2023 CALA Friday Seminars
Ke Yuan
CALA Happy Friday Seminar
April 7th, 2023
Time: EST 9:00 pm; PST: 6:00 pm; Beijing time: 3/18, 9:00 am
Zoom: 849 9682 9273 (Password: 654321)
An overview of the antiviral drug discovery process targeting respiratory viruses
Jun Wang, Ph.D.
Associate Professor
Rutgers, The State University of New Jersey
Bio: Jun Wang received his bachelor's degree in chemistry from Wuhan University, China in 2003. He subsequently worked for one year as a research scientist in Scinopharm Biomedical Co. Ltd in Kunshan, Jiangsu province. In 2004, he joined the Department of Chemistry at the National University of Singapore studying the matrix metalloprotease using activity-based chemical probes and peptidomimetic inhibitors under the supervision of Dr. Shaoqin Yao. He received the MS degree in 2006 and moved to the Department of Chemistry at the University of Pennsylvania. He joined Dr. William F. DeGrado’s group and worked on the design of channel blockers targeting the drug-resistant influenza A virus M2 proton channel. After graduating in 2010 with a PhD degree in organic chemistry, he continued the postdoctoral research in the DeGrado lab and relocated with the lab to UCSF in 2011. Dr. Wang started his independent academic career in 2014 as an Assistant Professor at the Department of Pharmacology and Toxicology at the University of Arizona. In 2020, he was promoted to Associate Professor with Tenure. Dr. Wang received the ABRC Young Investigator Award in 2017 and the College of Pharmacy A. Jay Gandolfi New Investigator Award in 2019. In 2022, he moved his lab to the Department of Medicinal Chemistry, Ernest Mario School of Pharmacy, Rutgers University. Dr. Wang is the editorial board member of multiple journals. He is also a frequent ad hoc reviewer for multiple NIH study sections. His current research interests are the medicinal chemistry and pharmacology of antivirals targeting emerging and re-emerging viruses including influenza virus, enterovirus, and coronavirus. Dr. Wang’s research has been funded by grants from National Institutes of Health, ABRC, and PhRMA foundation.
Abstract: My lab focuses on developing antivirals targeting emerging and re-emerging viruses, including influenza A and B viruses, enterovirus D68 (EV-D68), EV-A71, coxsackievirus, poliovirus, and the coronaviruses such as SARS-CoV-2. The central theme of the Wang laboratory has been the identification of new drug targets and the development of novel small molecules for use as chemical probes for target validation as well as drug candidates for translational research. In this presentation, I will give a brief overview of the antiviral drug discovery processes targeting respiratory viruses and use our own research on SARS-CoV-2 main protease as an example.
Ke Yuan
Ke Yuan
CALA Happy Friday Seminar
April 7th, 2023
Time: EST 9:00 pm; PST: 6:00 pm; Beijing time: 3/18, 9:00 am
Zoom: 849 9682 9273 (Password: 654321)
An overview of the antiviral drug discovery process targeting respiratory viruses
Jun Wang, Ph.D.
Associate Professor
Rutgers, The State University of New Jersey
Ke Yuan
CALA Happy Friday Seminar
April 14th, 2023
Time: EST 9:00 pm; PST: 6:00 pm; Beijing time: 3/18, 9:00 am
Zoom: 849 9682 9273 (Password: 654321)
Lung Dopaminergic Nerves Facilitate the Development of Allergic Asthma
Xingbin Ai, Ph.D.
Associate Professor of Pediatrics
MGH, Harvard Medical School
Abstract: Allergic asthma develops from allergen exposure in early childhood and progresses into adulthood. The central mediator of progressive allergic asthma is allergen-specific, T helper 2 (Th2) resident memory cells (TRMs). However, whether the immature lung fosters the residence of Th2-TRMs is unknown. Employing a mouse model of progressive allergic inflammation from neonates to adults, we have found that maturing sympathetic nerves enable a dopamine-enriched lung environment in early life to promote the establishment of allergen-specific Th2-TRMs. We showed that sympathetic nerves initiate a dopaminergic-to-adrenergic maturation process overlapping the contraction phase following neonatal allergen exposure. These predominantly dopaminergic nerves signal to neighboring effector Th2 cells through a dopamine-DRD4 pathway to activate the residence program. Blockade of dopamine-DRD4 signaling following neonatal allergen exposure impaired lung residence of Th2 cells and ameliorated anamnestic allergic inflammation in adults. Taken together, the immature lung imparts age-related, sympathetic nerve-derived dopamine to facilitate asthma progression into adulthood.
Bio: Dr. Ai majors in Genetics as an undergraduate at Fudan University and Neurosciences as a Ph.D. student at Case Western Reserve University. Dr. Ai’s postdoc training at the University of Pennsylvania is in the field of Cell & Developmental Biology. Dr. Ai joined the Pulmonary Center, Boston University School of Medicine, as an Assistant Professor of Medicine in 2008 and is an Associate Professor of Pediatrics at Mass General Hospital, Harvard Medical School. Dr. Ai leads a NIH-funded research program that investigates nerve-derived mechanisms underlying the susceptibility to allergic asthma in children. Dr. Ai has recently evolved new projects that utilize tracheal aspirate-derived airway basal stem cells as a translational model to investigate lung defects in newborns suffering from a variety of respiratory conditions. Dr. Ai serves as a member of NHLBI training grant review panel and a departmental representative on MGH Research Council.
