinct functional gene patterns, such as metal ion binding (MT.AMs), interferon response (IFN.AMs), growth factor secretion, cholesterol and lipid biosynthesis, antigen presentation, and unique chemokine expressions. In contrast, AMs from naïve pathogen-free mice are traditionally viewed as homogeneous. However, we demonstrate that mouse AMs exhibit diverse transcriptional profiles similar to their human counterparts. Gene expression profiling revealed several analogous AM subsets in mice, such as IFN.AMs and MT.AMs, alongside with some unique subsets without clear human counterparts. Overall, our study provides new insights into the lung resident macrophage population, emphasizing their heterogeneity and potential functions in both mouse and human.
Ke Yuan
Ke Yuan
CHINESE-AMERICAN LUNG ASSOCIATION
CALA Happy Friday Seminar
September 27, 2024
Time: EST 9:00 pm; PST: 6:00 pm; Beijing time: September 28, 9:00 am
Zoom: 849 9682 9273 (Password: 654321)
TSC2 deficiency promotes Pulmonary Vascular Smooth Muscle Cell Proliferation in Pulmonary Hypertension
Yuanjun Shen, PhD
Current position: Postdoctoral Scholar, University of Delaware
Offer accepted: Assistant Professor, School of Pharmacy and Pharmaceutical Sciences, Binghamton University
Bio: Dr. Yuanjun Shen earned his Ph.D. in Pharmaceutical Science from the University of Rhode Island in 2017. He then began his postdoctoral training in pulmonary hypertension research under Dr. Elena Goncharova, first at the University of Pittsburgh and later at the University of California, Davis. In 2023, Dr. Shen received the prestigious NIH K99/R00 grant to support his research on pulmonary hypertension. That same year, he joined Dr. Jason Gleghorn’s biomedical engineering lab to gain expertise in microfluidic device design and its applications in pulmonary research. Starting January 1, 2025, Dr. Shen will join the School of Pharmacy and Pharmaceutical Sciences at Binghamton University as an Assistant Professor, where he will continue his research.
Abstract: Increased proliferation and survival of cells in small pulmonary arteries (PAs) drive pulmonary arterial hypertension (PAH). Because cell growth mediated by the mTOR-containing mTORC1 complex is inhibited by tuberous sclerosis complex 2 (TSC2), we investigated the role of this GTPase-activating protein in PAH pathology. TSC2 abundance was decreased in remodeled small PAs and PA vascular smooth muscle cells (PAVSMCs) from patients with PAH or from rodent pulmonary hypertension (PH) models, as well as PAVSMCs maintained on substrates that reproduced pathology-induced stiffness. Accordingly, mice with smooth muscle–specific reduction in TSC2 developed PH. At the molecular level, decreased TSC2 abundance led to stiffness-induced PAVSMC proliferation, increased abundance of the mechanosensitive transcriptional coactivators YAP/TAZ, and enhanced mTOR kinase activity. Moreover, extracellular matrix (ECM) produced by TSC2-deficient PAVSMCs stimulated the proliferation of non-diseased PA adventitial fibroblasts and PAVSMCs through fibronectin and its receptor, the α5β1 integrin. Reconstituting TSC2 in PAVSMCs from patients with PAH through overexpression or treatment with the SIRT1 activator SRT2104 decreased YAP/TAZ abundance, mTOR activity, and ECM production, as well as inhibited proliferation and induced apoptosis. In two rodent models of PH, SRT2104 treatment restored TSC2 abundance, attenuated pulmonary vascular remodeling, and ameliorated PH. Thus, TSC2 in PAVSMCs integrates ECM composition and stiffness with pro-proliferative and survival signaling, and restoring TSC2 abundance could be an attractive therapeutic option to treat PH.
