Wayne State University Wayne State University Dissertations January 2019 Utilizing Immunopet To Measure Tumor Response To Treatment In Breast Cancer Brooke Mcknight Wayne State University, [email protected] Follow this and additional works at: https://digitalcommons.wayne.edu/oa_dissertations Part of the Bioimaging and Biomedical Optics Commons, and the Biology Commons Recommended Citation Mcknight, Brooke, "Utilizing Immunopet To Measure Tumor Response To Treatment In Breast Cancer" (2019). Wayne State University Dissertations. 2176. https://digitalcommons.wayne.edu/oa_dissertations/2176 This Open Access Dissertation is brought to you for free and open access by DigitalCommons@WayneState. It has been accepted for inclusion in Wayne State University Dissertations by an authorized administrator of DigitalCommons@WayneState. UTILIZING IMMUNOPET TO MEASURE TUMOR RESPONSE TO TREATMENT IN BREAST CANCER by BROOKE N. MCKNIGHT DISSERTATION Submitted to the Graduate School of Wayne State University, Detroit, Michigan in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY 2018 MAJOR: CANCER BIOLOGY Approved By: Advisor Date DEDICATION I dedicate this to all of the little girls who dream of seeing, learning, and becoming “more”, and to the people who support them every step of the way. To those of you who did that for me - thank you for giving me “more”. i ACKNOWLEDGEMENTS Throughout my graduate career, I have received the support and guidance from many people who deserve my appreciation. This work would not have been possible without the support of my advisor, committee, colleagues, family, and friends. Advisor I would like to express my sincere gratitude to Dr. Nerissa Viola, who has been my advisor throughout my dissertation work. Thank you for providing me with an environment to learn, design projects, and cultivate the skills necessary to have a successful career. Without Dr. Viola, this project would not have been possible, and I am grateful for her wealth of knowledge and generosity that made it happen. Committee Throughout my dissertation research, I have received advice and encouragement from each of the members on my committee. Each mentor has provided me with valuable insight and expertise that has taken my project to another level. Dr. Anthony Shields has provided a clinical perspective to my project and has been an invaluable source of knowledge regarding imaging aspects of the experiments. Dr. Wei-Zen Wei has provided immunology expertise, without which the fourth chapter of this dissertation would cease to exist. She has also served as a co-mentor during my F-31 grant submission. Dr. Julie Boerner has been an advocate of mine since I was recruited into the program under her direction and has since provided vital insight into the biology of Src and the HER family signaling pathway. Dr. Matt Allen has challenged me with thoughtful questions regarding the chemistry of my projects, which has allowed me to gain this experience*. Each of my ii committee members has provided me with mentorship for which I am especially grateful. Viola Lab Each member of the Viola lab has been a great source of support and friendship during my entire time in the lab. Jordan White has been a wonderful friend and peer. I am thankful for his help in keeping the lab organized and performing/troubleshooting experiments side-by-side on the days when I needed a little extra push to get going. I also am grateful for our similar taste in music, and the ability to rock out to 90s pop hits, 2000s hip hop, and Christmas music year-round. Dr. Akhila Kuda-Wedagedara has been a surrogate “big brother” in the lab, sharing with me his insights into the PhD process, helping me with the chemistry of my experiments, and acting as a sounding board when designing experiments. Colleagues I would also like to thank Dr. Heather Gibson, Claire McCarthy, and Joyce Reyes for their hands-on involvement in the project described in chapter 4. Agnes Malaysa, Dr. Lisa Polin, Kirk Douglas, Dr. Jessica Back, Xin Liu, Dr. Tom Mangner, Karri Stark, and the DLAR staff have all provided me with the support, knowledge, and hands-on assistance with various parts of my experiments, and I would have been much less organized without your attention to detail and expertise. Thank you all. Cancer Biology Graduate Program Of course, I must also thank the Cancer Biology Graduate Program for their continued support and guidance through this entire process. I would like to thank Dr. Larry Matherly for his management of the CB program and his interest in the success of the students. To Dr. George Brush, thank you for all of your input and advice over the years, iii and for always making sure I have submitted my IDP correctly and on time. And to Nadia Daniel, thank you for always making sure