Ke Yuan
Ke Yuan
CALA Happy Friday Seminar
April 28th , 2023
Time: EST 9:00 pm; PST: 6:00 pm; Beijing time: 4/29, 9:00 am
Zoom: 849 9682 9273 (Password: 654321)
Lymphangioleiomyomatosis (LAM):
Answered and Unanswered Questions
Kai-Feng Xu, M.D. Ph.D.
Professor
Department of PCCM, PUMC Hospital, Beijing, China
Bio: Dr. Kai-Feng Xu graduated from Shanghai Medical University in 1988 and joined Peking Union Medical College (PUMC) hospital as a resident in the Department of Internal Medicine. He got his master’s degree from the University of Melbourne, Australia in 1997, and his doctorate degree from PUMC in 2002. He was a research fellow at NHLBI, NIH between 2002 and 2005. Dr. Xu’s major research interests include rare lung diseases, including lymphangioleiomyomatosis (LAM), pulmonary alveolar proteinosis (PAP), cystic fibrosis (CF), etc. He is a leading pulmonary physician in rare lung diseases in China. He is also interested in air pollution studies on asthma and chronic obstructive pulmonary disease (COPD).
Abstract: Lymphangioleiomyomatosis (LAM) is a rare cystic lung disease in women. It can be sporadic or associated with a genetic disease tuberous sclerosis complex (TSC). LAM is a low-grade metastatic neoplastic disease; however, the origin of LAM cells is a mystery yet. Lymphatic circulation is frequently involved and destructed. Because of the overactivation of mTOR resulting from TSC2 mutations, sirolimus (rapamycin) treated patients successfully in maintaining lung function, reducing tumor sizes and improving survival. His most recent finding was published in Chest.
Ke Yuan
| 1. CALA Happy Friday Seminar |
April 28th , 2023 Time: EST 9:00 pm; PST: 6:00 pm; Beijing time: 4/29, 9:00 am Zoom: 849 9682 9273 (Password: 654321) Lymphangioleiomyomatosis (LAM): Answered and Unanswered Questions Kai-Feng Xu, M.D. Ph.D. Professor Department of PCCM, PUMC Hospital, Beijing, China Bio: Dr. Kai-Feng Xu graduated from Shanghai Medical University in 1988 and joined Peking Union Medical College (PUMC) hospital as a resident in the Department of Internal Medicine. He got his master’s degree from the University of Melbourne, Australia in 1997, and his doctorate degree from PUMC in 2002. He was a research fellow at NHLBI, NIH between 2002 and 2005. Dr. Xu’s major research interests include rare lung diseases, including lymphangioleiomyomatosis (LAM), pulmonary alveolar proteinosis (PAP), cystic fibrosis (CF), etc. He is a leading pulmonary physician in rare lung diseases in China. He is also interested in air pollution studies on asthma and chronic obstructive pulmonary disease (COPD). Abstract: Lymphangioleiomyomatosis (LAM) is a rare cystic lung disease in women. It can be sporadic or associated with a genetic disease tuberous sclerosis complex (TSC). LAM is a low-grade metastatic neoplastic disease; however, the origin of LAM cells is a mystery yet. Lymphatic circulation is frequently involved and destructed. Because of the overactivation of mTOR resulting from TSC2 mutations, sirolimus (rapamycin) treated patients successfully in maintaining lung function, reducing tumor sizes and improving survival. His most recent finding was published in Chest. |
| 2. Dear Members of the CALA, We are pleased to share that two of our members, Drs Yuanjun Shen and Yan Hu, have been awarded a K99 grant from NIH. This is a tremendous achievement. We are proud to have members like Yuanjun and Yan, who are committed to improving lung health and reducing lung disease burden.This grant is a recognition of their hard work, dedication, and outstanding research capabilities. Let us take a moment to congratulate Yuanjun and Yan on this remarkable achievement.As they move forward in their careers, we hope to support them in every way possible. One of the next steps for Yuanjun and Yan is to secure a faculty position, and we believe that the expertise and dedication they have shown in their work would make them excellent candidates for such a position.We kindly request the favor of our members to help Yuanjun and Yan by sharing information about any available faculty positions that may be suitable for their research interests and expertise. Any leads or referrals you can provide would be greatly appreciated and could make a significant difference in their careers. CALA Committee |
Ke Yuan
Ke Yuan
CALA Happy Friday Seminar
May 6th , 2023
Time: EST 9:00 pm; PST: 6:00 pm; Beijing time: May 7th, 9:00 am
Zoom: 849 9682 9273 (Password: 654321)
Human Organ Chips for Disease Modeling and Drug Discovery
Haiqing Bai, Ph.D.
