The work presented in this thesis was performed at the Pediatric Endocrinology Unit, Department of Women’s and Children’s Health (KBH) and Department of Molecular Medicine and Surgery, Center for Molecular Medicine (CMM), Karolinska Institutet (KI), Stockholm, Sweden and at the Program on Developmental Endocrinology and Genetics (PDEGEN), National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, MD, USA.
This work was supported by grants from the Swedish Research Council, the Swedish Society of Medicine, HKH Kronprinsessan Lovisas Förening för Barnsjukvård, Wera Ekströms Stiftelse för Pediatrisk Forskning, Märta och Gunnar V Philipsons Stiftelse, Sällskapet Barnavård, Stiftelsen Frimurare Barnhuset i Stockholm, and Karolinska Institutet.
I wish to express my sincerest gratitude to all my mentors, colleagues, friends, and family who have contributed to the completion of this thesis. I especially want to thank the following people:
My main supervisor, Ola Nilsson, for steadfast support since 2005 when I first started medical research, inspirational role model as a physician-scientist, constant availability, invaluable discussions, picturesque and thought-provoking runs, humor, integrity, trust, and friendship.
My co-supervisor, Gunnar Norstedt, for creating an enriching research environment at CMM, facilitating educational and engaging group meetings, providing helpful feedback and suggestions, and making me feel welcome in a new group and foreign country.
My external mentor, Phillip Messersmith, for providing exceptional research training during my M.Sc. at Northwestern University, Evanston, IL, USA, inspiring me to use creativity and imagination in approaching scientific problems, and offering unconditional support and advice when needed.
My unofficial co-supervisor, Jeff Baron, for providing my first opportunity in medical research at NICHD, continuous guidance in the study of growth plate cartilage, inspirational role model as a teacher and mentor, and enlightening literature recommendations.
The Nilsson group to which it has been a privilege to be part of. Ane Andrade for guidance when I first started working at CMM, wonderful company while exploring Sweden as tourists, and friendship. You have taught me to value relationships even when academic responsibilities make it inconvenient. Stephan Späth for having high expectations for me as a Ph.D. student, enjoyable collaboration in the lab, introducing eclectic styles of music including the Bulgarian bagpipe and Mongolian throat singing, and friendship. I have learned that in science “no risk, no reward” and you know the rest. Ellie Landman for helpful discussions and collaboration in the lab,
refreshing coffee breaks, sharing big dreams for scientific discovery, and friendship.
Your meticulousness and organizational skills in the lab have hopefully rubbed off on me. My summer student, Amalina Che Bakri, for sharing a passion for medicine, having a curiosity and open mind to study the growth plate, and the privilege of teaching.
The Norstedt group for making me feel at home in a foreign country. Mattias Vesterlund for camaraderie, enjoyable conversations, and teaching me the difference between an ale and a lager. John Flanagan for good energy and leadership in the lab.
Fahad Al-Zadjali for amusing stories and good laughs. Diego Iglesias Gato for help in the lab and enjoyable conversations. Jin Hu for pleasant company and discussions.
Daohua Lou for nice conversations and providing me housing that one time. My sincerest appreciation also goes out to Petra Tollet-Egnell, Sandra Dunger, Torbjörn Persson, Anna Nilsson, Carolina Gustavsson, Amira Said Al-Kharusi, and Erik Wahlström.
The Baron group for making me feel like part of a family. Kevin Barnes for always being dependable and prompt in assisting in the lab, enjoyable conversations on diverse subjects, and demonstrating admirable dedication and consistency to your career. Youn Hee Jee for constant encouragement during difficult times, motivation to study and work hard, precious company in and out of the lab, memorable adventures, and friendship. You have taught me to aim high with my goals and pursue eudaimonic as opposed to hedonic happiness. Julian Lui for showing me the tricks of the trade in scientific research, collaboration in figuring out in situ hybridization, sharing the joys and frustrations of life in science, and friendship.
