Skip to main content

The upper airways serve to clean inspired air from physical, chemical and pathological detritus that might damage the delicate peripheral airways where oxygen exchange is achieved. It is the heart of a powerful two tiered  innate immune system based upon a  layer of mucus that captures the incoming material that is moved over a bed of cilia. The system is called the muco-ciliary escalator.
Failure of this complex protective system is associated with a wide variety of diseases such as cancer and chronic inflammatory diseases. Biomolecules in mucus are split into two distinct groups, the first group being of globular type proteins between 6 kDa to 200 kDa and the second being of mucins which are large, space-filling glycoconjugates of 200 kDa to 100 MDa, with most of this mass being of carbohydrate in origin. Besides these biomolecules, mucus also contains secreted vesicles (exosomes) with innate immune properties. In chronic inflammatory lung diseases like cystic fibrosis (CF), chronic bronchitis (COPD) and asthma, mucus quantity and quality is altered and it is not efficiently removed from the lungs, causing airway obstruction, impaired gas exchange, bacterial colonization & infection and damage to lung tissue. The long term goal of our laboratory is to understand how this innate immune barrier is dynamically organized around the protective macromolecules under normal and pathological conditions. Currently, research in the Kesimer laboratory is focused on three main fundamentally important areas: 1- How mucins and globular proteins are organized within the airway mucosal barrier and how they are altered in disease pathogenesis, 2- How mucins are processed to mature after granular release for optimal function and how this progression is altered in chronic lung diseases, CF in particular, and 3- The role of extracellular vesicles in the airway mucosal barrier. Our laboratory is established with a wide range of state of the art biochemical, biophysical and proteomics methods including UPLC-Orbitrap mass spectrometry, atomic force microscopy, dynamic and static light scattering, and a variety of surface biophysics tools including QCM-D.,The upper airways serve to clean inspired air from physical, chemical and pathological detritus that might damage the delicate peripheral airways where oxygen exchange is achieved. It is the heart of a powerful two tiered  innate immune system based upon a  layer of mucus that captures the incoming material that is moved over a bed of cilia. The system is called the muco-ciliary escalator.
Failure of this complex protective system is associated with a wide variety of diseases such as cancer and chronic inflammatory diseases. Biomolecules in mucus are split into two distinct groups, the first group being of globular type proteins between 6 kDa to 200 kDa and the second being of mucins which are large, space-filling glycoconjugates of 200 kDa to 100 MDa, with most of this mass being of carbohydrate in origin. Besides these biomolecules, mucus also contains secreted vesicles (exosomes) with innate immune properties. In chronic inflammatory lung diseases like cystic fibrosis (CF), chronic bronchitis (COPD) and asthma, mucus quantity and quality is altered and it is not efficiently removed from the lungs, causing airway obstruction, impaired gas exchange, bacterial colonization & infection and damage to lung tissue. The long term goal of our laboratory is to understand how this innate immune barrier is dynamically organized around the protective macromolecules under normal and pathological conditions. Currently, research in the Kesimer laboratory is focused on three main fundamentally important areas: 1- How mucins and globular proteins are organized within the airway mucosal barrier and how they are altered in disease pathogenesis, 2- How mucins are processed to mature after granular release for optimal function and how this progression is altered in chronic lung diseases, CF in particular, and 3- The role of extracellular vesicles in the airway mucosal barrier. Our laboratory is established with a wide range of state of the art biochemical, biophysical and proteomics methods including UPLC-Orbitrap mass spectrometry, atomic force microscopy, dynamic and static light scattering, and a variety of surface biophysics tools including QCM-D.


UNC AFFILIATIONS:

Marsico Lung Institute, Pathology & Lab Medicine

CLINICAL/RESEARCH INTERESTS:

Biochemistry, Cell Biology, Molecular Biology, Pathology, Translational Medicine

Leave a Reply