Director, Preclinical Development
Xellar Inc., Newton, MA
Bio: Haiqing Bai is the Director of Preclinical Development at Xellar Inc., a startup company headquartered in Boston, MA that specializes in utilizing human organ chip disease models, high-content imaging, and machine learning for drug discovery. Dr. Bai received his B.S. from the University of Science and Technology of China in 2012 and went on to complete his Ph.D. in Pathology from the University of Rochester in 2018. He then had his postdoctoral training under the mentorship of Dr. Donald Ingber at the Wyss Institute at Harvard University between 2018 and 2022 where he served as a Wyss Technology Development Fellow. Dr. Bai’s research centers on disease modeling and drug discovery using complex in-vitro models, such as human organ chips. His research interest in lung diseases includes respiratory infection, acute respiratory distress syndrome (ARDS), and lung fibrosis. His work in these areas has been published in journals including Nature Biomedical Engineering and Nature Communications and has led to multiple patent applications.
Abstract: The intertwined relationship between structure and function has been key to understanding human organ physiology and disease pathogenesis. An organ-on-a-chip (organ chip) is a bioengineered microfluidic cell culture device lined by living cells and tissues that aims to recapitulate in-vivo organ structure and function. In this talk, I will provide an overview of the organ chip field and use the lung chip as an example to demonstrate how this emerging technology has transformed our approach to studying human disease mechanisms, assessing drug toxicity and efficacy, and ultimately developing new therapies.
Ke Yuan
CALA Happy Friday Seminar
May 5th , 2023
Time: EST 9:00 pm; PST: 6:00 pm; Beijing time: May 6th, 9:00 am
Zoom: 849 9682 9273 (Password: 654321)
Human Organ Chips for Disease Modeling and Drug Discovery
Haiqing Bai, Ph.D.
Director, Preclinical Development
Xellar Inc., Newton, MA
Ke Yuan
Ke Yuan
Time: Sat, May 20th 2023 5-8pm
Address: Chinatown Garden, 龙之味， 618 H St NW, Washington, DC 20001
5pm-6pm: Arrival and Registration
6pm Dinner start
6:30pm: Welcome and introduction by Ke Yuan ( Boston Children’s Hospital)
6:30-7:15pm: Award ceremony and talks
Moderator: Yan Hu (University of Colorado)
Service Award: Zhiyu Dai ( University of Arizona)
Trainee Award: Yinshan Fang ( Columbia University) and Xue Liu (Cedars-Sinai Medical Center)
Established investigator award: Jie Sun ( University of Virginia)
7:20-7:50pm: Panel discussion “Leadership and career development”
Moderator: Xiaobo Zhou ( Brigham and Women's Hospital)
Panelists:
Paul Yu ( Director, Cardiovascular Research Center, Massachusetts General Hospital)
Paul Liu (Deputy Scientific Director of NHGRI)
7:50-8:30pm: Network and Adjourns
Dinner Sponsor: Vazyme
Ke Yuan
CALA Happy Friday Seminar
June 2nd, 2023
Time: EST 9:00 pm; PST: 6:00 pm; Beijing time: June 3rd, 9:00 am
Zoom: 849 9682 9273 (Password: 654321)
Unraveling the Mechanisms of Impaired Tissue Regeneration by Club Cells in COPD
Yan Hu, Ph.D.
Postdoc Fellow
University of Colorado
Bio: Dr. Yan Hu received her B.S. degree from China Agricultural University in 2009 and obtained her Ph.D. training at the University of Virginia from 2010 to 2016. In 2017, she joined Dr. Melanie Königshoff’s laboratory at the University of Colorado Division of Pulmonary Science and Critical Care as a postdoctoral fellow, studying distal lung epithelial progenitor functions in chronic obstructive pulmonary disease (COPD). She has received an NRSA F32 grant from NHLBI in 2018. In 2020, Dr. Hu switched to Dr. Christopher Evans’ group at CU, when Dr. Koenigshoff moved to the University of Pittsburgh. Since then, she has developed her own research program on dissecting the functional heterogeneity of airway club cells in health and COPD. Dr. Hu recently received a K99 award from NHLBI to expand her future independent research on the mechanisms regulating progenitor functions of airway club cells in lung diseases.
Abstract: Emphysema, the progressive and irreversible destruction of the fibroelastic scaffold of alveolar tissue, is a hallmark of chronic obstructive pulmonary disease (COPD). The cause of failed regeneration in emphysema is unknown and no effective curative therapy is clinically available. Small airway club cells were shown to repair alveolar tissue after acute injuries. However, their function in emphysema remains largely unknown. Through combined single cell RNA-seq in patient and mouse tissues and lineage tracing of club cells in the elastase mouse model of emphysema with in situ analysis, as well as functional organoid formation assays, we discovered an emphysema associated state of ATII cells, which was characterized by airway club cell origin and poor capacity of alveolar regeneration. Further, we have discovered overexpression of a gel-forming mucin, Muc5b, in terminal bronchiolar club cells in a mouse emphysema model, which do not produce mucin in health. Further analysis using transgenic mice over-expressing Muc5b and mice with conditional knockout of Muc5b, we showed that Muc5b overproduction in the terminal airway impaired the alveolar regeneration capacity of club cells, and that removing Muc5b improved tissue regeneration in emphysema. Therefore, our studies suggest that alveolar repair by airway club cells in COPD may serve as an emergency route, however with limited regenerative potential. Further, the functional shift of club cells from alveolar repair to mucin secretion in emphysema connects the pathogenesis of small airway disease and emphysema.
