Job Description

Diabetes is the world's fastest-growing disease with high morbidity and mortality rates. Our recent work identified a set of allosteric modulators of the SERCA enzyme - generating drugs targeting diseases such as diabetes associated with ER stress related pathways. These agents increase the Vmax of SERCA2b, increase Ca2+ content of the ER, effectively reduce the ER stress response, enhance glucose tolerance, and reduce hepatosteatosis. Using modeling approach and Medicinal chemistry we aim at expanding our SERCA-small molecule program by identifying and generating new classes of SERCA agonists which are selective and more potent and efficient in activating SERCA. Structure-based binding site identification and Ligand-based virtual screening are underway.

Description of activities
A- 1) test the biological activities of newly identified compounds in cell-based assays such as Ca2+-ATPase and ER stress assays; 2) Design mutants that will prevent CDN1163 compounds from fitting into putative binding pockets. These mutants will be used for experimental validation of the putative pockets; 3) test Med Chem optimized scaffolds. 4) test the most promising hits in vivo in diabetes models (glucose levels, insulin levels, ER stress, signal transduction mechanisms, calcium homeostasis and signaling, mitochondrial signaling and apoptosis.
B- Participate participate in and may lead other active projects in the lab when appropriate, in addition to writing and reviewing manuscripts.
C- Will be trained to perform some essential laboratory skills such as cardiomyocytes isolation (adult + neonatal), cardiomyocyte mechanics (Ionoptix) and potentially Echocardiography when possible.
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