John Cavanagh, Ph.D.

Recently, researchers in the program have discovered a synthetically accessible class of molecules that appear to increase the effects of novel anticancer drugs by several orders of magnitude.  The overarching goal is to reduce the working concentrations of ALL anti-cancer drugs in order to mitigate serious side effects.  Here, we propose to develop and screen our new molecules with both novel and existing chemotherapeutics against a variety of cancer cell lines in order to define the optimum combination treatment. 
 
Also we are working on tumor formation. 
 
The life and death of cells must be balanced if tissue homeostasis is to be maintained-there should neither be too much growth nor too little death.  Normal cells accommodate this balance by invoking intrinsic programmed cell death, referred to as apoptosis.  Apoptosis is triggered via three signaling pathways.  If apoptosis does not occur correctly and cells do not die, then malignant tumors form.  It is no surprise therefore that countless cancer therapeutics are being developed to control apoptosis. 
 
It is known that all three apoptosis signaling pathways route through a protein known as caspase-3.  If caspase-3 fails to function, then cell death does not happen correctly and cancer occurs.  It is known that a calcium-binding protein known as calbindin-D28K binds to caspase-3 and stops it functioning.  If we can stop calbindin-D28K from interfering with caspase-3, apoptosis would occur normally and the risk of cancer developing would be significantly reduced.  Consequently calbindin-D28K is a particularly powerful target for anticancer drug development.