Ke Yuan
Ke Yuan
Ke Yuan
Ke Yuan
CALA Happy Friday Seminar
June 23rd, 2023
Time: EST 9:00 pm; PST: 6:00 pm; Beijing time: June 24th, 9:00 am
Zoom: 849 9682 9273 (Password: 654321)
Transgenic Ferret Models Define Pulmonary Ionocyte Origins and Function
Feng Yuan, Ph.D.
Assistant Research Scientist
Anatomy and Cell Biology, University of Iowa
Bio: Dr. Feng Yuan is an Assistant Research Scientist, at Anatomy and Cell Biology Department, University of Iowa. Dr. Feng Yuan obtained his PhD at Zhongshan School of Medicine, Sun Yat-sen University. His work at Sun Yat-sen University focused on ion channel properties and understanding their roles in biological and diseased processes. In 2017, Dr. Feng Yuan joined Dr. John Engelhardt’s lab for his postdoctoral training in the field of airway stem cells. As a postdoctoral researcher at University of Iowa, Feng Yuan works on airway stem cell biology, gene editing, large animal models like ferrets and cystic fibrosis genetic diseases. In 2018, Dr. Feng Yuan participated in the discovery of CFTR enriched ionocyte, a previously unknow cell type which was similar to fish gill and frog skin cells. This previous work raised a major controversy regarding the potential role of these “rare cells” including their primary role in Cystic Fibrosis pathogenesis. The current study takes on controversy by developing the tools to define the development and identity of ionocytes more accurately.
Abstract: Pulmonary ionocytes (PIs) are distinguished by high expression of the transcription factor FOXI1, V-ATPases, and other ion channels such as CFTR. Consistent with this expression pattern, ionocytes in fish and frogs have confirmed roles in regulating salt and fluid movement; however, in vivo functions of ionocytes in mammalian respiratory systems remains unclear. Here we describe the creation and use of novel conditional genetic ferret models to dissect pulmonary ionocyte biology and function by enabling ionocyte lineage tracing (FOXI1-CreERT2::ROSA-TG), ionocyte ablation (FOXI1-KO), and ionocyte-specific deletion of CFTR (FOXI1-CreERT2::CFTRL/L).
Ke Yuan
Ke Yuan
Understand what it is.
Should you apply?
Plan your timeline.
Get advice from current awardees.
EST 9:00pm; PST 6:00pm
Zoom: 849 9682 9273
Password: 654321
Xue Liu PhD, Cedars-Sinai Medical Center
Ke Yuan
Ke Yuan
Ke Yuan
CALA Happy Friday Seminar
Sept 8th, 2023
Time: EST 9:00 pm; PST: 6:00 pm; Beijing time: 3/18, 9:00 am
Zoom: 849 9682 9273 (Password: 654321)
Ying Xi, Ph.D.
Assistant Professor
Shanghai Tech University
Title: WISP1-MRTF signaling promotes myofibroblast motility and fibrosis progression
Bio: Dr. Xi received her B.S. in Biology from Nanjing University and her Ph.D. in Biochemistry and Molecular Biology from Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences. She did her postdoc training in Dr. Hal Chapman lab at University of California, San Francisco in 2010-2016. In 2016, she joined the Discovery Immunology Department at Genentech Inc. Dr. Xi started her independent academic career in 2019 as an Assistant Professor at School of Life Science and Technology at ShanghaiTech University. Her research interests are lung regeneration and fibrosis.
Abstract: Progressive fibrotic disease characterized by aberrant fibroblast/ myofibroblast accumulation and excessive collagen matrix deposition can lead to organ malfunction and, ultimately death, as exemplified in idiopathic pulmonary fibrosis (IPF) and liver cirrhosis. Although numerous efforts have been made to identify mediators of the acute fibrotic response, the molecular underpinnings of chronic fibrosis progression in human patients remain poorly understood. Here, we identify a pathway involving WNT inducible signaling pathway protein 1 (WISP1) and myocardin related transcription factor (MRTF) as a central mechanism driving fibrosis progression through transcriptional reprogramming of fibroblast/myofibroblast cytoskeleton and motility. WISP1 expression is highly correlated with MRTF activity in human IPF lungs and cirrhotic livers and can activate MRTF signaling via multiple integrins including αVβ1/3/5/8 and α11β1 in vitro. In mice, WISP1 deficiency protects against fibrosis progression but not fibrosis onset and leads to reduced myofibroblast accumulation in tissue interstitial areas and diminished expression of MRTF target cytoskeleton genes. Therapeutic administration of a novel antibody blocking WISP1-MRTF signaling axis halted the progression of existing liver fibrosis. More interestingly, the first approved IPF medication, pirfenidone (PFD) inhibits MRTF activation in primary human lung fibroblasts at clinically achievable concentrations. Our results thus reveal myofibroblast cytoskeleton and motility reprogramming as a critical cellular event directing fibrosis progression and establish the WISP1-MRTF pathway as a target for clinical intervention in progressive fibrotic disease.
Ke Yuan
Ke Yuan
CALA Happy Friday Seminar
Sep 15th, 2023
Time: EST 9:00 pm; PST: 6:00 pm; Beijing time: Sept 16th, 9:00 am
Zoom: 849 9682 9273 (Password: 654321)
Nathan Salomonis, Ph.D.
