New methods and tools for optimizing translational precision photomedicine

Abstract

First and foremost, I must acknowledge my advisor, Bryan Spring, whose steadfast support and encouragement was fundamental to the success of this dissertation. Bryan's mentorship has been invaluable in directing my development as a scientist, and his kind and generous friendship has made me a better person. To the rest of the Spring Lab members, especially Ryan and Kai, I give my thanks for all of their hard work and thoughtful discussions. Also, my sincerest thanks to our coop students, Gabby, Julia, and Alejandro, for being such excellent students and colleagues. It was truly a pleasure working with and learning from them. Much of this work would not have been possible with out help from Dr. Tayyaba Hasan and her team at the Wellman Center for Photomedicine at Massachusetts General Hospital. I am grateful for the opportunity to work and learn in their lab. My thanks go to Drs. Aki Palanisami, Girgis Obaid, Shubhankar Nath, and Saad Mohammad for their patient instruction and thoughtful discussions, as well as Mike Pigula and Joseph Swain for their time and help with experimentation. I was also quite fortunate to collaborate with Professor Sunny Zhou and Amissi Sadiki in the Northeastern Chemistry Department, two brilliant chemists and generous colleagues who supported this work and whose enthusiasm for antibody conjugate synthesis is unrivaled. Finally, I would like to thank my thesis committee members, Professors Mark Williams, Meni Wanunu, and Anne van de Ven, for their support of this dissertation. There are quite a few more who deserve acknowledgment for providing me with indirect, but no less valuable, support. My gratitude goes to, in chronological order: my high school physics and math teachers, Brock and Amy Hammill, for instilling in me a worldly curiosity that sparked my career in STEM; my undergraduate physics professors, particularly Drs. Richard Ditteon, Sudipa Mirta-Kirtley, Renat Letfullin, and Paul Leisher, for their deft instruction and for enabling exploratory extracurricular research projects; and to Drs. Suzanne Gronemeyer and Claudia Hillenbrand for facilitating an eye-opening summer internship at St. Jude Children's Research Hospital. Finally, my fellow graduate students at Northeastern, especially Andrew, Chad, James, Amin, Gustavo, and Tanvi, have my utmost respect and gratitude for providing a wonderful community and culture throughout our graduate studies. Most of all, I must thank my family for their unwavering love and support. List of Tables Chapter 1: Introduction Chapter 2: A custom LED light source for benchtop photomedicine Chapter 3: Site-specific synthesis of photoimmunoconjugates for taPIT Chapter 4: Photoimmunotherapy in a 3D cancer-immune cell co-culture Chapter 5: Applying taPIT to treat disseminated cancer metastases in vivo 57 Chapter 6: Video-rate unmixing of multiplexed hyperspectral images References 95 Appendicies