In the Laboratory of Cancer and Developmental Cell Biology, we are collaborating with physicians such as Dr. Arthur Frankel  at Texas’s Scott & White Hospital and the pediatric oncologists at Spectrum Hospital in Grand Rapids, Michigan, to try to exploit the properties of anthrax lethal factor and develop a new way to fight cancers such as melanoma, as well as to provide insight into the regulation of growth and vascularization of soft-tissue cancers called sarcomas.

The effects of many disease-causing bacteria are the result of toxins they release.  The toxin released by the bacteria that cause anthrax is particularly fascinating since it is made of three different proteins; edema factor, lethal factor, and protective antigen.  On their own, each of these proteins is harmless, but combined they become deadly.  This is because edema factor and lethal factor can exert their poisonous effects only after they have been moved into cells by protective antigen.  Figuring out exactly how protective antigen does this is seen as a crucial step in developing medicines that will fight anthrax. 

Lethal factor is a protease.  This means that it is a type of protein that chops other proteins into pieces.  And not just any protein; as best we can tell, lethal factor only chops up a type of protein called a mitogen-activated protein kinase kinase, or MKK for short.

Cell and molecular biologists think MKK proteins are very interesting because they are more active in certain types of cancers, notably melanoma.  Also, MKKs promote tumor vascularization (blood vessel formation). 

MKKs also play critical roles in embryonic development.  Loss of function of some MKKs can cause defects in blood vessel formation.  Also, activating mutations in genes that regulate MKKs, as well as mutations in MKKs themselves, have been linked to pediatric syndromes such as Costello syndrome, LEOPARD syndrome, and cardio-facio-cutaneous (CFC) syndrome.