Kevin Frankowski, Ph.D.
Assistant Professor, Center for Integrative Chemical Biology and Drug Discovery
3212 Marsico Hall, 125 Mason Farm Road, CB# 7363, Chapel Hill, NC, 27599
A central tenet of our research is the development of small molecule tools to better understand neurotransmitter signaling. Our current efforts focus on programs for the kappa opioid, dopamine and sigma receptors. Each is a highly collaborative effort in concert with screening facilities and pharmacology experts, which has led to the identification of selective modulators for the individual receptors or receptor subtypes. Of particular interest toward our overarching goal is the recent revelation that CNS receptors are capable of biased activation (i.e. preference for either the G protein or βarrestin pathways). We have discovered G protein biased ligands for the kappa opioid receptor and have ongoing efforts to identify promising biased ligands for dopamine receptors. These biased ligands serve as molecular tools to study the mechanistic details, behavioral effects and therapeutic potential of biased activation. A related area of high interest is the identification of allosteric modulators, with our efforts on this front focused on individual dopamine receptor subtypes. Overall, the identification and characterization of selective molecular tools will greatly aid the investigation into the nuanced regulation and interconnectivity of neurotransmitter signaling.
Other research efforts are aimed at developing new approaches for the treatment of unmet medical needs. For example, while much progress has been made targeting primary tumor sites certain types of cancer still present disproportionately high mortality rates. Pancreatic cancer has a mortality rate of over 90%, almost exclusively through metastasis of the primary tumor. We have discovered an effective antimetastatic agent that reduces the prevalence of the perinucleoar compartment, a phenotypic indicator of metastatic potential. The compound has demonstrated in vivo efficacy in preventing or reducing the metastatic transformation of tumor grafts. Current efforts are directed toward advancing the promising therapeutic potential and elucidating the mechanism of action for this class of compounds.