Immunoengineering Trainee Seminar

Featured Speakers: 
 

“What Stops Menstrual Bleeding? From Spiral Arteriole Hemodynamics to Heavy Menstrual Bleeding” - Raphaelle Dodart, Ph.D. Student, David Ku, Advisor

Abstract

Heavy menstrual bleeding (HMB) is common, but the mechanisms that control blood loss during menstruation remain poorly understood. Computational analysis of menstrual blood loss and uterine vascular anatomy suggests that spiral arterioles are a plausible major source of menstrual bleeding. The high shear rates generated within these small vessels may also favor shear-induced platelet aggregation (SIPA), providing a potential mechanism for rapid hemostasis following endometrial shedding. An ongoing clinical study at Georgia Tech examines whether dysfunction in SIPA and primary hemostasis is present in a subset of women with HMB. This work connects spiral arteriole hemodynamics with clinical measurements of hemostatic function to better understand why menstrual bleeding becomes excessive in some women.

“Synthetic Notch Circuits Enable In Vivo Measurement of Endogenous Forces on Immune Cell Receptors” - Menglan Li, Research Scientist, Georgia Tech 

Abstract

Understanding how mechanical forces influence the signaling pathways of immunoreceptors is essential for advancing research in immunology and immunotherapy. Despite in vitro evidence of endogenous forces exerted by immune cells on immunoreceptors, in vivo measurement has been challenging due to technological limitations. Here, we present a novel technology platform based on synthetic Notch (SynNotch) circuits, enabling in vivo reporting of cell-generated forces on specific receptors. Our platform utilizes the mechano-sensitive properties of the Notch receptor, re-engineering it by replacing its ligand-binding domain with a single-chain variable fragment (scFv) of an antibody targeting the receptor of interest. The SynNotch receptor's activation induces the expression of a reporter gene. By adoptively transferring receiver cells expressing SynNotch into animals, we can measure the forces exerted by sender cells on the target receptor in vivo. We validated this platform using T cells as receiver cells and B cells as sender cells, with CD40 as the target receptor. Our results showed that B cells exert forces on CD40-SynNotch bonds, leading to the activation of SynNotch at forces around 2.4 pN per bond, increasing to a plateau at approximately 6.4 pN per bond. This mechanotransduction significantly influenced B cell signaling. This technology provides a powerful tool for investigating receptor-mediated mechanosensing and mechanotransduction in various biological contexts.

The Immunoengineering Training Seminar Series is supported by the NIH T32 Research Training Program in Immunoengineering and housed within the Center for Immunoengineering at Georgia Tech.