In a new issue of Journal of Clinical Investigation, Senior Investigator Denisa Wagner, Ph.D., and colleagues have shed light on the regulatory powers of a molecule called CalDAG-GEFI, which according to Wagner exists as a kind of "red light at the intersection" of multiple biological pathways.

The paper, online as of May 2007 before print publication, explains CalDAG-GEFI's role as a regulator of thrombosis, inflammation, and most likely immunity. Specifically, Wagner and fellow scientists found that mice without the molecule exhibited a syndrome of combined defects in platelet and immune cell function, most prominently elevated levels of neutrophils that are defective in migrating to sites of inflammation. The mice evidenced a condition very similar, in fact, to patients with leukocyte adhesion deficiency (LAD) syndrome. Hence, a potential treatment for LAD could be gene therapy that turns on the gene producing CalDAG-GEFI.

First author on the JCI paper was Junior Investigator Wolfgang Bergmeier, Ph.D., who is leaving the Wagner lab this summer to establish his own lab at Jefferson Medical College in Philadelphia. Other IDI scientists collaborating on the paper are Tobias George, Stephen Cifuni, and Andrew Baldwin (student intern), joined by scientists from the Center for Cancer Research and the McGovern Institute for Brain Research, both at MIT.

According to Bergmeier, this discovery about CalDAG-GEFI may have "a huge impact for our understanding of thrombosis and inflammation, with lots of medical implications." For example, finding means to inhibit the molecule could lead to therapies for diseases such as sepsis or for the thrombotic complications that plague cancer patients. Bergmeier is currently researching the basic signaling processes of CalDAG-GEFI within cells.