Luiza Rusu
Visiting Scholar
Trainee, VBST Program
Email:
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Richard Minshall, PhD
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2023-24
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Mentors: Richard Minshall, PhD and Sarah Lutz, PhD
My research is related to Vascular Signaling and Therapeutics. My main research focus is on better understanding critical EC signaling mechanisms that promote microvascular thrombosis which can be targeted therapeutically to treat coagulopathy associated with diseases such as T2DM. I look to conduct advanced training in this area using models in which attenuation of vWF secretion can be used to prevent microvascular thrombosis and its detrimental consequences such as peripheral vascular occlusion, pulmonary embolism, and acute kidney injury in the db/db mouse model of T2DM. We will use our cell permeable 6-15 amino acid peptides based on the N-terminus of G12 that bind to αSNAP (SNAP-Binding Domain, Myr-SBD which prevent thrombin-induced vWF secretion in established in vitro and in vivo assays. These studies will assess 2 chemical families based on the library scaffolds identified by high throughput screening, as well as small molecules modified in collaboration with medicinal chemists at UICentre. Following the characterization of their direct binding capabilities by SPR, Alpha-LISA, and thermal shift assays, we will determine which molecules selectively prevent Gα12 binding to α-SNAP and inhibit vWF secretion and thrombosis in cultured human endothelial cells, in the isolated mouse lung, and in the db/db mouse model of T2DM.