[LCMI Roster]

The Lung Cellular, Molecular, and Immunobiology [LCMI] Study Section reviews grant applications designed to study the genetic, molecular, and cellular basis of normal respiratory biology, and development, and the alterations in these processes in inflammatory and immune lung disorders.   The study section will consider applications using molecules, cells, tissues, organs, animal models, and/or human investigations that address the identity, function, and products of the cells that populate the upper and lower airways and alveolar regions, the regulation and dysregulation of innate host defense mechanisms and the adaptive immune system in health and disease as they relate to the respiratory system.  Topics may include the inflammatory and immune mechanisms that contribute to the pathogenesis of a variety of airway and alveolar diseases of the lung, including, but not limited to, asthma, Chronic Obstructive Pulmonary Disease, and cystic fibrosis.

Specific areas covered by LCMI:

• Cellular and molecular mechanisms in the normal lung.  This includes examinations of lung cell biology in relationship to localization, phenotype expression, secretory products, and effector profile of cells in the lung.  Examples of appropriate cells include airway epithelium, alveolar epithelium, airway smooth muscle, dendritic cells, fibroblasts, myofibroblasts, other mesenchymal cells, alveolar macrophages, leukocytes, mast cells, basophils, and goblet cells and glands.
  
  
• Basic cellular and molecular mechanisms involved in respiratory system development and pattern formation including topics such as genetic control, growth factors, and signaling mechanisms.
  
  
• Genetics and gene expression studies in normal and inflamed lung, including gene identification, expression, function, genotype-phenotype relationships, and gene- environment interactions.
  
  
• Regulation and dysfunction of adaptive/acquired, humoral and mucosal immunity in the normal and diseased lung.
  
  
• Regulation and dysfunction of innate immunity/host defense in the normal and diseased lung.  Examples include airway antimicrobials, mucociliary clearance, macrophage, dendritic cells, mucins, surfactant, toll and other pattern-recognition receptor biology.
  
  
• Lung and airway immune responses to infectious agents (e.g., virus, bacteria, and fungus) that can contribute to the pathogenesis, progression or exacerbation of asthma, COPD, and Cystic Fibrosis.
  
  
• The pathogenesis and consequences of different types of pulmonary inflammation.  Examples include the roles of mediators, cytokines, and gaseous molecules and their receptors/targets in disease processes and mechanisms of cell trafficking, including cell adhesion, chemotaxis, and cell migration and interactions between airway nervous system and immune cells and their products.
  
  
• Mechanisms of asthma pathogenesis, including immune and inflammatory mechanisms, mucosal immunity, airway hyper-responsiveness, pulmonary responses to allergens, role of innate immunity, biology of inflammation, and the biology of pulmonary infections.
  
  
• Mechanisms of COPD pathogenesis, including study of inflammation, mucus metaplasia, cytokine and mediator networks, leukocyte biology, contributions of infection, alterations in the innate and adaptive immune responses, protease - antiprotease balance, contributions of apoptosis, altered secretory processes, altered epithelial permeability and function, and angiogenesis.
  
  
• Mechanisms of the pathogenesis of Cystic Fibrosis in the lung, including genetics, modifier genes, geneotype-phenotype relationships, development, ion transport, epithelial function, mucociliary clearance, mucus biology, inflammation, infection, and innate host defense mechanisms.
  
  
• Application of lung transplantation to the therapy of pulmonary diseases.  Acute and chronic changes in respiratory system function that result from lung transplantation.
  
  
• Mechanisms of lung dysfunction in genetic disorders of lung defense, including surfactant deficiencies and ciliary disorders.
  
  
• Development of strategies for cell-based therapies in the lung, including gene therapy, cell transplantation approaches, dendritic cell modification, and modification of cytokine, mediator, and adhesion molecule systems.

LCMI has the following shared interests within the RES IRG:

• With the Lung Injury, Repair and Remodeling [LIRR] Study Section:

o        Basic mechanisms and immunobiology of asthma should be considered by LCMI, whereas occupational asthma and airway disease can be assigned to LIRR.  Studies that include repair and remodeling in asthma and COPD may be assigned according to the central interests of the application.

o        Applications that focus on the basic biology of the innate immune system in the lung would be assigned to the LCMI.  Studies addressing functions of innate immune system in the setting of infectious disease where the infection is the key issue would be assigned to LIRR.  The role of infection in asthma, COPD, or CF would also be assigned to LCMI.

o        Mediator/cytokine studies may be assigned to the three study sections in the IRG based on their disease focus.

o        There is a shared interest between LCMI and LIRR concerning fibroblasts, myofibroblasts, leukocytes, and epithelial cells.  Studies of these cells primarily focusing on lung injury, repair, and remodeling should be assigned to LIRR.  Studies of basic ontogeny and biological properties of these cells should be assigned to LCMI.

