Grant: Proof of Principle Program - Phase I

We have shown that the cell surface protein, CD34, is expressed by a number of cell types that play key roles in allergic inflammation. We have also shown that deletion of the CD34 gene in mice renders them very resistant to all of the major hallmarks of asthma and a number of other inflammatory diseases. Interestingly, however, these mice do not appear to suffer from any other obvious defects in the absence of this gene. Thus, it appears that blocking the expression of this gene could potentially be therapeutic in the absence of unwanted side effects. To explore this further, we have generated mice express the human CD34 gene instead of the mouse gene and shown that these mice now regain their sensitivity to asthma. These mice now offer an ideal system for developing therapeutic strategies for interfering with human CD34 protein expression and evaluating their ability to inhibit asthma formation. We have a preliminary experiment suggesting that antibodies against human CD34 will, indeed, block asthma development in this "humanized mouse" model. The goal of this application is to further optimize this and other strategies for blocking human CD34 expression and asthma development with an eye to producing a therapeutic for future clinical trials.