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Basic and Translational Research

The Division of Pulmonary and Critical Care Medicine at Northwestern University Feinberg School of Medicine is among the leading groups in the world in the field of lung biology and clinical research in lung diseases. 

Our research programs are anchored on large collaborative multi-investigator projects that blur traditional distinctions between basic science and translational research.  We start with the patient.  Clinical scholars and epidemiologists identify critical research questions and generate hypotheses from high-quality observational data.  Clinicians in our specialty program identify pathways by which these questions can be addressed as part of clinical care.  They collect samples from the lung as and provide them to our team of laboratory scientists.  Investigators in our state-of-the art laboratories analyze these samples using novel genomic and clinical phenomic approaches.  Data scientists in our group integrate data from these patients to identify hypotheses about disease mechanisms.  Basic science researchers in our Division use cell and animal models to causally test these hypotheses and identify small molecules for therapy. Our clinical researchers test these or related drugs in interventional trials conducted in our clinical specialty programs. 

 Acute Lung Injury

Acute Lung Injury is a devastating disorder that affects nearly a quarter million people in the United States annually.  Dr. Sznajder and Dr. Corbridge along with other investigators in our Division have made seminal contributions to our understanding of the physiology of ARDS that have led to advances in the supportive care of these patients.  Despite these advances, however, therapies that directly target the disease pathobiology remain elusive.  Our group is focused on understanding the molecular mechanisms by which activation of the innate and adaptive immune response alter alveolar epithelial function in the injured lung.  Our basic laboratory work is strongly linked with our clinical studies in the MICU that focus on pneumonia as among the most common causes of ARDS.  Please explore some of the research programs focused on ARDS in our group and the laboratories leading these studies.

 Asthma

Asthma is a major cause of morbidity in both adults and children.  In urban areas like Chicago, asthma prevalence exceeds 10%.  Decades of research have identified a host of effective therapies that have transformed the health of many patients with asthma.  Nevertheless, many patients respond poorly to therapy and the underlying molecular drivers of the disease are not known. Our group interact closely with the substantial investigative team in Allergy and Immunology led by Dr. Robert Schleimer to study the pathobiology of asthma. 

 Chronic Obstructive Pulmonary Disease (COPD)

While the mortality attributable to many chronic diseases has declined, that attributable to COPD has continued to increase and COPD has overtaken stroke as the third leading cause of death in the US. While the contributions of environmental factors particularly cigarette smoke to COPD pathogenesis are recognized, continued research reveals a complex interplay between these factors and the innate immune system in the lung.  Understanding these factors might not only provide novel strategies to treat or prevent COPD, but also to identify factors that promote lung resilience with implications for aging.  Our group has focused on interactions between the environment, the lung epithelium and alveolar macrophages to better understand COPD pathogenesis, particularly in the context of advancing age.

 Environmental Lung Disease

The human lung is charged with the dynamic maintenance of oxidative phosphorylation in all of the tissues of the body through the efficient transport of oxygen and carbon dioxide between the blood and the ambient air.    To accomplish this goal, the epithelial surface of the airways and alveoli is directly exposed to the nearly a quarter billion liters of air enters and leaves the lung over an average human lifespan.  This air contains environmental particulates and toxins including cigarette smoke, particulate matter air pollution and asbestos, all of which can contribute to the development of chronic lung disease.  Our group is focused on understanding the mechanisms by which the lung responds to these environmental challenges and how these responses may contribute to the development of chronic lung disease.

 Lung Aging

Age is such an important and seemingly inevitable risk factor for disease that it is often overlooked in clinical practice. Yet expected rapid growth in the population of elderly, including a projected tripling in the size of the global population over 80 years old by 2050, mandates a better biologic understanding of the intersection between the biology of aging and the susceptibility to disease. The changes that develop in the lung during “normal aging” show remarkable similarities to the pathologies evident in patients with COPD and pulmonary fibrosis. It therefore seems likely that interventions that would slow the normal age-related decline in lung function and increase lung resilience would have a dramatic effect on the morbidity attributable to chronic lung disease.  

