Grant: Travel Awards - Institute Community Support

Smooth muscle plays an important role in the regulation of vascular tone as well as a myriad of other biological functions. Central to this proposal, tone management is a key contribution of the vascular smooth muscle (VSM) tissue, which when functioning normally, contributes to general health and wellness but when dysfunctional is associated with morbidity and mortality. For example, an increase in VSM contractility is known to contribute to the severe arterial narrowing observed in cerebral and coronary vasospasm, in chronic hypertension and in the decreased dilatory responses of arteries in obesity, diabetes and aging. The fine control of VSM tone is essential for maintenance of normal cardiovascular function. The biochemical systems that govern VSM are complex, yet zipper-interacting protein kinase (ZIPK) has emerged as one of the most important factors that regulate this mechanism. Indeed, research suggests that ZIPK can promote VSM contractility in health and disease. More recent studies suggest that there is a strong correlation between ZIPK and cancer development and progresion. Taken togther, I will investigate the role of ZIPK in cardiovascular diseases and cancer . During the timeline of this proposal, I propose to address a number of knowledge limitations and develop important tools to better interrogate the physiological function(s) of ZIPK. These investigations will reveal the potential for development of inhibitors of ZIPK for attenuation of its cellular activity. Accordingly, the validation of specific inhibitors (or activators) of ZIPK would be particularly advantageous, not only in promoting our basic understanding of this signalling module but also for clinical application for treatment of contractile disorders. Furthermore, the knowledge that will be gained by my investigations will enable exploration of additional functions of this critically important kinase in cancer disease.