The Division of Pulmonary and Critical Care Medicine is distinguished for its world-renowned clinical, basic, and translational investigators in multiple areas, including chronic obstructive pulmonary disease (COPD), interstitial lung disease (ILD), pneumonia, and idiopathic pulmonary fibrosis (IPF). Current COPD and IPF research in PCCM focuses on the disease's appropriate and early diagnosis, biological underpinnings, and personalized approaches to innovative therapeutic strategies. Additional research in PCCM is involved in defining the immunological basis of acute exacerbations, the role of the pulmonary lymphatic vasculature on lung homeostasis, and the regulation of extracellular and cell-mediated matrix turnover pathways. PCCM investigators employ state-of-the-art techniques to identify and correlate candidate genes and mechanistic processes in acute and chronic lung disease pathogenesis.
Dr. Robert Kaner serves as the Principal Investigator of the Weill Cornell Medicine site of the Pulmonary Fibrosis Foundation Care Center Registry. He was the site PI of Idiopathic Pulmonary Fibrosis (IPF) Clinical Research Network, where he chaired the Adjudication Committee for IPFnet, and in that capacity, has collaborated productively with Dr. Fernando Martinez. He was the project leader of an NIH-sponsored study of the molecular basis of accelerated emphysema development in HIV-1 positive smokers. He has served as Principal Investigator of an NIH-sponsored basic research study on the mechanisms of vascular permeability in the lung and interactions of human alveolar macrophages with HIV-1. Dr. Kaner's research is noted for the application of cutting-edge molecular techniques to study human lung diseases. Dr. Kaner's work has identified matrix metalloproteinase upregulation in the lung as a potential contributor to early emphysema in HIV-positive individuals. He and collaborators within the infectious disease division performed a pilot study to determine if doxycycline can reduce lung matrix metalloproteinase activity in HIV-positive individuals with COPD and/or emphysema and has a clinical trial proposal pending. He has shown that high levels of VEGF protein are compartmentalized to the epithelial lining fluid in normal humans. He is the PI of the Pulmonary Biobank. He is the overall PI of a multi-center observational study of ILD following COVID-19 infection.
Dr. Michael Niederman is an international authority on respiratory infections. He has been engaged globally in the development of diagnostic and therapeutic guidelines for the management of community acquired and hospital acquired pneumonias. He has an active investigative portfolio examining novel therapeutic options for respiratory infections, including complex respiratory infections in the intensive care unit. He is currently leading an international multi-center study of the use of adjunctive aerosolized antibiotics for the therapy of severe pneumonia. He is also focused on an investigative portfolio leveraging antimicrobial stewardship by enhancing the optimal therapeutic approach to respiratory infections in the ICU while minimizing antimicrobial resistance. Recently, he has become involved in a multi-disciplinary study to examine the long-term sequelae of COVID-19 infection.
Dr. Hasina Outtz Reed studies the role of the pulmonary lymphatic vasculature on chronic lung disease and lung homeostasis. While it has been known for quite some time that lymphatics are present and likely important for lung function, tools for testing whether the lymphatics play a role in lung pathology and for targeting these vessels have been lacking. Dr. Outtz Reed has developed novel mouse models for impaired pulmonary lymphatic flow and is among the first to have shown a direct connection between lymphatic dysfunction and lung injury. Ongoing work will investigate how underlying lymphatic dysfunction affects the lung’s response to injury and the mechanism by which it occurs. Furthermore, her work will develop innovative methods for imaging and modifying the pulmonary lymphatics with the hope that these tools will translate to the ability to target these vessels therapeutically.
Dr. Renat Shaykhiev, who recently joined the pulmonary division, is focused on airway epithelial stem cells, differentiation pathways and plasticity; epithelial-mesenchymal interactions, using 3D airway organoid models that mimic organization of human airways in the in vivo lung; epithelial-immune interactions and innate immunity in the lung; and pathogenesis of airway remodeling in human lung disease. The latter line of study uses patient-derived models of airway epithelial differentiation and remodeling to study the molecular and cellular mechanisms that underlie the early pathogenesis of airway remodeling in human lung diseases, such as COPD, asthma, pulmonary fibrosis and lung cancer.