Our group is actively engaged in research to understand how the biology of aging intersects with that of chronic lung disease. We are particularly focused on proteostasis, the dynamic process by which cells control the concentration, conformation, binding interactions, and location of individual proteins making up the proteome through a system of regulated networks of interacting and competing biological pathways that influence protein synthesis, folding, trafficking, disaggregation, and degradation. In C. elegans, a systemically coordinated genetic program is activated upon fecundity that results in a progressive decline in the function of the proteostasis network. Genetically interrupting this process results in a prolonged lifespan with enhanced stress resilience. We are using combined approaches including imaging, transcriptomics, proteomics and epigenomics to define the function of the proteostasis network in the lung with age in comparison with other organ systems and to identify factors that might enhance proteostasis over the lifespan. 

 Lung Cancer

Lung cancer is the leading cause of cancer death worldwide and curative therapies have remained elusive.  Our group, led by Dr. Navdeep Chandel, has made seminal contributions to the field of cancer metabolism, opening novel areas for therapy.  

 Lung Immunology

Over the lifespan, the human lung is exposed to nearly a quarter billion liters of ambient air, which carries with it a host of environmental contaminants.  The innate and adaptive immune system in the lung is charged with distinguishing harmless contaminants from potentially lethal pathogens and mounting an appropriate immune response.  Our group is focused on the role of the innate and adaptive immune systems in the development of chronic lung diseases.  In our work, we collaborate closely with investigators in Rheumatology, led by Dr. Harris Perlman and with other investigators in the Northwestern Research Community.  Examples of our ongoing projects are described below.

 Lung Regeneration

The lung has a remarkable ability to repair itself after injury.  Recent investigations from several groups have revealed a complex system of progenitor cells in the lung responsible for repair after injury. 

 Metabolism

Since the advent of the genomic era, diseases have been understood as disorders of genes and their encoded transcripts and proteins, while metabolism has been considered a necessary adjunct to fuel these processes.  In the last decade, our group has made important contributions toward understanding some diseases a primary disorders of metabolism.  In this model, changes in metabolism induce signaling events that induce changes in gene expression or protein function.   Our metabolism group is led by Dr. Navdeep Chandel, and extends to almost all aspects of our research program. 

 Pediatric Lung Disease

Our group interacts closely with our colleagues in Neonatology and Pediatrics.  We have had the pleasure of hosting several pediatric and neonatology fellows in our laboratories and have active ongoing collaborations.

 Pneumonia

Pneumonia is a common cause of ARDS and is a common complication of critical illness.  We have an active clinical research program in pneumonia, led by Dr. Richard Wunderink.  This program is complemented by an active research program that is focused on the host response to pathogens in the lung.  Please also see our program in Acute Lung Injury and Lung Immunology

 Proteostasis

Proteostasis is the dynamic process by which cells control the concentration, conformation, binding interactions, and location of individual proteins making up the proteome through a system of regulated networks of interacting and competing biological pathways that influence protein synthesis, folding, trafficking, disaggregation, and degradation.  In C. elegans, a systemically coordinated genetic program is activated upon fecundity that results in a progressive decline in the function of the proteostasis network.  Genetically interrupting this process results in a prolonged lifespan with enhanced stress resilience.  We are using combined approaches including imaging, transcriptomics, proteomics and epigenomics to define the function of the proteostasis network in the lung with age in comparison with other organ systems and to identify factors that might enhance proteostasis over the lifespan.

 Pulmonary Fibrosis

Pulmonary fibrosis is a devastating disorder in which delicate alveolar tissue is progressively replaced by collagen and other matrix proteins.  This results in a fall in lung compliance, increasing the work of breathing and threatening gas exchange.  Intensive research have identified a handful of therapies that slow the progression of disease, but curative therapies remain elusive.  Our group studies several aspects of fibrosis, including the role of alveolar macrophages in the development of disease, the role of the Wnt/β-catenin pathway in the development of fibrosis and potential metabolic controllers of fibrosis We collaborate closely with our colleagues in Rheumatology in the study of scleroderma induced ILD, particularly Harris Perlman, PhD.  Our group is closely integrated with our clinical ILD group and our active lung transplantation program.

 Systemic Effects of Lung Injury

In patients with ARDS, skeletal muscle dysfunction develops rapidly and may contribute to weaning failure, prolonged mechanical ventilation and the risk of readmission after ICU discharge and mortality.  In addition, limb muscle dysfunction is observed in the majority of survivors of ARDS and may persist for as long as 5 years after discharge, where it is a major driver of morbidity.  Our group seeks to understand how lung injury drives muscle dysfunction.