Ke Yuan
Ke Yuan
Ke Yuan
CALA Happy Friday Seminar
October 11th, 2024
Time: EST 9:00 pm; PST: 6:00 pm; Beijing time: October 11th, 9:00 am
Zoom: 849 9682 9273 (Password: 654321)
Pulmonary Ionocyte Regulate Chloride Secretion and Absorption via CFTR
Feng Yuan, Ph.D.
Current position: Assistant Research Scientist, The University of Iowa
Offer accepted: Assistant Professor, Gregory Fleming James Cystic Fibrosis Research Center; Department of Medicine; Division of Pulmonary, Allergy, and Critical Care Medicine; The University of Alabama at Birmingham
Bio: Dr. Feng Yuan earned his PhD from Zhongshan School of Medicine at Sun Yat-sen University. While at Sun Yat-sen University, he worked with Dr. Guanlei Wang, focusing on ion channel properties and their roles in biological and diseased processes. In 2017, he began his postdoctoral training in the field of cystic fibrosis lung disease in Dr. John Engelhardt’s lab. As a postdoctoral researcher at the University of Iowa, he focused on airway stem cell biology, ion channel biophysics, gene editing, and large animal models, such as ferrets, to study cystic fibrosis genetic diseases. He participated in discovering pulmonary ionocyte (Montoro D et al. Nature, 2018, 560: 319-324), demonstrating the conserved FOXI1 signaling pathway regulates pulmonary ionocyte specification in mammals. To delineate pulmonary ionocyte function and biology, he created multiple transgenic ferret models to track, tweak, and delete ionocyte function. He demonstrated that ionocytes mediate both air surface liquid absorption and secretion via CFTR-dependent transport of chloride and bicarbonate (Yuan F et al. Nature, 2023, 621:857-867). In 2024, Dr. Yuan was honored with the Cystic Fibrosis Research Institution New Horizon Award and the Cystic Fibrosis Foundation Spring Research Grant. Starting in December 2024, Dr. Yuan will join the Department of Medicine, Pulmonary Division at The University of Alabama at Birmingham as an assistant professor on the tenure track. He will establish Yuan Lab and conduct his research. His laboratory is currently accepting postdoctoral researchers and graduate students. Contact Email: fyu...@uab.edu
Abstract: Conflicting evidence has emerged regarding the role of pulmonary ionocytes in regulating air surface liquid volume. Pulmonary ionocytes have been shown to mediate fluid absorption by different groups, but whether ionocytes and/or secretory cells mediate anion secretion remains unclear. An improved understanding of cell-type-specific contributions to anion secretion will provide the foundation for enhancing the efficacy of therapeutic approaches.
FOXI1-KO ferrets were used for ionocyte depletion studies. FOXI1-CreERT2::CFTRL/L ferrets induced with tamoxifen were used for ionocyte-specific CFTR deletion studies. We are generating ionocyte-specific CFTR reactivation ferrets: FOXI1-CreERT2::CFTRcKI. Those CF ferrets induced with tamoxifen will be used for ionocyte-specific CFTR reactivation studies.
Ke Yuan
CALA Happy Friday Seminar
October 11th, 2024
Time: EST 9:00 pm; PST: 6:00 pm; Beijing time: October 12th, 9:00 am
Zoom: 849 9682 9273 (Password: 654321)
Pulmonary Ionocyte Regulate Chloride Secretion and Absorption via CFTR
Feng Yuan, Ph.D.
Current position: Assistant Research Scientist, The University of Iowa
Offer accepted: Assistant Professor, Gregory Fleming James Cystic Fibrosis Research Center; Department of Medicine; Division of Pulmonary, Allergy, and Critical Care Medicine; The University of Alabama at Birmingham
Ke Yuan
Ke Yuan
CALA Happy Friday Seminar
October 25th, 2024
Time: EST 9:00 pm; PST: 6:00 pm; Beijing time: October 26th, 9:00 am
Zoom: 849 9682 9273 (Password: 654321)
Proton channel regulates PH (Pulmonary Hypertension)
Liang Hong, Ph.D.
