Simmons Conference: Dr. Nazih Bizri, MD and Ronit “Papai” Kar

Nazih Bizri, MD 

Title: cGAS Protects Against Inflammation Associated Tumorigenesis.

Description: Our previous work has demonstrated cGAS to be protective in acute intestinal inflammation. Now we study the role of cGAS in chronic inflammation associated tumorigenesis. We show cGAS deficiency to lead to an immunosuppressive tumor microenvironment and dysfunctional intestinal epithelial autophagy. 

Mentor:  Dr. Sidrah Khan

Ronit “Papai” Kar

Title: Understanding Thrombosis and Thrombolysis Dynamics through VWF-inhibition

Description: Despite the high burden of disease, tissue plasminogen activator (tPA) formulations remain the only pharmacological agent to treat ischemic stroke. tPA has limited efficacy, constraints imposed by narrow therapeutic windows, and high risk of bleeding complications.  These limitations have propelled the search for more effective alternatives.  Recent studies emphasize the contribution of von Willebrand Factor (VWF) to these thrombi. This may explain the resistance of thrombi in the setting of acute ischemic stroke to fibrinolytic therapy. Furthermore, it has highlighted  VWF as a potential novel target for thrombolysis. BB-031, a short-acting, reversible RNA aptamer, inhibits VWF A1 and has displayed preclinical success and early clinical. However, the mechanism behind the thrombolytic activity of BB-031 remains unclear. We designed and employed an in vitro model capable of flow-dependent arterial occlusion and hemodynamically relevant thrombolysis to further investigate this, as well as to perform a preclinical comparison to tPA. This research seeks to shed light on the underlying mechanisms of high-shear thrombus resistance to fibrinolysis and explore VWF-inhibition as a more effective and safer alternative for the management of acute ischemic stroke. We aimed to evaluate the efficacy of BB-031 in comparison to tPA in the context of high-shear thrombolysis. Results from this study have unearthed additional insights into arterial occlusion and its underlying mechanisms.

Mentor: Dr. Susan Shea