Associate Professor in Biomedical Informatics
Cincinnati Children’s Hospital
Dr. Nathan Salomonis co-directs the NHBLI LungMAP II Data Coordination Center and Pediatric Cell Atlas initiatives at Cincinnati Children’s Hospital and participates in CZI funded Human Cell Atlas bioinformatics efforts.
Research Focus: The role of alternative splicing in both human development and disease is profound. Unique alternative isoforms govern opposing transcriptional, signaling and cell survival responses that can drive differentiation to new lineages or blunt responses to chemotherapies. My research aims to reveal hidden splicing single-cell networks that underlie normal cell differentiation and disease. To aid in this work, my lab has developed numerous computational approaches to resolve single-cell populations and define core regulatory networks that derive from altered transcriptional or splicing programs. These tools have provided the engine for us to discover key molecular regulators of stem cell fate decisions in embryonic stem cells (splicing, microRNA targeting) and bone marrow failure syndromes (Ski induced splicing dysregulation), define new cellular hierarchies in normal hematopoiesis (metastable cell states), and mechanistic determinants of inherited and malignant disease (re-wiring of RNA binding protein interactions). Our current work applies deep learning to design new cancer vaccines, identify novel isoforms that alter tumor extracellular signaling and game theory to resolve clonal heterogeneity in cancer.
Ke Yuan
Ke Yuan
CALA Happy Friday Seminar
Sep 22nd, 2023
Time: EST 9:00 pm; PST: 6:00 pm; Beijing time: Sep 23rd, 9:00 am
Engineered lung tissue models for modeling disease progression and anti-fibrosis treatment in pulmonary fibrosis
Ruogang Zhao Ph.D.
Associate Professor, Department of Biomedical Engineering
University at Buffalo, the State University of New York
Abstract
The discovery of the anti-fibrosis treatments for pulmonary fibrosis is hampered by both limited understanding of the disease mechanism and the limited predicative capacity of the pre-clinical models. In this talk, I will introduce the biomimetic lung tissue fibrosis models created in my lab for modeling the disease progression and anti-fibrosis treatment in pulmonary fibrosis. Increased numbers of immune cells such as macrophages were shown to accumulate in the fibrotic lung, but it is unclear how they contribute to the development of fibrosis. To recapitulate the macrophage mechanical activation in the fibrotic lung tissue microenvironment, we developed a fibrotic microtissue model with cocultured human macrophages and fibroblasts. We show that profibrotic macrophages seeded on topographically controlled stromal tissue constructs become mechanically activated. The resulting co-alignment of macrophages, collagen fibers and fibroblasts promote widespread fibrogenesis in micro- engineered lung tissues. Anti-fibrosis treatment using pirfenidone disrupts the polarization and mechanical activation of profibrotic macrophages, leading to fibrosis inhibition. Pirfenidone inhibits the mechanical activation of macrophages by suppressing integrin αMβ2 (CD11b/CD18) and Rho-associated kinase 2, which is a previously unknown mechanism of action of the drug. Together, these results demonstrate a potential pulmonary fibrogenesis mechanism at the tissue level contributed by mechanically activated macrophages. We propose the cocultured, force-sensing microtissue model as a powerful tool to study the complex immune-stromal cell interactions and the mechanism of action of anti-fibrosis drugs.
Biography: Dr. Ruogang Zhao is an Associate Professor in the Department of Biomedical Engineering at the State University of New York at Buffalo. He earned his PhD in biomaterials and biomedical engineering from the University of Toronto and received his postdoctoral training in biological engineering at the Johns Hopkins University under the supervision of Dr. Daniel Reich and Dr. Christopher Chen. He started as an assistant professor at the University at Buffalo in 2013 and received tenure in 2019. Dr. Zhao is a bioengineer with a strong interest in developing advanced biofabrication technologies for disease modeling, drug discovery and damaged tissue repair. He has a particular clinical interest in fibrotic diseases and therapies. During his Ph.D. training, he received the prestigious Heart and Stroke Foundation of Canada Doctoral Research Award. He also received the 2019 Young Innovators Award of Cellular and Molecular Bioengineering from the Biomedical Engineering Society and American Lung Association Innovation Award in 2021.
Ke Yuan
Sep 22nd, 2023
Time: EST 9:00 pm; PST: 6:00 pm; Beijing time: Sep 23rd, 9:00 am
Engineered lung tissue models for modeling disease progression and anti-fibrosis treatment in pulmonary fibrosis
Ruogang Zhao Ph.D.
