Notice and Invitation Oral Defense of Doctoral Dissertation The Volgenau School of Engineering, George Mason University Md Daud H. Khan Bachelor of Science, George Mason University, 2008 Master of Science, University of Bridgeport, 2015 Evaluating the Role of ER Stress and Nicotine in Cancer Metabolic Pathways Wednesday, July 24, 2019, 11:00am - 1:00pm Krasnow, Room 229 All are invited to attend. Committee Dr. Remi Veneziano, Chair Dr. Juan Cebral Dr. John R. Cressman Dr. Carolina S. Morales Abstract Despite advancements in technology and discovery of several signaling pathways involved in metastasis of breast cancer, interlinking these processes has been a major challenge along with establishing hierarchical importance of each. The involvement of nicotine, though a known carcinogen, in breast cancer metastasis is still unclear due to the non-clinically relevant concentrations being used in most investigations. The exact type of nicotinic acetylcholine receptor (nAChRs) mediating the cellular actions is yet to be determined as various reports yield contradictory claims. Several investigations have reported the ability of nicotine to directly or indirectly induce epithelial-to-mesenchymal transition (EMT), an important process in the metastatic cascade, in certain cancer types. However, its potential role in eliminating endoplasmic reticulum (ER) stress has not been explored. In this investigation, we aim to interlink and establish the hierarchical framework of 2 critical oncogenic pathways, ER stress and EMT, and investigate the potential role of nicotine in facilitating ER stress elimination during chemically induced EMT in breast cancer via á9 nAChRs.