Citrullination and Thrombosis | Ronak Tilvawala |

Summary :
⁣Increased protein citrullination is linked to various diseases including rheumatoid arthritis (RA), Lupus, and cancer. To understand the role of citrullination in pathophysiology, one needs to comprehensively identify the citrullinated proteins associated with these diseases and link them together. Towards this end, we used a chemoproteomic approach to define the RA-associated citrullinome. The identified proteins include numerous serine protease inhibitors (SERPINs) and serine proteases. Many of these serine proteases and SERPINs are involved in regulating hemostasis and fibrinolysis – the biological processes that maintain proper blood flow. The delicate balance between proteolytic and inhibitory reactions in hemostasis and fibrinolysis, can be disrupted, resulting in pathological conditions such as thrombosis and abnormal bleeding. Herein, we demonstrate that citrullination of P1-Arg containing SERPINs alters their activity under physiological conditions, thereby altering normal homeostasis. Overall, these data advance our understanding of the roles of citrullination in thrombosis and suggest that extracellular protein arginine deiminase (PAD) activity can modulate protease activity with consequent effects on SERPIN-regulated pathways.


About Author :
⁣Ronak Tilvawala received her bachelor’s degree in pharmaceutical sciences in 2007 from India. She received her PhD degree in chemistry in 2014 from Wesleyan University, USA. From 2014 to 2016, she worked as a postdoctoral fellow at Texas A & M medical school where she developed novel biosensors for the detection of early-stage tuberculosis. In 2016, she moved to UMass medical school, where she developed a novel chemoproteomic approach to detect citrullinated proteins from biological samples. In 2020, she joined the department of Molecular Biosciences at the University of Kansas as an Assistant Professor. The current projects are focused on mainly two areas: 1) understanding how protein citrullination disrupts the regulation of key protease cascades leading to thrombosis and inflammation in multiple pathologies; and 2) understanding how viral proteases interfere with host protease cascades to invade into the host system. She has co-authored more than 18 publications.