Research in COPD

Dr. Naftali Kaminski is, as of July 1st, 2013, the Boehringer-Ingelheim Endowed Professor of Internal Medicine and Chief of Pulmonary, Critical Care and Sleep Medicine, at Yale School of Medicine. Before that he was a tenured professor of Medicine, Pathology, Computational Biology and Human Genetics, and the Dorothy P. and Richard P. Simmons Endowed Chair for Pulmonary Research at the University of Pittsburgh. Dr. Kaminski was the director of the Dorothy P. and Richard P. Simmons Center for Interstitial Lung Disease and the Lung, Blood and Vascular Center for Genomic Medicine at the division of Pulmonary, Allergy and Critical Care Medicine in University of Pittsburgh. Dr Kaminski received his medical degree from the Hebrew University - Hadassah Medical School in Jerusalem, Israel, and completed a residency in Internal Medicine at Hadassah Mount-Scopus University Hospital in Jerusalem, and a fellowship in pulmonary medicine at Sheba Medical Center in Tel-Hashomer, Israel. Dr Kaminski received his basic science training in Dean Sheppard's laboratory at the Lung Biology Center at UCSF and in functional genomics and microarray technology at the Functional Genomics laboratory at Roche Bioscience, Palo-Alto. After his fellowship in 2000, Dr. Kaminski was appointed head of Functional Genomics at Sheba Medical Center in Israel, before being recruited to head the Simmons Center at the University of Pittsburgh in 2002.Dr. Kaminski's main research interests involve applying genomic approaches to elucidate basic mechanisms and improve diagnosis and treatment of Idiopathic Pulmonary Fibrosis (IPF), a chronic mostly lethal and currently untreatable scarring lung disease and other chronic lung diseases such Chronic Obstructive Pulmonary Disease (COPD), severe asthma and sarcoidosis. His group pioneered the application of high throughput genome scale transcript profiling in advanced lung disease. Among his key scientific achievements are: The discovery of novel molecules  with significant active roles in pulmonary fibrosis, including matrix metalloproteases (MMP7, MMP19) and phosphatases (SHP2, MKP5) , demonstrating that microRNAs, a family of small non-coding RNAs, are differentially expressed in IPF, and that some of them (let-7, mir-29, mir-33) are mechanistically involved in lung fibrosis, and the discovery that the outcome of patients with IPF can be predicted based on the expression of peripheral blood proteins and genes, a finding with practical implication because of the need for risk stratification and transplant prioritization. More recently Dr. Kaminski's team identified a potential antifibrotic role for thyroid hormone signaling, a novel discovery with significant therapeutic implications, and performed single cell RNA sequencing on >300,000 cells obtained from patients with advanced lung disease and created an online freely available data dissemination tool (www.IPFCellAtlas.com). Dr. Kaminski has a strong interest in integrating high throughput ‘omics’ data, such as genome scale DNA variants, coding and non-coding RNAs, microbiome and metabolome information with clinical information to generate systems biology models of lung diseases and to develop precision medicine approaches that are significantly more precise, predictive and patient-centered than anything that is currently available.Since completing his clinical training, Dr. Kaminski authored more than 340 research papers (including in Nature Medicine, NEJM, Nature Genetics, Nature Communications, PNAS, Science Advances, Science Translational Medicine, Circulation, Lancet Respiratory Medicine, ARCCM and ERJ among others) review articles and book chapters and has given numerous invited talks at national and international conferences, review articles and book chapters and has given numerous invited talks at national and International conferences. Since he finished his fellowship in 2000, Dr. Kaminski has been consistently funded by NIH and is the PI of multiple NIH grants. Dr. Kaminski was a recipient of the Marvin I. Schwarz Award for contributions to patient care and research in pulmonary fibrosis from the Coalition for Pulmonary Fibrosis in 2010 and the University of Pittsburgh Innovator Award in 2012. In 2013, Dr. Kaminski received the American Thoracic Society Recognition of Scientific Achievements award, as well the Helmholtz Institute International Fellow. In 2015 he was elected to the Association of American Physicians. In 2016 he was elected as Fellow of the European Respiratory Society (ERS), and won   the European Respiratory Society Gold medal for Interstitial Lung Disease. In 2018, Dr. Kaminski received the Andy Tager Excellence in Mentorship Award from the Respiratory Cell and Molecular Biology Assembly of the American Thoracic Society and was elected fellow of the American Thoracic Society and received the Yale Blavatnik Innovation Award. In 2022 Kaminski received the American Thoracic Society Amberson Lecture award.  Dr. Kaminski is active on the ATS and was the editor of “Gene Express”, a column on genomics in the initial days of the ATS Website, a member and chair of the Program Committee of the Assembly on Respiratory Cell and Molecular Biology of the ATS, and member of the ATS Research Advocacy Committee, and Chair of the Assembly on Respiratory, Cell, and Molecular Biology at the American Thoracic Society. He was an associate editor of the American Journal of Respiratory and Critical care Medicine, a member of multiple editorial boards and recently the Deputy Editor of Thorax, BMJ. Dr. Kaminski served as the President of the Association of Pulmonary, Critical Care and Sleep Division Directors in 2019. Dr. Kaminski is passionate about training physician-scientists for the challenges of 21st century medicine, and especially in the vocabulary, skills and technology of the new fields of genomics, bioinformatics, computational and system biology and their application to understanding the basic mechanisms that govern lung health and disease as well as to designed personalized medicine approaches and has mentored multiple MD and PhD scientists, of them many have productive and well funded independent career. He has most recently recognized for his commitment to mentoring with the American Thoracic Society Andy Tager excellence in mentoring award.Follow Dr. Kaminski on Twitter @kaminskimed Follow Dr. Kaminski on mastodon @kaminskimed@med-mastodon.com<a rel="me" href="https://med-mastodon.com/@Kaminskimed">Mastodon</a>

