Cover Page
The following handle holds various files of this Leiden University dissertation:
http://hdl.handle.net/1887/62204
Author: Chen, X.
Title: Determinants of genome editing outcomes: the impact of target and donor DNA structures
Issue Date: 2018-05-16
List of publications
1. Chen X, Liu J, Janssen JM, Gonçalves MA. The chromatin structure differentially impacts high-specificity CRISPR-Cas9 nuclease strategies. Molecular Therapy-Nu- cleic Acids 8:558–563 (2017).
2. Chen X, Janssen JM, Liu J, Maggio I, ‘t Jong A, Mikkers H & Gonçalves MA. In trans paired nicking triggers seamless genome editing without double-stranded DNA cutting. Nature Communications 8:657 (2017).
3. Chen X, Rinsma M, Janssen JM, Liu J, Maggio I, Gonçalves MA. Probing the im- pact of chromatin conformation on genome editing tools. Nucleic Acids Research 44:6482-6492 (2016).
4. Chen X, Gonçalves MA. Engineered viruses as genome editing devices. Molecular Therapy 24:447-457 (2016).
5. Maggio I*, Chen X*, Gonçalves MA. The emerging role of viral vectors as vehicles for DMD gene editing. Genome Medicine 8:59 (2016). (*co-first author)
6. Maggio I, Stefanucci L, Janssen JM, Liu J, Chen X, Mouly V, Gonçalves MA. Se- lection-free gene repair after adenoviral vector transduction of designer nucleases:
rescue of dystrophin synthesis in DMD muscle cell populations. Nucleic Acids Re- search 44:1449-1470 (2016).
7. Maggio I, Holkers M, Liu J, Janssen JM, Chen X, Gonçalves MA. Adenoviral vec- tor delivery of RNA-guided CRISPR/Cas9 nuclease complexes induces targeted mu- tagenesis in a diverse array of human cells. Scientific Reports 4:5105 (2014)
Addendum / 173
Curriculum Vitae
Xiaoyu Chen was born on September 6th, 1990 in the city of Xingtai, Hebei Province, China. During 2006-2013 she was enrolled in a 7-year bachelor-master combined program of clinical medicine in Hebei Medical University, Shijiazhuang, China.
From 2006 to 2008, she studied general college courses in Nankai University, Tianjin, China. She received her BSc degree in medicine in 2011 and MSc degree in neurolo- gy in 2013. From 2011 to 2013, she worked in the laboratory of Professor Chunyan Li to study the neurodegenerative disease ALS using the SOD1G93A mouse model. Dur- ing her studies in Hebei Medical University, she received a national undergraduate scholarship in 2008 and a national graduate scholarship in 2011 from the Ministry of Education of China.
In the last year of her master study, she developed a great interest in gene therapy, whose goal is to target the root cause of diseases. Instead of becoming a medical doctor, after her graduation, she applied for a Ph.D. scholarship from the China Scholarship Council to pursue a research career in the Netherlands. In 2013, Xiaoyu started her Ph.D. studies in the group of Prof. Dr. Rob C. Hoeben under the supervi- sion of Dr. Manuel A.F.V. Gonçalves in the Department of Cell and Chemical Biolo- gy at the Leiden University Medical Center (LUMC).
Throughout her Ph.D. studies, she focused on investigating high-fidelity genome engineering strategies, especially those based on Cas9 “nickases” and target site-containing donor DNA molecules. Next to this research, she has also probed the impact of higher-order chromatin on the performance of gene editing tools, and on the balance of different DNA repair pathways. These studies were presented in this thesis. Currently, Xiaoyu Chen is looking forward to translate genome engineering technology from the bench to bed side.
Acknowledgments
This is it, an exciting adventure of Ph.D. I thought it might be about survival, but turns out to be epic. Surrounded by so many amazing people, glancing back, I know that, the fortune always smiles upon me.
I would like to express my heartfelt gratitude to my promotor Prof. Dr. Rob C. Hoe- ben who showed me the essence of leadership: open-mind, generosity, and ration- ality. I want to express my deepest gratitude to my supervisor Dr. Manuel A.F.V.
Gonçalves for unveiling me the beauty of science, including its sweets and bitter- ness. He guided me with patience and earnest instruction, and taught me how to make sense out of mess and how to make a win out of loss.
Special tribute go to my paranymphs Igno and Jin, who always encourage me when- ever I am drained out of energy and cheer me up on every single milestone I made. I thank Kim for her tremendous help in assisting my projects and organizing the lab. I also thank the people that I have worked with for their team spirits and camaraderie:
Francesca, Hidde, Ivan, Luca, Marcela, Marrit, Marteen, Qian and Sara. My thanks also go to the colleagues in LUMC–Amiet, Anke, Anna, Arnaud, Diana, Erik, Gelilla, Harald, Henrique, Iris, Jan, Jiang, Lussi, Maaike, Marjolein, Martijn, Peter, Ron Wol- terbeek, Sijia, Steve, Thilo, Timo, Tobias, Vera, Willem, Yongsheng, Yvonne–with whom I shared meetings, paper celebrations and birthday cakes. My sincere thanks also go to Prof. Peter ten Dijke, who once told me “Just be yourself” and relieved me from self-doubt.
I also thank my Chinese friends in Leiden–He Nan, Jiali, Yifei, Jianhui, Xinpei, Yan- ming, Jinxian, Jian Yang, Guangchao, Kaifeng, Channa, Wenbo, Xiaoke, Zhiwei, Pu- ning, Yingguang, Zhang Rui, Zhenyu, Fuyu, Qiuyin. The sharing trips and food have been great solace since we are thousands of miles away from home.
I would also like to express my special thanks to professor Chunyan Li, who plant- ed the seed of scientific research in my mind and whose support stand by me since 2011.
Last, I would like to dedicate this thesis to my parents and brother Yanpei, who are always supportive for my dream, though, equally concerned on my safety.
The journey ends; the quest still goes on.
Now, peace and serenity.
Addendum / 175