Associate Professor, Department of Biomedical Engineering
University at Buffalo, the State University of New York
Ke Yuan
Ke Yuan
Ke Yuan
Ke Yuan
Ke Yuan
Ke Yuan
Ke Yuan
Ke Yuan
Ke Yuan
CALA Happy Friday Seminar
Dec 1st, 2023
Time: EST 9:00 pm; PST: 6:00 pm; Beijing time: Dec 2nd, 10:00 am
Zoom: 849 9682 9273 (Password: 654321)
Molecular regulation of respiratory immune responses driving lung sequelae in Long COVID
Chaofan Li, PhD
Research Assistant Professor
University of Virginia
Biography: Dr. Chaofan Li currently serves as an Assistant Professor of Research in the Division of Infectious Diseases at the University of Virginia. He received his Ph.D. degree from Fudan University’s medical school. He obtained his postdoctoral training at the Mayo Clinic as a research fellow and research associate under the mentorship of Dr. Jie Sun. During this period, he focused on the transcriptional regulation of CD8 T cell’s epigenetic modification and metabolic process post influenza infection, using genetic methods that identified transcription factors critical for CD8 T cell’s function and fitness in non-lymphoid tissues. In 2022, he moved to the University of Virginia as a Research Assistant Professor. Since then, he has been dedicated to studying the cellular and molecular mechanisms that enable lung resident T cells to foster immune defense and aid tissue repair following viral pneumonia, including influenza and COVID-19. Through utilizing high throughput sequencing, comprehensive data analysis, and genetic modeling, he hopes to improve patient outcomes and advance the knowledge of immune responses to respiratory diseases.
Abstract: Respiratory postacute sequelae of SARS-CoV-2 infection (R-PASC), including disabling symptoms like dyspnea (incidence: 29.7%), cough (incidence: 13.1%), and interstitial lung disease (incidence varying from 7% to 30% with various symptoms), can persist for more than 2 years (possibly longer) in some COVID-19 convalescents. While studies have linked aberrant peripheral immune responses to the symptoms observed in R-PASC6-9, our understanding of the respiratory immune status driving R-PASC remains fragmented. Additionally, relying solely on observational clinical studies limits our ability to discern causative mechanisms from mere correlative associations, making employing animal research for a deeper understanding of R-PASC's driving factors imperative. In our recent study, we have made comprehensive comparisons between bronchoalveolar lavage fluid (BAL) single-cell RNA sequencing (scRNAseq) data derived from clinical PASC samples and relevant R-PASC mouse models. This revealed a strong pro-fibrotic monocyte-derived macrophage response in respiratory PASC (R-PASC) in both humans and mice, and abnormal interactions between pulmonary macrophages and respiratory resident T cells. IFN-γ derived from respiratory resident T cells emerged as a key node mediating the immune anomalies in R-PASC. Strikingly, neutralizing IFN-γ post the resolution of acute infection reduced lung inflammation and tissue fibrosis, and improved pulmonary gas-exchange function in two mouse models of R-PASC. Our study underscores the importance of performing comparative analysis to understand the root cause of PASC for developing effective therapies.
Ke Yuan
Ke Yuan
Ke Yuan
CALA Happy Friday Seminar
Dec 8th, 2023
Time: EST 9:00 pm; PST: 6:00 pm; Beijing time: Dec 9th, 10:00 am
Zoom: 849 9682 9273 (Password: 654321)
Host Resilience to obesity-induced diabetes and Diabetes-associated Vascular Complications
Qing Robert Miao, Ph.D.
Professor
Diabetes and Obesity Research Center
New York University Grossman Long Island School of Medicine
Biography: Dr. Qing Robert Miao is well recognized for his research on elucidating the biological functions of Nogo-B receptor and its roles in the pathogenesis of human diseases. Nogo-B receptor (NgBR) is a cell surface receptor that was identified by Dr. Miao during his postdoctoral training in Dr. William Sessa’s laboratory at the Yale School of Medicine. His continuous work at the Medical College of Wisconsin demonstrated that NgBR is a vital gene required for the development and loss of NgBR causes early embryonic lethality. In 2019, Dr. Miao was recruited to NYU Grossman Long Island School of Medicine.
Dr. Miao’s significant contribution to science is elucidating the unique properties of NgBR binding prenylated Ras and regulates Ras plasma membrane translocation, which is an important cell process required for many receptor tyrosine kinase-mediated pathways. This innovative discovery not only reveals why NgBR is an essential gene for development but also opens a new research avenue in developing a new therapeutic approach targeting the concurrent receptor tyrosine kinase-mediated tumorigenic pathways.
Dr. Miao’s innovative research program successfully connects their bench work with human diseases and strengthens the translational aspect of their research through collaboration with clinical colleagues. Based on the determination of physiological defects occurring in NgBR tissue-specific knockout mice, Dr. Miao’s research team successfully established several unique animal models for elucidating the novel underlying mechanisms of human diseases, such as cerebrovascular malformations, nonalcoholic fatty liver diseases, and obesity-induced diabetes. Dr. Miao’s career establishment is evidenced by the continuous success of NIH funding and the Mid-Career Investigator Award from the American Heart Association’s Council on Peripheral Vascular Disease.
Ke Yuan
Ke Yuan
Ke Yuan
Ke Yuan
CALA Happy Hour 1/19/24 在线讲座 Dr. Zi Chen
Ke Yuan
Ke Yuan
Ke Yuan
CALA Happy Friday Seminar
Feb 16th, 2024
Time: EST 9:00 pm; PST: 6:00 pm; Beijing time: Feb 17th, 10:00 am
Zoom: 849 9682 9273 (Password: 654321)
Application of dual recombinases for the study of lung stem cells and regeneration
Bin Zhou, MD & PhD
Professor and New Cornerstone Investigator
Chinese Academy of Sciences
Biography: Dr. Bin Zhou received MD degree from Zhejiang University School of Medicine in 2002, and PhD degree from Peking Union Medical College in 2006. From 2006-2010, Dr. Zhou did his postdoctoral fellowships at Boston Children’s Hospital with Bill Pu. In 2010, Dr. Zhou became a professor at the Chinese Academy of Sciences. The major goal of his lab is to develop new lineage tracing technologies and apply them to understand better the origin, heterogeneity, and fate plasticity of cell lineages during organ development, regeneration, and diseases.
