Welcome to Dr. Myron Toews Laboratory
Dr. Deb Romberger
Dr. James Turpen
Current studies in my laboratory are focused on extracellular mediators and their receptors and signaling pathways in relation to lung diseases other than lung cancer, mainly diseases of the "airways" such as asthma, pulmonary fibrosis and chronic bronchitis.
One focus is on the roles of the simple lipid mediator lysophosphatidic acid (LPA) in airway disease. LPA is known to be released at sites of tissue injury and to mediate wound repair, for example when we cut our finger. Many diseases of the lung, including asthma, chronic bronchitis, and pulmonary fibrosis, are thought to result from repeated lung injury followed by inappropriate repair responses that lead to an altered structure of the lung tissue. We published many studies showing disease-relevant effects of LPA on lung cells. Recent studies from other groups have now confirmed the importance of LPA in airway disease using knockout mice. We continue to work on this project, with a major focus the sources of this LPA and on identifying the specific LPA receptors and signaling pathways involved in these airway diseases. The long-term goal is to identify drugs that alter the production, destruction, or actions of LPA to treat these lung diseases.
Another focus is on the cellular and molecular mechanisms involved in development of obstructive lung disease in agricultural workers exposed to animal barn dusts, especially hogbarn dust. Our recent studies have shown that an extract of this hogbarn dust both activates and then down-regulates receptors for epidermal growth factor (EGF receptors) on airway epithelial cells. LPA shares these effects with the hogbarn dust, and our prior studies of LPA regulation of EGF receptors is guiding our studies of the hogbarn dust effects. We are also working to identify the specific factors in the dust that mediate the disease-relevant effects on airway epithelial cells, which may allow us to develop new and more specific therapies.
Adrenergic receptor signaling and regulation have been long-term interests in my laboratory, and another current focus is on signaling pathways by which these receptors regulate cell growth. Patients with asthma have excess airway smooth muscle cell growth, which makes their disease worse. Beta-2 adrenergic receptor agonists, which are used to "open up" asthmatic airways, can also reduce airway smooth muscle cell growth. Our recent studies show that these effects are mediated through cyclic AMP activation of the protein EPAC (Exchange Protein Activated by CyclicAMP) rather than through the more traditional cyclic AMP target protein kinase A. We are further characterizing this novel growth-inhibiting pathway as a target for new asthma therapies.
Short Course: Integrative and Organ Systems Pharmacology
PI: Myron Toews
The purpose of this two-week short course is to provide graduate students, postdocs, junior faculty and industrial scientists with lectures, demonstrations and hands on experiences with relative to pharmacological investigations in isolated organ systems and intact animals.
Modulation of Inflammation-Related miRNAs by Fluticasone and Salmeterol in Lung Cells
PI: Myron Toews
The goal of this project is to determine the effects of the two asthma drugs salmeterol and fluticasone, alone and in combination, on the expression of two inflammation-regulating miRNAs, specifically miR-155 and miR-146a, on airway cells grown in culture.
Targeting Airway Inflammation from Concentrated Animal Feeding Operation Dust
PI: Deb Romberger
Co-I: Myron Toews
This project investigates the cellular and molecular basis for the airways disease that occurs in swine confinement facility workers. The major goals of Dr. Toews's part of this project are to identify the chemical/biochemical nature of the factor(s) present in an extract of hog dust that mediates disease-relevant effects such as IL-6 and IL-8 secretion, with an emphasis on the possible role of lysophosphatidic acid as a hog dust factor or mediator.
Modulation of Airway Muscle LPA Receptors and Signaling by Salmeterol and Fluticasone
PI: Myron Toews
Lysophosphatidic acid (LPA) is a lipid mediator whose effects are mediated by specific receptors. Both LPA and its receptors have not been strongly tied to asthma and to fibrotic lung disease. This project examines whether the two Glaxo drugs that are widely used to treat asthma and COPD, fluticasone and salmeterol, have regulatory effects on the number of receptors for LPA or on the ability of LPA to modulate cellular responses relevant to these diseases. The studies are conducted with isolated human airway smooth muscle cells in culture, since these cells are the primary target for these drugs, at least in the case of asthma.
Nebraska Research Network in Functional Genomics
PI: James Turpen
This grant focuses on infrastructure and research internships for undergraduate institutions in the state of Nebraska. Dr Toews is in charge of about 10 research projects being conducted by faculty at these smaller teaching-oriented institutions, supervising their interactions with individual mentors and helping to promote their development of a viable research atmosphere for promoting careers in biomedical research for their students.