Dr. Toews' Laboratory


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Research Goals
Funding
Techniques used in the laboratory
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Lab phone:  402-559-7197


Research Goals

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


Collaborators

Debra Romberger, MD, Department of Internal Medicine, UNMC
Stephen Rennard, MD, Department of Internal Medicine, UNMC
Keshore Bidasee, PhD,  Department of Pharmacology and Experimental Neuroscience, UNMC
Yaping Tu, PhD, Creighton University School of Medicine


Funding

Oxytocin ligand/receptor variants and social behavior
PI: M. Toews
Source: University of Nebraska, Omaha

Techniques used in the laboratory


Personnel

Michael Douchey
Student Worker
Michael Douchey
Aaryn Mustoe
Research Associate
Aaron Mustoe
Nancy Schulte
Researcher
nancyshulte

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