the “trains run on time” – without your continued enthusiasm and dedication for the program and my personal success I would not be where I am today. Additionally, I would like to extend my sincere gratitude to the steering committee members from 2014-2018 for fostering a research-focused environment for the students to flourish. Additional Significant Support I must now thank the students, whom without there would be no program. I would like to specifically thank a few of the graduates who have provided me with invaluable insight, support, encouragement, and stories – Drs. Stephanie Blocker, Tom McFall, Rayna Rosatti, Chris McHugh, and Dan Feldmann. And to a few of the current students who are my confidants, friends, and consultants – Josh Heyza, Anthony Guastella, Laura Hurley, Nico Moses, Ethan Brock, Allison Mitchell, Kayla Connor, Adrianne Wallace- Povirk, and Josh Mandella – thank you for always being a text message, lab-themed snapchat, or Starbucks break away. I would additionally like to thank Dr. David Ginsburg, Dr. Rami Khoriaty, Dr. Leslie Everett, and Suzann Labun for taking a chance on me back in 2013 when I was a junior at the University of Michigan. Without your support and training, countless letters of recommendation, abstract and CV editing, and continued advice, I would not be where I am today. Family I would like to acknowledge the people whose battles inspired me to apply for this PhD in particular. First, to my grandma-angel, Marilyn Gravila, who lost her 30-year battle iv in 2000. Next, to my dad, and my cousins Brad Foster and Derek Adams, who have won or are still fighting their battles. Finally, to the countless family-friends who have allowed me to probe into their experiences for the purpose of expanding my cancer knowledge – your kindness in sharing your stories has made me a better scientist. I would like to extend the largest thank you to my immediate family. None of my accomplishments would have been possible if not for your constant support, encouragement, and love. I want to give the most heartfelt thanks to everything they have done to keep me motivated throughout this process. To my dad, Mark McKnight, thank you for always being my confidence – even when I am not sure of myself. You have always pushed me to be better and do more, and I am forever grateful. I would like to thank my mom, Michelle McKnight, who has taught me everything I know about being a strong and intelligent woman. You have always been my rock and sounding board, and I thank you for your constant support. Together, you have provided me with a solid foundation to build a life upon, and I couldn’t have done any of this without your financial support. Thank you from the bottom of my heart for the sacrifices you both made to provide me with a wonderful life. I would like to thank my “bonus family” – John, Cheryl, Jared, and Jordan Dickow. You have all been here with me since sophomore year in college, so I feel as if you’ve been a part of this process every step of the way. Thank you for all of the phone calls, advice, and your constant curiosity in what I am doing, even if after a few minutes of explanation you wish you hadn’t asked after all. I will forever cherish the holidays, weekends, and game nights spent together, that provided me with a little “escape” from v my constant studying. Last but not least, I thank my husband, Justin Dickow. Who would’ve thought that back in 2011 when we met and began our relationship by spending countless hours studying at the BBB building and the Dude at the University of Michigan that we were setting up our lives for the next decade. Without your continued support, coaching, and “tough love” (when it comes to academics and my study habits), I would have never learned how to push myself academically or been able to complete a PhD. I owe this all to you and am so glad we can share in the fun times now that school is over! (for now…) vi TABLE OF CONTENTS DEDICATION ................................................................................................................... i ACKNOWLEDGEMENTS ................................................................................................ii TABLE OF CONTENTS ................................................................................................. vii LIST OF TABLES ........................................................................................................... xii LIST OF FIGURES ........................................................................................................ xiv LIST OF ABBREVIATIONS .......................................................................................... xvii CHAPTER 1: INTRODUCTION ......................................................................................