Assistant Professor
University of Illinois Chicago
Bio: Liang obtained a bachelor’s degree in clinical medicine from the Anhui Medical University and did a Ph.D. in the Department of Pharmacology at Sun Yat-Sen University. After Liang graduated, he moved to the University of California Irvine (UCI) for postdoc training and joined Dr. Tombola’s lab to study proton channel pharmacology. Liang was then appointed Research AP, working in Dr. Darbar’s lab at the University of Illinois Chicago (UIC), and studying cardiac sodium channels. Liang was appointed tenure-track assistant professor and started his lab in May 2021. Liang is an ion channel researcher, and his research is focused on ion channel-related cardiovascular disease.
Abstract: Pulmonary hypertension (PH) is a major public health challenge in the US and worldwide. It places a huge burden on healthcare costs in society, with frequent hospitalizations and the associated morbidity and increased mortality. PH has a complex pathophysiology that involves oxidative stress-induced pulmonary vascular remodeling. Despite tremendous research efforts that have been made in pulmonary responses to oxidative stress, the molecular basis driving oxidative stress in PH is poorly understood. The voltage-gated proton channel Hv1 is the last member discovered in the family of the voltage-gated ion channel. Hv1 plays a crucial role in pH homeostasis and promotes the production of reactive oxygen species (ROS) to enhance oxidative stress. Here, we found that the Hv1 proton channel is implicated in the pathogenesis of PH; we studied the role of Hv1 in the progression of this disease.
Ke Yuan
Xiaobo Zhou
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Xiaobo Zhou, Ph.D.
Director of Functional Genomics Laboratory
Brigham and Women's Hospital, Harvard Medical School
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Ke Yuan
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Xiaobo Zhou, Ph.D.Associate Professor, Harvard Medical SchoolPhone: 617-525-7866
Director of Functional Genomics Laboratory
Brigham and Women's Hospital, Harvard Medical School
The information in this email is intended only for the person to whom it is addressed. If you believe this e-mail was sent to you in error and the email contains patient information, please contact the Partners Compliance HelpLine at http://www.partners.org/complianceline . If the email was sent to you in error but does not contain patient information, please contact the sender and properly dispose of the email.
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Ke Yuan
CALA Happy Friday Seminar
December 20th, 2024
Time: EST 9:00 pm; PST: 6:00 pm; Beijing time: December 21st, 10:00 am
Zoom: 849 9682 9273 (Password: 654321)
Cell competition drives bronchiolization and pulmonary fibrosis
Stijn P. De Langhe, PhD,
Professor
Division of Pulmonary and Critical Care Medicine,
Department of Internal Medicine,
Mayo Clinics
Bio: Dr. Stijn De Langhe is a Professor in the Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine at Mayo Clinics in Rochester. He received his PhD from Belgium at Ghent University and pursued his postdoc at Childrens Hospital Los Angeles at USC Keck School of Medicine. The goal of Dr. De Langhe's research is to define the molecular mechanisms underlying lung development and to determine how these mechanisms can be harnessed to improve repair and regeneration in the lung. His team seeks to clarify the mechanistic basis of bidirectional signaling between lung stem cells and their niche, which informs lung stem cell fate decisions, including choices between quiescence or proliferation, self-renewal or differentiation, migration or retention, and cell death or survival.
Abstract: Epithelial stem/progenitor cells and their mesenchymal niches are crucial for tissue repair, with regeneration outcomes depending on injury type and severity. Cell competition influences whether repair leads to lung regeneration or fibrosis. In tissues with imbalanced cMyc or Yap levels, "super-competitor" cells with higher levels outcompete and eliminate others. Following injury, surviving stem cells may gain a competitive advantage, even if less effective at repair. For example, SARS-CoV-2 infects respiratory cells via ACE2, with varying ACE2 expression making some stem cells more susceptible. Modulating cell competition mechanisms may provide a strategy for treating lung injuries and diseases like IPF and ARDS.