• With the Respiratory Integrative Biology and Translational Research [RIBT] Study Section:

o        Applications focusing on basic cell biology of airway smooth muscle, when normal and abnormal mechanical issues are a major focus, can be assigned to RIBT.  If immune function, proliferation, etc., of airway smooth muscle is the focus, applications can be assigned to LCMI.

o        Studies relating to cell and immune-based therapies will be assigned to LCMI if they involve modeling systems, humans or are developmental in nature.  Small-scale “proof of concept” studies in humans can also be assigned to LCMI.  Larger studies evaluating efficacy, for example, would be assigned to RIBT.

o        Studies of genetic and gene expression issues involving gene identification, expression, and function in cells, animal systems, and small human cohorts can be assigned to all three study sections in the IRG as per the disease focus.  Investigations using large cohorts with fine mapping would be assigned to RIBT.

o        Studies of basic cell biology of pulmonary vascular cells (endothelial and vascular smooth muscle cells) may be assigned to RIBT.  Pulmonary angiogenesis applications could be assigned to the LCMI if the focus is on asthma, COPD, and related disorders.  Studies of pulmonary angiogenesis in its own right would be assigned to RIBT, if lung-relevant.

o        LCMI has shared interest with both LIRR and RIBT in their consideration of lung development. The control and integrated aspects of lung development, as well as development of the pulmonary vasculature, are most appropriate for consideration by RIBT. More cellular and molecular studies (LCMI) or responses to lung injury (LIRR) would be more appropriate for assignment to these other study sections.

LCMI has the following shared interests outside the RES IRG:

• With the Biological Chemistry and Macromolecular Biophysics [BCMB] IRG:  Studies of molecules where the focus is on pulmonary function may be assigned to LCMI, whereas those developing methods or using these molecules simply as reagents may be assigned to the BCMB IRG.  In general, studies of pulmonary tissue structure and function that use primarily biophysical techniques (e.g., X-ray diffraction, electron spin resonance, and single molecular techniques) could also be assigned to the BCMB IRG.

• With the Cell Biology [CB] IRG: Studies using molecular and cellular approaches to evaluate functions specific to the pulmonary system could be assigned to LCMI.  Alternatively, studies using approaches to derive more general knowledge of cell function that use pulmonary tissue as a convenient source of material could be assigned to the CB IRG.

• With the Genes, Genomes & Genetics [GGG] IRG:  Studies focusing on genetic and genomic approaches to identification and characterization of genes involved in respiratory system function could be assigned to LCMI. If the studies propose to use genetic and genomic approaches to identify and characterize such genes but the major focus is outside of the respiratory system, then the GGG IRG could be the appropriate assignment.  Studies of quantitative genetics, genetic epidemiology and genetic analysis of complex traits, and genetically engineered animals with an emphasis on genetics rather than pulmonary biology may be assigned to the GGG IRG.

• With the Biology of Development and Aging [BDA] IRG:  Applications that focus on development (such as fundamental studies of cell cycle control, apoptosis, cell fate, or early primordial pattern formation) would be assigned to the BDA IRG.  In general, when the question being addressed is germane to the development of more than a single organ system, either because it addresses the "primordial organ" or because of the generality of the process being studied, the application would also be assigned to the BDA IRG. On the other hand, studies focused on the differentiation and development of the pulmonary system would be assigned to LCMI.

• With the Bioengineering Sciences and Technologies [BST] IRG:  Studies of the use of the respiratory system as a platform for gene delivery for non-pulmonary diseases may be assigned to the BST IRG.  Application of gene delivery technologies when it is specific for inherited and acquired lung disorders may be more appropriate for LCMI or LIRR.  Development of novel technologies may also be assigned to the BST IRG.

• With the Immunology [IMM] IRG: Applications focusing on inflammation, innate immunology, and autoimmune diseases of the lung might be assigned to LCMI.  Applications dealing with mechanisms of allergy and biologic responses to allergens insofar as they affect the lungs and respiratory tract may be assigned to LCMI.  Applications that focus on the role of the immune system in allergy and the immune system’s response to allergens may be assigned to the IMM IRG.  Lung transplant applications, where the focus is on transplant immunology, could be assigned to the IMM IRG, whereas those related to pathobiology of organ function could be assigned to LCMI.  Applications on basic, pre-clinical, and clinical investigations involving the etiology, initiation, immunopathophysiology, prevention and treatment of diseases in which the immune system plays a major role, may be assigned to the IMM IRG.

• With the Infectious Diseases and Microbiology [IDM] IRG:  Shared interest in host defense and microbial pathogenesis.  The respiratory system has several innate host defense mechanisms that protect against pathogens.  Studies of these systems, both their normal mechanisms and their dysfunction, and their interaction with microorganisms are appropriate for LCMI.  Investigations of the response to the infectious agent as it affects structure and function of the lung are also appropriate.  Studies focused on the microorganisms per se and generic host defense mechanisms may be assigned to the IDM IRG.

• With the Hematology [HEME] IRG:  Assignment of applications on the trans-differentiation of stem cells from blood stem cells to pulmonary cell types, and vice versa, would be resolved in the direction of the final phenotype.

• With the Endocrinology, Metabolism, Nutrition and Reproductive Sciences [EMNR] IRG:There is shared interest with areas related to fetal and neonatal pulmonary development, physiology and pathophysiology.  Applications that directly relate to cellular and molecular aspects of pulmonary development and function (e.g., fetal and neonatal lung cellular development and disease) could be assigned to LCMI.  Applications dealing with endocrine, metabolic, nutritional, or reproductive effects (pregnancy and fetal and neonatal well-being) on fetal and neonatal pulmonary physiology and pathophysiology could be assigned to the EMNR IRG.

• With the Surgical Sciences, Biomedical Imaging and Bioengineering [SBIB] IRG:There is significant shared interest with the SBIB IRG. Areas such as surgical interventions to treat pulmonary dysfunctions or diseases may be assigned to the SBIB IRG.  The responses of the pulmonary system to trauma, surgery, or other physiologic stress may be assigned to LCMI.