Research in the Evans-Molina Lab has shown that β cell function and survival is strongly governed by ER and Golgi health, which is dependent on intact ER and Golgi calcium compartmentalization and the maintenance of a steep calcium gradient between these organelles and the cytosol. Work in the Evans-Molina Lab has identified and characterized several molecular pathways leading to loss of ER calcium homeostasis in diabetes. To date, these studies have focused on a role for impaired ER calcium uptake via dysregulated expression and activity of the sarco-endoplasmic reticulum calcium ATPase 2b (SERCA2b) pump.
Additional projects focus on understanding the impact of impaired store-operated calcium entry, arising from decreased expression of the ER calcium sensor, STIM1. In a collaborative project with Dr. Jim Johnson at the University of British Columbia and Dr. Marjan Slak Rupnik at the University of Vienna, the lab is working to investigate how ryanodine receptor dysfunction impacts β cell function and survival.
More recently, the lab has initiated studies to define β cell Golgi stress in diabetes and investigating how loss of function of the secretory pathway calcium ATPase (SPCA1) in the Golgi impacts insulin secretion and autophagy.
The lab maintains a strong translational focus and has initiated a recent collaboration with Dr. Decio Eizirik at the Universite Libre de Bruxells and Dr. Russell Dahl and Colleen Mauger at Neurodon to develop and test novel allosteric SERCA activators in models of diabetes. The lab also has an active collaboration with Dr. Jakob Wikstrom at the Karolinksa Institute focused on understanding the metabolic phenotypes of individuals with Darier-White and Hailey-Hailey Disease, rare disorders resulting from haploinsufficiency of SERCA2 or SPCA1.