Katerina Nella for warmhearted company in the lab, wisdom and advice regarding medicine, amusing stories during medical training, and piquing my interest to visit Greece. Crystal Cheung for pleasant company in the lab, sharing the experience of being a doctoral student, and walking me through how to do a western blot. I also want to express my sincerest gratitude for your support and kindness: Angela Delaney, Fariha Kamran, Petricia Forcinito, Elizabeth Parker, Rachel Gafni, Rose Marino, Anita Hedge, and Iris Pelsma. My summer students, Abigail Paulson and Ashley Mathieu, for enthusiasm, diligence, open-mindedness to learn, and the privilege of teaching.
My friends and colleagues in the Pediatric Endocrinology Unit and KBH for a friendly environment and always welcoming me back with open arms. Susanne Hallberg for the indispensable help and sincere kindness you have given me. Olle Söder for an extraordinary job heading the unit. Lars Sävendahl for helpful questions and feedback. Andrei Chagin for helpful ideas and discussions. Eva Pontén for useful suggestions and talks. Cecilia Camacho-Hübner for enthusiasm and passion for science. Martin Ritzén for an inspiring example of dedication and contribution to the field. Astrid Häggblad for helping me navigate through the doctoral program. I also want to express my deepest gratitude for your support and kindness: Yvonne Löfgren Blomquist, Christine Carlsson-Skwirut, Mi Hou, Farasat Zaman, Emma Eriksson, Paola Fernández Vojvodich, Elham Karimian, Katja Sundström, Bettina Cederquist, Maryam Irvani, Therese Cedervall, Emelie Benyi, Thibault Bouderlique, Phillip Newton, and Karuna Vuppalapati.
My friends at the Karolinska Institutet for genuine support and kindness: Anna Maria Matino, Cornelia and Martin Gujer, Will Adams, Cecilia Lourdudoss, Salva Gomez Carretero, and Konstantinos Georgiou.
My friends at the National Institutes of Health for camaraderie and making life in the lab more enjoyable: Dez Taylor-Douglas, Sophie Liu, Lorna Smith, Jenna Shapiro, Christine Shieh, Jennifer Zhang, and Clara Cheng.
The collaborators of my papers, Andrea Vortkamp, John Bacher and Sohyun Ahn, for expertise and essential contributions to this thesis.
The owner of Histoserv Inc, Pratibha Vohra, for helpful suggestions regarding histology and essential contributions to this thesis.
The people who took care of the animals behind the scenes, Joanne Smith, Elias Gonzalez, Ndifor Prosper, and Dora Alenjandra and Craig Barr, for dependability and essential contributions to this thesis.
The people who provided me housing, Victoria Jonsson, Natalia Leliouk, and Barbara Disckind, for a safe environment and openheartedness.
My friends at Penn State College of Medicine for heartwarming support, encouragement, and blessings throughout my pursuit of this thesis: Andy Hoover, Ki Chang, Punit Singh, Paul Mathew, Jade Price, Angelica Mazzarini, Brittney Hacken, Lindsay Smith, Matt Wolfgang, Jared Nissley, and Chris Weber.
My beloved family and close friends for unfailing love, support, and encouragement:
my parents, Robert and Lun Chau, my grandmother, Sheut Chow ( ), my sister and brother-in-law, Lily Chau and Rodin Max Hai-Jew, Kiwi and Coco, the Yan family (Samantha, Iris, and Jimmy), the Leung family (Rachel, Teresa, and Samson), the Wong family (Joyce, Grace, Christina, and Godfrey), the Wong family (Andrew, Beverly, Calvin, Soon, and Eric), the Wong family (Anthony, Mitchell, Tai, and Rich), the Galbreath family (Jessica, Nic, Sarah, Nick, Lei, and Jeff), the Wilson family (Shelly and George), the Lam family (Seng, Maddy, and my grandmother, Kwan Kam Foon), my best buddy and his family, Johnny, David, Liza, and Gordon Chen, Richard and Janet Benney, and Justin and Christa Brask.
Finally, I wish to express my sincerest gratitude to the world-class medical university, Karolinska Institutet, for providing me this opportunity.
THANK YOU!