The underlying research interest of our lab, is the molecular pathology of G Protein-Coupled Receptors and our entry point into these fields begins with the development of novel antibodies. These unique reagents help define the underlying biological mechanisms in pathology, the diagnostic expression patterns, and in some cases, the potential for therapeutic intervention. In two projects the momentum of these studies in basic science is shifting towards translational research and clinical trials. More specifically, anti-human calcitonin receptor antibodies have been developed, which are first-in-class worldwide, against extracellular and intracellular epitopes.
Projects An anti-calcitonin receptor (CTR) antibody for the detection of programmed cell death: the role of CTR in a novel adaptive response in a pre-apoptotic mechanism
Programmed cell death (PCD) is an essential process in life. The sequelae of events resulting in PCD, include changes in mitochondrial membrane potential, shunting of phosphatidylserine to the cell surface, activation of caspases, chromatin condensation and DNA fragmentation, amongst other key molecular events. Less well established in cells under duress from cytotoxins is an adaptive response which includes increasing metabolism and concomitant expression of CTR. A conjugate of the anti-CTR antibody (AlexaFluor 568) is able to detect PCD in vitro
and further studies are aimed at defining its potential for imaging PCD in vivo
The efficacy of an anti-calcitonin receptor (CTR) antibody conjugated to toxin to reduce tumour expansion in mouse xenograft models of brain tumour.
Monoclonal antibodies that target the extracellular epitope have been conjugated to toxins to selectively kill brain tumour stem cells with EC50s in the 4-10pM range in vitro
. Studies are now underway to study efficacy in