Abstract: This presentation will introduce recently developed genetic lineage tracing approaches and research advances, giving examples of their applications in the study of lung stem cells and regeneration. Specifically, we used dual recombinase-mediated genetic lineage tracing to uncover the contribution of bronchioalveolar stem cells (BASCs) to airway and alveolar epithelial cells after lung injury. Additionally, dual recombinases-mediated intersectional genetic approach has been used to reveal the origin of alveolar type 2 (AT2) cells during lung repair and regeneration. Distinctive, but simultaneous, labeling of club cells, bronchioalveolar stem cells (BASCs), and AT2 cells revealed the exact contribution of each to AT2 cells after lung injury. This intersectional genetic lineage tracing strategy with enhanced precision allowed us to elucidate the physiological role of distinct epithelial cell populations to alveolar regeneration after injury.
Ke Yuan
Ke Yuan
CALA Happy Friday Seminar
March 8th , 2024
Time: EST 9:00 pm; PST: 6:00 pm; Beijing time: March 9th, 10:00 am
Zoom: 849 9682 9273 (Password: 654321)
Endocardial Biology in Heart Development and Disease
Bin Zhou MD PhD
Professor
Department of Pediatrics
The University of Chicago
Bio: Dr. Bin Zhou earned an MD from Nanjing Medical University in China and completed his residency in internal medicine and cardiology at the First Affiliated Hospital of Nanjing Medical University. He received a PhD in cardiovascular pathobiology from the University of Toronto. He then pursued a fellowship in cardiovascular development and mouse genetics at the University of Pennsylvania School of Medicine. Previously, he was an assistant professor of pediatrics at the University of Pennsylvania, and later at Vanderbilt University. In 2008, He was recruited to the Albert Einstein College of Medicine as an associate professor and later promoted to professor of genetics, pediatrics, and medicine in 2013. In 2023, Bin joined the Department of Pediatrics at the University of Chicago as a tenured full professor.
Bin’s research focuses on endocardial biology in heart development, disease, and regeneration. His research goal is to understand the molecular mechanism controlling the specification and differentiation of the endocardial cells, and its involvement in the pathogenesis of congenital heart defects and coronary artery anomalies. He has published over 100 papers in journals including Cell, Nature Cell Biology, Nature Communications, Developmental Cell, European Heart Journal, and Circulation Research.
Abstract: The endocardium is the innermost endothelial layer of the heart chambers. In addition to expressing genes common for all the endothelial cells, endocardial cells express genes unique to themselves, implying their heart-specific gene regulation and functions. In this seminar I will discuss endocardial functions in heart development and disease. Using mouse models, I will first examine the endocardial-dependent formation of heart valves that relates to bicuspid aortic valve, as well as aortic valve stenosis – a common aging disease. I will then apprise the endocardial origin of coronary vessels that relates to coronary artery anomaly – a congenial disease with severe cardiac complications. Besides the endocardium, I will touch upon the myocardium and end my seminar by introducing a new mouse model for better elucidating the cardiac gene program in heart development and disease.
Ke Yuan
Ke Yuan
Ke Yuan
Ke Yuan
Ke Yuan
Ke Yuan
Ke Yuan
CALA Happy Friday Seminar
April 12nd , 2024
Time: EST 9:00 pm; PST: 6:00 pm; Beijing time: April 13rd, 9:00 am
Zoom: 849 9682 9273 (Password: 654321)
Regulation of alveolar progenitor self-renewal in repair and cancer
Jessie Huang, PhD
Assistant Professor
University of Southern California
Bio: Dr. Jessie Huang is an Assistant Professor at the Hastings Center for Pulmonary Research, Keck School of Medicine at the University of Southern California. She earned her Ph.D. in environmental health and engineering from Johns Hopkins University and completed her postdoctoral training in stem cell biology in the laboratory of Dr. Darrell Kotton at Boston University and Boston Medical Center. She started her lab in 2024, focusing on the study of biological processes and signaling pathways that affect lung progenitor responses to injury. Dr. Huang’s lab integrates the use of human iPSCs-derived platforms with genetic mouse models to study how and why alveolar progenitor cell function is dysregulated in diseases such as acute respiratory distress syndrome and lung adenocarcinoma.
