IBSC-BME PhD Defense Announcement for Brenna Vaughn (L. Solorio, advisor) Everyone is invited to attend the public presentation beginning at 10:00am. Title: Transglutaminase-2 Enables Actin-Microtubule Driven Resistance to T-DM1 in HER2-Overexpressing Breast Cancer Cells Date: Friday, June 6th Time: 10:00am Location: MJIS 2001 and Zoom - https://purdue-edu.zoom.us/j/99831119513<https://nam04.safelinks.protection.outlook.com/?url=https%3A%2F%2Fpurdue-edu.zoom.us%2Fj%2F99831119513&data=05%7C02%7Cbmeroundtable-list%40ecn.purdue.edu%7Cdba1982a1b474473f6df08dd9d1f7bff%7C4130bd397c53419cb1e58758d6d63f21%7C0%7C0%7C638839480728633760%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=zU9Hh6KdcCNtBpvup15bRLAN3qr%2FtY7ZoK6qpG5hTqU%3D&reserved=0> Committee: Dr. Luis Solorio (Advisor), Dr. Michael Wendt, Dr. Leopold Green, Dr. Hector Gomez Abstract: Recurrence and progression are important measures of efficacy in evaluating cancer drugs. When cancer cells develop resistance to a therapy, cancer can progress or recur at sites local or distant to the treated disease. In recent decades, antibody-drug conjugates have improved the ability to target cancer cells and deliver chemotherapeutic agents with higher specificity. However, recurrence and progression remain common with these drugs. In the present study, we describe a novel mechanism of resistance to the antibody-drug conjugate T-DM1 in HER2 overexpressing breast cancer cells. Although there are several known mechanisms of resistance to T-DM1, it is not fully clear why T-DM1 preforms much worse than the newer drug T-DXd, the same targeting antibody with different cytotoxic payload. Addressing this knowledge gap is vitally important to inform further research and development. Cells become resistant when exposed exclusively to the cytotoxic payload of T-DM1 in the absence of the associated antibody, confirming resistance arising from the microtubule inhibitor. Increasing density of cells and subsequently higher β1 integrin expression correlated with increasing survivability of escalating T-DM1 dose. Further, overexpression of the matrix stabilizing enzyme transglutaminase 2 (TG2) confers a survival advantage in chronic T-DM1 exposure. Inhibition of focal adhesion kinase and myosin II reverses this survival advantage. These facts indicate an a-actinin as a key mediator of resistance. We thus demonstrate the role of TG2 and β1 integrin in HER2 overexpressing breast cancer cells in gaining resistance to T-DM1 via an actin cytoskeletal adaptive mechanism. Zoom link: Topic: Brenna Vaughn's PhD Defense Time: Jun 6, 2025 10:00 AM Eastern Time (US and Canada) Join Zoom Meeting https://purdue-edu.zoom.us/j/99831119513<https://nam04.safelinks.protection.outlook.com/?url=https%3A%2F%2Fpurdue-edu.zoom.us%2Fj%2F99831119513&data=05%7C02%7Cbmeroundtable-list%40ecn.purdue.edu%7Cdba1982a1b474473f6df08dd9d1f7bff%7C4130bd397c53419cb1e58758d6d63f21%7C0%7C0%7C638839480728655506%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=tQHERbd1rpNJ8Wv%2FW8dSWDUYYs615uEhbahTBM6cJrY%3D&reserved=0> Meeting ID: 998 3111 9513 --- Join by SIP * 99831119513@zoomcrc.com<mailto:99831119513@zoomcrc.com> -- Join by H.323 * 144.195.19.161 (US West) * 206.247.11.121 (US East) Meeting ID: 998 3111 9513 -- Bmeroundtable-list mailing list Bmeroundtable-list@ecn.purdue.edu https://engineering.purdue.edu/ECN/mailman/listinfo/bmeroundtable-list