Dr. Suzanne Cloonan, studies programmed cell death (PCD) pathways in the pathogenesis of disease states. She first identified a non-canonical form of PCD involving autophagy as a mechanism of action pertaining to particular anti-depressant drugs. Her advances in research include: showed a mechanism by which cilia of the airway epithelium shorten in response to cigarette smoke as related to COPD pathogenesis; showed in vitro and in vivo, that cigarette smoke induces mitochondrial dysfunction in the lung, leading to selective removal of mitochondria by PINK-1 dependent autophagy or mitophagy; and identified a GWAS COPD susceptibility gene in the regulation of mitochondrial responses to cigarette smoke.
Dr. Heather Stout-Delgado, focuses on the impact of aging on innate immune responses to bacterial and viral pulmonary infections. Her laboratory is also examining how the process of biological aging and dysregulated molecular signaling pathways can contribute to the development of pulmonary fibrosis. Using both in vitro and in vivo models, her laboratory is critically examining cellular and molecular signaling cascades with the goal to design therapeutic strategies to improve these responses in the aged lung.
The Critical Care section of the Division of Pulmonary and Critical Care Medicine is at the forefront of advances in research that are benefiting the clinical care setting, such as the Intensive Care Unit. Studies underway cover a wide breadth, from sepsis to lung and brain injury, and are carried out by individual investigators or in collaboration with outstanding researchers from other divisions within the Weill Department of Medicine.
The Division is currently conducting two FDA approved Phase II clinical trials investigating both sepsis and IPF. Regarding the treatment of sepsis-induced ARDS (acute respiratory distress syndrome), we are leading an NIH-sponsored Phase I trial.
There are numerous other lines of sepsis study in the division, that include: the role of heart rate variability in early sepsis, the role of the endothelium and coagulation, symptom management in critically ill patients, the role of endothelial micro-particles, and the roles of autophagy, mitochondrial DNA and the inflammasome.
Drs. Ed Schenck, Luis Gomez-Escobar, David Price, John Harrington, and Lisa Torres lead a biobank of critical illnesses. The registry contains detailed phenotypic information and biologic specimens with a focus on the evaluation of damage-associated molecular patterns in critical illness.
Additional investigations in the area of critical care include: physiology of cardiac output monitors and novel ventilation strategies, the outcomes of difficult airway management and bronchoscopy in critically ill patients, physiology of cardiac output monitors and novel ventilation strategies, clinical significance of hemodynamic waveforms, models of ventilator induced lung injury, and ischemic-anoxic brain injury.
Dr. Michael Niederman, the Division of Pulmonary and Critical Care Medicine Clinical Director, is leading a study on ventilator-associated pneumonia.
As the population continues to live longer in the U.S., the division remains focused on pulmonary infections and pulmonary fibrosis as related to aging. Influenza viral infections are responsible for annual epidemics that cause severe morbidity and mortality worldwide. It is imperative to elucidate how aging modifies innate immunity and contributes to viral persistence and increased susceptibility to secondary bacterial infections. Researchers in the division are investigating the impact of biological aging on innate immune responses to primary viral and bacterial pulmonary infections, with the goal to design and evaluate therapeutics to improve these responses in the aged lung.
Aging is associated with declined mitochondrial energy metabolism, enhanced mitochondrial oxidative stress, increased production of mitochondrial reactive oxygen species (mtROS), and accumulated mitochondrial DNA mutations. Low levels of inflammation, due to enhanced mitochondrial dysfunction and oxidative stress, can potentiate inflammatory responses associated with many age-related degenerative diseases. Fibrotic interstitial lung diseases, which are severe and progress rapidly, and include idiopathic pulmonary fibrosis (IPF), are more prevalent in aging populations. A sharp increase is seen in these diseases for those older than 50 years.
Little is known of how oxidative stress, mitochondrial dysfunction and the process of aging may contribute to disease pathogenesis. Researchers in the division are investigating the cellular and molecular pathways that underlie enhanced fibrotic lesion development in aged lungs, with the goals of designing and evaluating therapeutic treatment strategies to improve lung function in older populations.