Abstract: Alveolar epithelial type 2 cells (AT2s) are facultative progenitors that are normally quiescent in the uninjured adult lung, but can remarkably reenter cell cycle upon injury. While this process has been observed in animal models, healthy non-aberrant AT2 self-renewal, as well as aberrant cancerous AT2 self-renewal, have not been thoroughly studied in the adult human lung. To investigate what factors control human AT2 self-renewal, we use an in vitro human induced pluripotent stem cell (iPSC)-derived AT2 (iAT2) model, in which putative AT2-like cells have robust self-renewal capacities when maintained in feeder-free 3D epithelial-only sphere cultures. Characterization of this model, in addition to an in vivo mouse model of AT2-specific injury, has provided insight on the shared transcriptional alterations, including enhancer of zeste homolog 2 (EZH2), occurring in self-renewing AT2s/iAT2s. Additionally, iAT2s can be engineered to harbor inducible oncogenes, such as KRASG12D, to model diseases such as lung adenocarcinoma whereby AT2 self-renewal is dysregulated. Oncogene-mutated iAT2s display aberrant phenotypes of reduced AT2 maturation and increased progenitor markers, similar to lung adenocarcinoma patient samples. These data suggest that understanding the balance between maturation and proliferation is essential to elucidating how the lung effectively or ineffectively repairs itself.
Ke Yuan
Ke Yuan
Beiyun Zhou
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Beiyun
Hongpeng Jia
Hongpeng Jia
Associate Professor
Division of Pediatric Surgery
Department of Surgery
Graduate Faculty
Pathobiology Graduate Training Program
Johns Hopkins University School of Medicine
Office: 735A Ross Building
Tel: 410-955-3429
Lab: 733 Ross Building
Tel: 410-614-0568
1721 E Madison Street
Baltimore, MD 21205
Email: hj...@jhmi.edu
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Ke Yuan
CALA Happy Friday Seminar
May 24th , 2024
Time: EST 9:00 pm; PST: 6:00 pm; Beijing time: April 13rd, 9:00 am
Zoom: 849 9682 9273 (Password: 654321)
The Golgi apparatus as a therapeutic target in lung cancer
Xiaochao Tan, PhD
Assistant Professor
Tulane University School of Medicine
Bio: Dr. Xiaochao Tan is an Assistant Professor at the School of Medicine at the Tulane University. He earned his Ph.D. in Molecular Biology and Biochemistry from Chinese Academy of Medical Sciences and Peking Union Medical College and completed his postdoctoral training at University of Texas MD Anderson Cancer Center. Dr. Tan started his lab in 2023, focusing on the study of dysregulation of the Golgi apparatus in driving the initiation and progression of cancer.
Abstract: The dysregulation of the Golgi apparatus has emerged as a significant factor driving the initiation and progression of cancer. Investigating the mechanisms by which oncogenic somatic mutations impact the structure and secretory functions of the Golgi organelle is crucial for understanding the role of the Golgi secretory pathway in lung cancer progression. Our research endeavor aims to pave the way for the development of innovative therapeutic approaches grounded in a deeper comprehension of these processes.
Ke Yuan
CALA Happy Friday Seminar
June 7th , 2024
Time: EST 9:00 pm; PST: 6:00 pm; Beijing time: June 8th, 9:00 am
Zoom: 849 9682 9273 (Password: 654321)
Vascular Involvement in Viral Lung Injury and Repair
Gan Zhao, PhD
Postdoctoral Researcher
University of Pennsylvania
Bio: Dr. Gan Zhao is currently conducting postdoctoral research at the University of Pennsylvania under the joint supervision of Dr. Edward Morrisey and Dr. Andrew Vaughan. Gan obtained his PhD from Huazhong Agricultural University in China and joined Dr. Vaughan's lab in September 2018 as a visiting student, transitioning to a postdoctoral position in July 2020. In 2023, Gan joined Dr. Morrisey's lab. His research focuses on uncovering the underlying molecular and cellular mechanisms by which the lung vascular endothelium is able to repair and regenerate, especially in the context of viral lung injuries such as influenza and COVID-19. Additionally, Gan investigates the somewhat unexpected role of endothelial-derived signaling molecules ("angiocrine" factors) in modulating the inflammatory response to these infections.
Abstract: We focused on the vascular repair mechanisms in viral pneumonia, conducting basic and translational research. Utilizing single-cell transcriptomic sequencing, lineage-tracing mice, conditional gene knockout or overexpression mice, vascular organoids, and lipid nanoparticles, we demonstrated that the newly regenerated endothelial cells (ECs) in viral injuries primarily occurs through the angiogenic proliferation of pre-existing ECs. This process is orchestrated by key regulators such as the transcription factor COUP-TF2 and TGFBR2-mediated signaling. Specifically, COUP-TF2, predominantly expressed in venous endothelium, regulates endothelial migration and proliferation by driving expression of cell cycle genes CCND1 and VEGFA-signaling mediator NRP1. Additionally, TGFBR2 signaling is essential for the renewal of a specific lung capillary subset, CAR4+ECs, also referred to as aerocytes. We then developed lipid nanoparticles (LNPs) targeting lung vasculature, demonstrating their potential for clinical application in treating lung diseases. Further studies revealed that lung endothelial cells activated by injury produce high levels of SPARCL1, a protein that intensifies inflammation in viral pneumonia. Increased SPARCL1 levels in the plasma of COVID-19 patients who died compared to those who recovered suggest its potential as a biomarker for lung injury progress. We elucidated a novel mechanism that endothelial-derived SPARCL1 exacerbates lung injury and inflammation by continuously recruiting and activating alveolar macrophages. Overall, our findings suggest that targeting pulmonary vasculature could offer new therapeutic avenues for clinical conditions, including viral pneumonia and other pulmonary diseases.