The University of Texas Medical School at Houston
gray bar graphic
  UTHSC-H     People Directory     Webmail     Calendar      A-Z
Search
BMB Home | Meet the Faculty | BMB Newsletter | BMB Links | Contact BMB
 
 
About BMB

About BMB

Meet the BMB Faculty Members

Dr. Michael Blackburn, Professor, Program Director

Dr. Michael BlackburnDepartment of Biochemistry and Molecular Biology
Program in Biochemistry and Molecular Biology

University of Texas-Houston Medical School
P.O. Box 20708 - Houston, Texas 77225
(713) 500-6087: fax (713) 500-0652
email: Michael.R.Blackburn@uth.tmc.edu

Ph.D., Thomas Jefferson University
NIH Postdoctoral Fellow, Baylor College of Medicine

Junior Investigator Award, Sandler Program for Asthma Research

Career Investigator Award, American Lung Association

Molecular Models of Adenosine Signaling

and Chronic Lung Disease

Inflammatory and remodeling responses are prominent features of chronic lung diseases such as asthma, chronic obstructive pulmonary disease (COPD), and pulmonary fibrosis. In contrast to most injury and repair responses, the inflammation and remodeling seen in these diseases may last throughout the life of the afflicted individual. Although signaling pathways associated with the genesis of inflammation and the control of tissue remodeling have been described, little is known about signaling pathways that serve to regulate the chronic nature of these diseases. The major goal of my laboratory is to identify pathways that regulate the chronicity of asthma, COPD and pulmonary fibrosis with the intent of developing novel therapeutic strategies.

A central hypothesis of my laboratory is that the signaling nucleoside adenosine is an amplifier of lung inflammation and damage. Adenosine is generated in response to cell stress or damage and is therefore a byproduct of the inflammation and damage set up by any number of initiators of lung inflammation. It is our belief that as adenosine levels increase in the lung they access pathways that serve to promote airway inflammation and remodeling. Adenosine signals by engaging specific adenosine receptors on target cells such as mast cells, lymphocytes, eosinophils, macrophages, airway epithelial cells and smooth muscle cells. Most of the projects in my laboratory focus on understanding the mechanisms by which adenosine receptor signaling influences the activities of these cells in the context of lung inflammation and remodeling.

We make extensive use of genetically modified mice to examine the role of adenosine signaling in chronic lung disease. This includes knockout mice deficient in enzymes of adenosine metabolism and knockout mice deficient in the various adenosine receptors. In addition, we utilize transgenic mice that over express components of adenosine signaling specifically in the lung. With these genetic tools we can assess the contribution of specific aspects of adenosine signaling in chronic lung diseases in the context of the whole animal.

Figure 1

Model of adenosine-mediated amplification of chronic lung disease

Multiple factors contribute to the generation of chronic lung diseases such as asthma and COPD. The ensuing inflammation and damage that occurs in these conditions leads to the catabolism of ATP to adenosine. Adenosine then interacts with various adenosine receptors on the surface of target cells to increase the production of mediators that drive chronic airway inflammation and remodeling.

 
Selected References

Mohsenin, A., Burdick, M. D., Molina, J. G., Keane, M. P. and Blackburn, M. R. (2007) Adenosine mediated CXCL1 production and angiogenesis in the lungs of adenosine deaminase deficient mice.  FASEB J. 21, 1026-1036.

Chunn, J. L., Mohsenin, A., Young, H. W. J., Lee, C. G., Elias, J. A., Kellems, R. E. and Blackburn, M. R. (2006) Partially adenosine deaminase-deficient mice develop pulmonary fibrosis in association with adenosine elevations. Am. J. Phys. Lung Cell Mol. Physiol. 290, 579-587.

Volmer, J. B., Thompson, L. F. and Blackburn, M. R. (2006) A protective role for ecto-5’-nucleotidase (CD73) in bleomycin-induced pulmonary fibrosis.  J. Immunol. 176, 4449-4458.

Young, H. W. J., Sun, C.-X., Evans, C. M., Jacobson, M. A., Dickey, B. and Blackburn, M. R. (2006) A3 adenosine receptor signaling contributes to airway mucin secretion following allergen challenge. Am. J. Respir. Cell Mol. Biol. 35, 549-558.  

Sun, C. X., Zhong, H., Mohsenin, A., Morschl, E., Chunn, J. L., Molina, J. G., Belardinelli, L., Zeng, D. and Blackburn, M. R. (2006) Role of A2B adenosine receptor signaling in adenosine-dependent pulmonary inflammation and injury in adenosine deaminase deficient mice. J. Clin. Invest. 116, 2173-2182.

Sun, C.-X., Young, H. W., Molina, J. G., Volmer, J. B., Schnermann, J. and Blackburn, M. R. (2005) A protective role for the A1 adenosine receptor in adenosine-dependent pulmonary injury.  J. Clin. Invest. 115, 35-43.

Chunn, J. L., Molina, J. G., Mi, T., Xia, Y., Kellems, R. E. and Blackburn, M. R. (2005) Adenosine-dependent pulmonary fibrosis in adenosine deaminase-deficient mice. J. Immunol. 175, 1937-1946.

Young, H. W. J., Molina, J. G., Dimina, D., Zhong, H., Jacobson, M., Chan, L.-N. L., Chan, T. S., Lee, J. J. and Blackburn , M. R. (2004) A3 adenosine receptor signaling contributes to airway inflammation and mucus production in adenosine deaminase-deficient mice. J. Immunol. 173, 1380-1389.

Banerjee, S. K., Young, H. W. J., Barczak, A., Earle, D. and Blackburn , M. R. (2004) Abnormal alveolar development associated with elevated adenine nucleosides. Am. J. Respir. Cell Mol. Biol. 30, 38-50.

Blackburn, M. R. , Chun, G. L., Young, H. W. J., Zhu, Z., Chunn, J. L., Kang, M. J., Banerjee, S. K., and Elias, J. A. (2003) Adenosine mediates IL-13-induced inflammation and remodeling in the lung and interacts in an IL-13-adenoisne amplification pathway. J. Clin. Invest. 112, 332-344.

Zhong, H., Sergiy, S., Molina, J. G., Sanborn, B. M., Jacobson, M. A., Tilley, S. L. and Blackburn, M. R. (2003) Activation of murine lung mast cells by the adenosine A 3 receptor. J. Immunol . 170, 338-345.

Banerjee, S. K., Young, H. W. J., Volmer, J. B. and Blackburn , M. R. (2002) Gene expression profiling in inflammatory airway disease associated with elevated adenosine. Am. J. Phys. Lung Cell Mol. Physiol., 282, L169-L182.

Chunn, J. L., Young, H. W. J., Zhong, H., Banerjee, S. K., Colasurdo, G. N. and Blackburn, M. R. (2001) Adenosine-dependent airway inflammation and hyperresponsiveness in partially adenosine deaminase deficient mice. J. Immunol., 167, 4676-4685.

Blackburn , M. R. , Volmer, J. B., Thrasher. J. C., Crosby, J. R., Lee, J. J. and Kellems, R. E. (2000) Metabolic consequences of adenosine deaminase deficiency in mice are associated with defects in alveogenesis, pulmonary inflammation and airway obstruction . J. Exp. Med ., 192, 159-170.

Search PubMed for a complete list of Dr. Blackburn's publications.