Gregory E. Conners, Ph.D.
Associate Professor of Cell Biology & Anatomy and Medicine

Research Programs & Locations

This research program is divided into two components: 1) a basic cell biology component that focuses on intracellular trafficking of proteins in the secretory pathway especially as it relates to the mechanisms of lysosome biogenesis; and 2) a more clinically relevant component on pulmonary cell biology with a main focus on the function and composition of secretions in normal and diseased airways.

These research areas provide opportunities for graduate fellows with diverse interests to develop their own thesis research programs. A variety of techniques are available for use on thesis projects including recombinant DNA/molecular biology, immunochemistry, various types of microscopy, cell culture, and subcellular fractionation.

SELECTED PUBLICATIONS

• Casalino-Matsuda SM, Monzon ME, Conner GE, Salathe M, Forteza RM. Role of hyaluronan and reactive oxygen species in tissue kallikrein-mediated EGF receptor activation in human airways. J Biol Chem. 2004 Feb 26 [Epub ahead of print]
  
• Campos MA, Abreu AR, Nlend MC, Cobas MA, Conner GE, Whitney PL. Purification and characterization of PLUNC from human tracheobronchial secretions. Am J Respir Cell Mol Biol. 2004;30:184-92
  
• Horvath G, Sutto Z, Torbati A, Conner GE, Salathe M, Wanner A. Norepinephrine Transport by the Extraneuronal Monoamine Transporter in Human Bronchial Arterial Smooth Muscle Cells. Am J Physiol Lung Cell Mol Physiol. 2003;285:L829-37
  
• Wijkstrom-Frei C, El-Chemaly S, Ali-Rachedi R, Gerson C, Cobas MA, Forteza R, Salathe M, Conner GE. Lactoperoxidase and Human Airway Host Defense. Am J Respir Cell Mol Biol. 2003;29(2):206-12
  
• Salathe M, Forteza R, Conner GE. Post-secretory fate of host defence components in mucus. Novartis Found Symp. 2002;248:20-6; discussion 27-37, 277-82.
  
• Conner GE, Salathe M, Forteza R. Lactoperoxidase and hydrogen peroxide metabolism in the airway. Am J Respir Crit Care Med. 2002;166:S57-61.
  
• El-Chemaly S, Salathe M, Baier S, Conner GE, Forteza R. Hydrogen peroxide-scavenging properties of normal human airway secretions. Am J Respir Crit Care Med. 2003;167:425-30. Epub 2002 Nov 15.
  
• Horvath G, Torbati A, Conner GE, Salathe M, Wanner A. Systemic ovalbumin sensitization downregulates norepinephrine uptake by rabbit aortic smooth muscle cells. Am J Respir Cell Mol Biol. 2002;27:746-51.
  
• Nlend MC, Bookman RJ, Conner GE, Salathe M. Regulator of G-protein signaling protein 2 modulates purinergic calcium and ciliary beat frequency responses in airway epithelia. Am J Respir Cell Mol Biol. 2002;27:436-45.
  
• Horvath G, Lieb T, Conner GE, Salathe M, Wanner A. Steroid sensitivity of norepinephrine uptake by human bronchial arterial and rabbit aortic smooth muscle cells. Am J Respir Cell Mol Biol. 2001;25:500-6.
  
• Forteza R, Lieb T, Aoki T, Savani RC, Conner GE, Salathe M. Hyaluronan serves a novel role in airway mucosal host defense. FASEB J. 2001; 15: 2179-86.
  
• Horvath G, Lieb T, Conner GE, Salathe M, Wanner A. Steroid sensitivity of norepinephrine uptake by human bronchial arterial and rabbit aortic smooth muscle cells. Am J Respir Cell Mol Biol. 2001; 25: 500-6.

 AIRWAY CELL BIOLOGY

Protection of the Respiratory System Secreted Enzymes of the Airway Mucosa

The airway mucosa represents one of the most important interfaces between an animal and its environment. The mucosa must provide a sophisticated defense against airborne material of a variety of sizes and composition. Unsuccessful or inappropriate response of the airway mucosa is detrimental to the airway and underlying tissues.  Over the last four years, we have developed a program in pulmonary cell biology that  is a new and important focus of our research efforts.  The program studies components of airway secretions that may play a role in respiratory diseases.

Hydrogen peroxide has been shown by others to be elevated during airway inflammatory diseases such as asthma and is a major contributor to the inflammatory reactions associated with a variety of airway diseases.  Our studies have identified the major hydrogen peroxide scavenging activity in airway secretions. We have now purified and characterized the activity and shown it to be a single protein that comprises 1 percent of the soluble secreted protein in sheep airways. Enzymatic and spectral analysis show that the peroxidase is very similar to lactoperoxidase expressed in the mammary gland. This airway peroxidase is secreted by goblet cells and may function both in a biocidal capacity and in controlling the reactive oxygen species in the airway.  Other biochemically similar peroxidases produce biocidal compounds to protect against infection. We hypothesize that airway peroxidase has a similar function in the sheep respiratory tract.  Current studies focus on testing this hypothesis and further characterization of the protein by amino acid sequencing and cDNA cloning of  this peroxidase.

Human airway secretions also contain peroxidase. We are studying levels of  airway peroxidase and substrates in secretions of cystic fibrosis patients who have frequent bacterial infections and defects in ion transport that may also alter peroxidase substrate concentrations.  We are also studying peroxidase in asthmatics who typically  have elevated levels of hydrogen peroxide during periods of heightened inflammation.  In addition,  we are examining the regulation of the peroxidase system in cultures of differentiated airway epithelial cells.

Tissue kallikrein is also secreted into the airway primarily by serous cells of the submucosal glands. This enzyme cleaves polypeptide hormones and precursors into active forms. Bronchial tissue kallikrein mediates bronchoconstriction in response to a variety of stimuli by cleaving high molecular weight kininogen to form lysyl-bradykinin that in turn causes bronchial smooth muscle contraction. Bronchial kallikrein is believed to mediate aspects of airway hyper responsiveness and inflammation, and thus is thought to play a role in asthma. This enzyme is currently being purified and characterized in order to better understand how it is regulated in normal and inflamed airways.

LABORATORY MEMBERS AND COLLABORATORS

William M. Abraham, Ph.D., Affiliated Professor of Medicine and Director of Research, Mt. Sinai Medical Center; Rosanna Forteza, M.D., Assistant Professor of Medicine, University of Miami School of Medicine; Matthias Salathe, M.D., Associate Professor of Medicine, University of Miami School of Medicine; Aliza Torbati, B.S., Affiliated Research Associate. Miryam Fragosa, Graduate Student; Radia Al-Rachedi, Graduate Student. Adam Wanner, M.D., Professor and Chief, Pulmonary Division.

CONTACT INFORMATION