Dr. Dela Cruz completed his research training through an MD/PhD program in the area of immunology and virology from University of Toronto and Yale. Clinically, he is trained in internal medicine, and specializes in pulmonary and critical care medicine and is currently an Associate Professor at Yale University in the same department. He is also the founding director for the Center for Pulmonary Infection Research and Treatment (CPIRT). www.cpirt.yale.edu. His laboratory is interested in studying the role of respiratory infection in the pathogenesis of acute and chronic lung diseases. Specifically, his work focuses on how lung infection contribute to inflammation, injury and tissue repair in the lung. This has allowed the lab to carefully study the molecular and cellular responses of several novel mediators in the lung.His laboratory focuses on two main research programs. (1) Studying novel immune regulators in the lung during respiratory infections. (2) Studying the effects of cigarette smoke (CS) exposure in the pathogenesis of airway and lung diseases such as chronic obstructive pulmonary disease (COPD) using preclinical genetic mouse models and human biosamples. The goal of the lab is also to be able to confirm and translate the findings using biospecimens from the established and establishing cohort of human patients with various lung diseases.COPD is a composite entity that includes chronic bronchitis and emphysema, is a leading cause of death in the world, and is a disease that is in need of new treatments. One of the goal of our laboratory is to investigate the interaction between CS and respiratory virus infection in the pathogenesis of COPD and identify novel therapeutic targets for this respiratory disease. It has been long thought that the frequent respiratory infections in COPD patients are due to their depressed immune function. Our studies have revealed that CS-exposed hosts have an over-exaggerated immune reaction to viral infections. Frequent acute COPD exacerbations correlate with increased rate of disease progression and more loss of lung function in COPD especially if it is due to viral infections. Our studies have shown that CS exposure has an impressive ability to regulate the innate immunity in the lung after influenza virus and respiratory syncytial virus (RSV) infection. CS enhances the inflammation, alveolar destruction and airway fibrosis caused by influenza virus and RSV. These effects are mediated by type I interferon and RIG-like helicase antiviral innate immune pathway. CS exposure also results in the induction of interleukin-15 in the setting of these respiratory infections. We hypothesize that these novel mechanistic pathways may explain the heightened inflammatory response and worsening lung functions in COPD patients with multiple virally-induced exacerbations, and the chronic lung inflammation seen in stable COPD patients. We have also translated our findings by studying these immune mediators in patients infected with various respiratory viruses and have thus far collected >300 human biosamples.YCCI Scholar 2011

Maor Sauler has been a member of the Pulmonary & Critical Care faculty since 2014. Dr. Sauler specializes in adult critical care including acute lung injury and sepsis. He also sees patients in the outpatient setting with pulmonary diseases such as Chronic Obstructive Pulmonary Disease (COPD). Dr. Sauler is board-certified in internal medicine, pulmonary medicine, and critical care medicine. Dr. Sauler earned his undergraduate degree from Princeton University and received his MD from Rutgers-New Jersey Medical School. Dr. Sauler then completed both an internship and residency in internal medicine at Yale-New Haven Hospital. He went on to complete fellowship training in pulmonary and critical care medicine at Yale-School of Medicine.Dr. Sauler investigates mechanisms of lung injury and cytoprotection by integrating findings from high-throughput sequencing technologies with murine and in vitro models of chronic lung disease. Specifically, he is focused on identifying cellular stress responses that change with age or with COPD, and understanding how these mechanisms  contribute to disease susceptibility or maintain lung "resilience". By studying the impact of aberrant cellular stress responses on lung injury, inflammation, and repair, Dr. Sauler hopes to identify novel therapeutic targets for patients with COPD.

My prior studies focused on the pathogenesis of cigarette-smoke (CS) -induced lung diseases such as chronic obstructive pulmonary disease (COPD), wherein we demonstrated that the IL-18 system plays an important role in the pathogenesis of CS-induced emphysematous lung destruction. These studies led me to question the effect of CS on innate immunity on the interaction between the host and microorganisms and, for this purpose, I had established a murine cigarette smoke and virus co-exposure model. These studies revealed important insight into the interaction between CS and the innate immunity resulting in a publication in the Journal of Clinical Investigation. In that study, we identified that CS smoke selectively augments respiratory antiviral innate immune responses via a MAVS-RLHs antiviral signaling pathway. To gain better understanding of the mechanisms, my laboratory is focusing on the role(s) of mitochondrial dysfunction and immune dysregulation in the setting of smoking exposure. By applying recent state-of-art knowledge of mitochondrial biology, our research goal is to establish mitochondrial dysfunction and mitochondrial injury/damage responses as a key event in the pathogenesis of COPD and CS-and virus-associated disorders and as such, to provide a new perspective of our understanding of COPD and CS-and virus-associated disorders.