Research

Chroneos, Zissis, Ph.D.

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Contact: zissis.chroneos@uthct.edu

Education:
B.S. (Honors) Biochemistry, 1988, University of Houston
Ph.D. Biochemistry, 1992, University of South Carolina

Research Interest:
Lung surfactant.

Current Projects:

  1. Molecular and functional characterization of surfactant protein A receptors.
  2. Role of GM-CSF in Surfactant Protein A receptor regulation and function.

Lay Summary:
Lung surfactant is a specialized lipoprotein that has crucial biophysical and immunological functions in the lung. Lung surfactant coats the alveolar surface minimizing surface tension at the air-liquid interface. Without surfactant breathing would be impossible because alveoli would collapse due to the high surface tension of water. Because surfactant synthesis is activated at late stages of gestation, babies that are born premature cannot breath on their own and require enforced oxygenation and exogenous administration of surfactant until their lungs gain the capacity to produce surfactant.

Lung surfactant is not only responsible for the effortless work of breathing but it is also an integral component of the lung’s immune system. In the late 80s and late 90s, it was discovered that the surfactant proteins SP-A and SP-D can bind a multitude of pathogens that can easily access the alveolus through breathing. Since this discovery, more recent studies have shown that surfactant proteins keep the alveoli free of infection and regulate control mechanisms that help to resist active infection and to restore immune patency following infection. Understanding how these processes work at the molecular level is a critical endeavor because it helps elucidate the pathogenesis of lung infections and related syndromes such as adult respiratory distress syndrome, granulomatous diseases and asthma.

Research Overview:
The major area of interest in the laboratory is concerned with the mechanisms by which surfactant proteins control immunity in the alveolar space. One of the first steps in the removal of inhaled microorganisms involves the recognition, uptake, and destruction of microorganisms in the lysosomes of alveolar macrophages. This process is called phagocytosis and requires the expression of cell-surface receptors, which can interact with microbes directly, or indirectly through the secreted microbial binding surfactant proteins SP-A and SP-D. The projects in my laboratory aim to elucidate how surfactant protein A and its receptor SP-R210 interact and how this interaction mediates the phagocytosis and killing of microorganisms by alveolar macrophages, thereby limiting the ability of infectious organisms to cause lethal infections in the distal airway.

An overlapping area of interest is concerned with the immune properties of alveolar macrophages. Alveolar macrophages are endowed with immune properties that serve to maintain lung immunity in the specialized environment of pulmonary surfactant. The functions of alveolar macrophages are critically dependent on the autocrine and paracrine secretion of the macrophage growth factor GM-CSF. We have discovered that GM-CSF regulates the expression of the SP-R210. In light of these findings we are currently testing the hypothesis that GM-CSF regulates surfactant and immune homeostasis through the regulation of the functional activity of the SP-A receptor SP-R210.

Selected Papers and Abstracts: