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The versatile nature of MIF (macrophage migration inhibitory factor) in chronic lung diseases

Florez Sampedro, Laura

DOI:

10.33612/diss.135375699

IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite from it. Please check the document version below.

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Publication date: 2020

Link to publication in University of Groningen/UMCG research database

Citation for published version (APA):

Florez Sampedro, L. (2020). The versatile nature of MIF (macrophage migration inhibitory factor) in chronic lung diseases. University of Groningen. https://doi.org/10.33612/diss.135375699

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Acknowledgements

A little more than four years have gone by since I started my PhD journey and I can’t believe I’m finally writing these words. I feel immensely grateful for getting the chance to go through this personal and scientific journey. And while the PhD experience on its own teaches you to be professional and persistent, it’s the people around you that fill you with inspiration, admiration and gratitude.

First of all I would like to thank my supervisors Barbro Melgert and Gerrit

Poelarends, for choosing me for this position and giving me the opportunity to

develop this project. I always thought that the two of you were a yin and yang-kind of supervisor team: Barbro (female side), drinks tea and dislikes coffee, loves sweets and is usually calm and more introverted; Gerrit (male side), drinks coffee, prefers savory over sweet things, and is very energetic. These differences actually contributed to a more balanced work environment during this journey.

Barbro, we have always shared a love for biology and immunology, but thanks to

you I discovered my love for macrophages and my appreciation of good statistics. You helped me become more independent as a researcher and you pushed me to just jump in the water when I was afraid of starting a challenging experiment. You used to say something like “You have to start somewhere”, which I now use as a sort of mantra even in my life outside the lab. I always valued your humane approach in science, not wanting to make people look or feel bad for what they were missing in their research and remembering to “be kind with your comments because you don’t know how much people struggled to get these results”. You might look quiet and calm but you are also a very passionate person when it comes to health policies and healthy habits. I admire your strong interest and critical views on these topics and I believe that those and your research can really help make this a better world. I wish you lots of luck (we sure know firsthand how important luck is in science!) inside and outside the lab and great health to keep on enjoying the beauty of biology.

Gerrit, you were always there to make sure things were going well with the project

and with me. You always offered advice, pro-active strategies and prompt answers to all my questions. I always appreciated how much interest you showed in our meetings by asking good questions, taking notes and your permanent willingness to learn with us. Having you in our meetings provided a different perspective and gave the project a strong input from the molecular side. In the last year of my PhD I realized that we had more in common than I thought and I learned a lot from our talks about personal and professional life. Thanks to you I know a couple of tricks that work

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for organized people like us and I will always remember your advice: “don’t stress so much, it will eventually affect your health and it’s not worth it”. I guess is more about being proactive than pro-worrying, right? I admire your passion, efficiency and dedication for research and I hope you get many healthy years to continue doing what you love and keep on building your lab.

I thank the MPDI master, the GRIP, and Prof. Dr. Erik Frijlink for their financial support throughout my PhD project. Thanks to you I was able to do what I love for four whole years. To Prof. Frank Dekker, Prof. Gerard Koppelman, and Prof.

Martine Smit, thank you for accepting to be part of the reading committee of this

thesis and providing feedback for its improvement.

To all members of Melgert’s group, a.k.a. the macrophage squad, I want to thank you for your company, constant help and collaboration during these past years. I’ll always remember you guys: Habibie, for how hard you work and for your great sense of collaboration and selflessness; Gwenda Vasse, for your dedication and discipline in science, music and sports; Sara Russo, for your friendly and kind personality;

Fransien van Dijk, for your calm and kind voice and for your sense of humor about

life; Anienke van der Veen, for your constant support and encouragement and for sharing 4 years of personal development and a full US conference/adventure with me. Thanks for being there! Shanshan Song, for your hard work and for sharing with me samples, protocols, publications, discussions, and worries about the PhD and the crazy world of MIF-DDT. Marina de Jager, for your great kindness, your constant offer to help, and for being a lovely officemate (and Dutch trainer hehe) in the last months of my PhD. To Carian Boorsma, Christina Draijer and Adhyatmika, thanks for your guidance and company during the first years of my PhD. I wish you all the best in your personal and professional lives!

I want to thank all the members of the department of Chemical and Pharmaceutical Biology for their help, collaboration, and support during all these past years. In particular I want to thank Lieuwe Biewenga for his essential guidance and help with cloning and protein purification; Tjie Kok for helping me and providing all the materials to study CD74-MIF interaction; Robert Cool, Ronald van Merkerk, Rita

Setroikromo, Pieter Tepper, Yvonne Mettes, and Janita Zwinderman for their

help in matters of science, techniques, and paperwork. Lastly, I want to thank Abel

Soto, for deciding to work with me in the complex world of MIF and senescence. I’m

extremely grateful that I could have you as my lab partner for this part of the project. You truly supported me going through extensive experiments and complicated literature, you taught me a lot about cellular senescence and cancer biology, and

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you always lifted my spirit with your company, laugh and enthusiastic way of doing research. I admire your vast knowledge and your tenacity and I have no doubt that you’ll have a bright professional future. It’s been great sharing so many scientific and non-scientific moments with you and I hope we get to have many more in the coming years. I also extend my gratitude to Dr. Marco Demaria, for supporting this collaboration and for the critical insights on cellular senescence. To Wim Quax,

Hidde Haisma, and Frank Dekker, and all members of the department, thank you

for the interesting discussions during the Thursday seminars.

In the last year of my PhD Melgert’s group became part of a new department,

Molecular Pharmacology. While I was part of this group for only a few months I

really felt welcomed by Martina Schmidt, Reinoud Gosens, Amalia Dolga, and all other members of this great department. I was particularly grateful for being part of this group during the COVID19 pandemic, as even being a new member at the end of the PhD I felt included and felt their immense support and warmth during these hard times.

For the most time in my PhD I was part of the department of Pharmacokinetics,

Toxicology and Targeting. While I’m officially part of other divisions, a big part

of my heart belongs to the people in this department because they accompanied me and supported me during the worst and best times of my PhD journey. First, to

Gillian Nieuwenhuis-Dempsey, for being the supporting, helpful, funny and friendly

person you are. With your playful personality you always managed to brighten our days, even in hard times, in and outside the lab. Thanks for being truly present! To

Eduard Post, for using your vast knowledge and infinite energy to help us solve

every single issue we could encounter, even when it was not your duty. That and your great sense of humor made you a great colleague and a wonderful member of our GoT club. To Catharina Reker-Smit, for your constant help around the lab because many of us would not have made it through the PhD without you! Your knowledge, experience, accuracy and organization made it possible for us to do things well in the lab. I also want to thank the current and previous members of the group that accompanied me during this period, Geny Groothuis, Klaas Poelstra, Anna Salvati,

Leonie Beljaars, Inge de Graaf, for the friendly and supportive environment in the

department and your interest during my presentations; to Viktoriia Starokozhko and Natalia Estrada, additional thanks for your guidance in the academic life and your friendship outside the lab.

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Additionally, to the PhD students, Keni Yang, Hector Garcia, Harita Yedavally, and Aldy Aliyandi, and the many others that already left, for contributing to a great atmosphere in and outside the lab. I wish you guys the best with the rest of your PhDs and research careers!

I also want to thank all the members of the GRIAC team, for the high-quality research, the friendly environment, and for all the helpful suggestions for improving my research and PhD journey. I’ve learned a lot from all the meetings and I feel proud for having been a part of such a great team. I would like to thank some members in particular for directly contributing to my research journey.

In the first place I would like to thank Irene Heijink and Corry-Anke Brandsma for introducing me into the Lung -and GRIAC- world and for always helping me and encouraging me even after my master’s internship had ended. I admire your critical ways of thinking and I appreciate how friendly and helpful you both have always been with me. Choosing your project for my first master’s internship was one of the best decisions I’ve made and it opened a new world for me. Corry, additional thanks to you for your help with all patient-related data included in my PhD projects and with the challenging eQTL paper, because you always replied patiently and soon to my almost infinite list of questions.

To Machteld Hylkema and Janette Burgess, for their helpful and kind relation with us, the students, and for making the pathology meeting a space to train hard in presentation and discussion skills. There were difficult presentations at times, of course, but at the end of all meetings you were always offering solutions, ideas and help to make our projects as much picky-reviewer-proof as possible. Machteld, I met you already during my master’s internship and since then I’ve enjoyed your company and your way of seeing (and saying) things. I will always keep happy memories of the talks with you in hallways or during dinners, and all the advice you shared with us on how to be a tough female researcher in a male-dominated world. Janette, I will always remember and be grateful to you for offering your help to me during that difficult period when Barbro was recovering and none of my experiments seemed to work. I have learned a lot from you scientifically and I will no longer see the ECM as “just a scaffold”. I will always try to think of your “what is your research question?” when I’m trying to design an experiment, as it’s a simple but crucial question. To Alen Faiz and Maaike de Vries, for guiding me, helping me and teaching me about eQTLs and other complex genetic analyses. Alen, even since my master internship you were always available to help, look into data with me, and explain

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patiently the basis of molecular genetics. Throughout my PhD and still when you were back in Australia you were always willing to meet, call or skype to guide me through the complexity of these analyses. Also, despite your busy agenda you always took the time to ask how everything was going in my other projects and in my life and even offered to help and gave advice in many occasions. Maaike, I always enjoyed your company and the talks with you and I’m very happy that you were also part of the eQTL project, because you were always there to help me untangle our results and offered kind words of support and encouragement. Those are often forgotten among researchers and can actually make the difference between staying motivated and quitting.

Wim Timens, I met you during my master’s internship and I think I didn’t realize back

then how lucky I was to have you as part of our project. In our research circle, you’re the person everyone trusts and relies on for clinical and pathological assessments of lung samples. Most of the theses within the GRIAC depend on your knowledge of lung pathology, and for sure mine did! Despite your notoriety and immense knowledge, you were always willing to help and make appointments just to take a look with me at some lung sections and explain for the millionth time what was what. Thank you for your patience and for all you taught me!

To Hataitip Tasena, Roy Woldhuis, Kaj Blokland, Khosbayar Lkhagvadorj,

Corneel Vermeulen, Daan Pouwels, Marnix Jonker, Jacobien Noordhoek, Marjan Reinders-Luing, and Weird Kooistra, thank you for all your support with

samples, analyses, protocols, discussions and friendly conversations in and outside the lab. I wish you and all members of the GRIAC the best in your lives and research careers.

I also feel very fortunate to have wonderful friends (and great scientists) accompanying me for this moment: Berit Troost and Roberta Bartucci as my paranymphs, and Daphne Montizaan, and Olivia Díaz, as my ´honorary paranymphs´. These colleagues and officemates quickly became some of my closest friends in Groningen and since then we’ve shared our joy, pain, frustrations, worries, funny anecdotes, and great moments. B, It’s been 6 years since we met at our master internship at the UMCG. We’ve shared a lot together! (even the desk during our internship). I’m always extremely grateful to have you as my friend, for kindly understanding me as sensitive as I am, teaching me to manage that side of me, and for always being honest with me even when it’s a hard truth that I need to hear. You have taught me a lot over these years through your wise advice and supporting friendship. Roby, your big smile and strong hugs are the perfect reflection of your warm heart. Our

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overactive brains and common “Latin” culture united us and allowed us to share from the silliest thoughts to some deep fears. We have come a long way since sharing an office for the first time in 2015, although even back then we already knew we had a good connection. Daph, I admire how dedicated and compassionate you are. You’re a box full of surprises, because behind your strong dedication for science there’s a big fun world with motorcycles, trampoline jumps, guinea pigs, singing and painting. I feel very happy that I could share many of those other sides with you plus the many deep conversations about human interaction, professional careers and the future of human kind. Oly, it amazes me how kind, selfless and big your heart is! You’re always offering your help and comfort and you’re willing to go a long way for just a small gesture to lift our spirits. Your kindness and our endless conversations in Spanish always made me feel warmer, safer and closer to home (even if our homes are actually different countries hehe). Girls, the four of you have been an important support system during this challenging adventure and I feel extremely lucky and happy to have you in my life. I hope we continue to share many more great moments together in the future!

I also want to thank my friends outside the lab who were there along the way cheering me up and filling me with lovely memories. First of all, to Mayra -my “novia”- because I literally would not be here if it weren’t for you! I’m so grateful that you encouraged me -and recommended me- to start my academic life outside Colombia. I’ve learnt a lot from you, professionally and personally, and I’m very happy that our friendship has grown so much over the years. Because we always enjoy the time together either if it’s catching up, talking about science, laughing, worrying about the future, or shopping. I hope you’re back in NL very soon to continue sharing and growing together. To Vivi/Fifi/Sandris: Thank you for always being there, for encouraging me to continue through hard times, and for celebrating with great enthusiasm all my successes. I feel so happy that life brought you to our paths in such a coincidental way! I admire your determination and how selfless you always are, offering your help even for science-related things! I wish you a great new life chapter in tropical lands, that your family keeps growing happy and full of love, and that our paths cross again soon!

To my Colombian, Latin and Latin-adjacent friends: Kieucita, Ailine, Engel, Alfred,

Gaby, Lili, Marty, Paola, David, Alejo, Maria, Andres, Mago, Diego, Julio, and Genaro. You guys made me feel close to home and made me happy with all

those great times cooking, gossiping, laughing, singing, and dancing. I have great memories with all of you and I hope we get to have many more of those great times together!

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To Kieucita, Ailine and Engel, extra thanks for sharing so many great moments since our master’s. It’s been great seeing how far we've come, it’s kinda like growing together, no? :) I wish you all the best!

To my roommates over these years Yoshita, Sreejita, Ailine, Jorge, Pedro and

Marcel: thank you for all the company, help, food and great times together. George, I also want to thank you for your constant support, lovely messages and

deep conversations about professional, personal and existential topics. I hope we can continue to share many more of those for many years, no matter where we are! Marcelín, thank you for being the lovely encouraging friend you are and for accepting the task of being one of my thesis design advisors! I love that we can share so many sides together (From silly jokes, through delicious food, to serious topics) and I feel very happy that we’ve kept on sharing even after I moved out. I hope that we share even more now that we’ll be semi-neighbors.

To the Spanish club: Ana, Matt, Magda, Vera and Gosia, for all those fun moments together, Gracias! I especially would like to thank Ana for sharing this journey with me, for the lovely long lunches and dinners catching up, for the constant encouragement and for all the fun moments together.

Dani Yepes, Dani De Fex, and Laura Rueda: I’m so grateful that we have grown so

much together and that we have formed such a strong and loving support system. It’s amazing to see how close we are after so many years of friendship and despite the distance. I hope we get to make many more wonderful memories together and that our friendship keeps only moving forward through the years!

Last but not least, I want to thank my family. To all the Florez, especially Carmen,

Maqui, and Camilo, thank you for always sending me your love and celebrating

all my success. To all the Sampedro, thank you! Especially Calu, for being my fairy godmother and second mom, for all your love and thoughtful details, for giving me so many opportunities to fulfill my dreams and for creating a home away from home with my cousins/almost brothers Dani and Kiko. Growing up with you guys was wonderful and it fills me with happiness to see how far all members of DaLaFe have come (hopefully soon we'll have a full European edition of DaLaFe ;) ). Thank you, for being there to share so many adventures with me.

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To my parents and my sister, the people that know me best in the world and have offered their unconditional support, help, and love through this and all other experiences in my life. Despite the distance you are my biggest support system and personal cheerleading team. I don’t have enough words to express how much love, admiration and gratitude I have for you. Mom: thank you for also being my personal psychologist and true friend. I could not have made it to this point without your advice, deep analyses, love, and encouragement. Dad: thank you for always being willing to listen and offer advice, pointing at the positive side of life and helping me find my own inner motivation. Thank you both for always being a great example for Isa and me. You’ve shown us the meaning of dedication, aiming for excellence, learning, appreciation for music, and love for good food. Isa: thank you for bringing fun and color into our lives, for understanding and loving my sensitive side, and for teaching me about other creative and fun ways to enjoy life. I feel very happy that we’ve gotten so close over the years and that we have shared and supported each other so much. Lastly, to Tim, mi partner, my love, “mi mono”, my home. I feel so lucky to have you in my life and to be able to say that you are a true part of my family. I want to thank you for supporting me and comforting me during this challenging period of my life and for always reminding me that it’s ok to not do everything all at once and that’s important to also make time to have fun. Thank you for also bringing your family into my life because they welcomed me from day one and have made me feel like I in fact have a family away from Colombia. Marcel & Nancy: thank you for always welcoming us in your lovely home and for all the fun moments, deep conversations, and constant support, together with Daan. To Joep & Lilian: Thank you for making us feel your love and support through the distance, and for creating so many lovely memories together across the world. Lindura, we have passed hard challenges, enjoyed many adventures, and grown a lot together in this period. I hope that we get many more great adventures ahead together! ;)

Thank you all! Dank jullie allemaal! ¡Gracias a todos!

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APPENDIX

A

bout

the

Author

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About the author

Laura Florez Sampedro was born in Medellin, Colombia on October 3rd 1987. From early age she was fascinated by medical encyclopedias and wanted to learn about the human body and diseases. Ever since she has developed a strong interest in molecular immunology and cellular biology and has followed this passion through her academic path. She did a bachelor in Biology with emphasis in cellular biology at the Universidad de Antioquia, in Medellin. For her bachelor thesis she studied the antiviral effect of mushroom extracts on HIV-1 infection in vitro. Later she did two 6-month

internships at the Ohio State University, were she collaborated in the research of molecular mechanisms of cancer. She then moved to Groningen, The Netherlands for her master studies in Medical and Pharmaceutical Drug Innovation, with a 2-year scholarship from the University Medical Center Groningen. Her master internships at this medical center were focused on the study of miRNAs in COPD (1) and the immunomodulatory function of dietary fibers (2). She received her master's degree cum laude and was granted an MPDI-GRIP fellowship for her PhD at the University of Groningen. During her PhD she studied the role of the cytokine MIF in chronic lung diseases, under the supervision of Barbro Melgert and Gerrit Poelarends.

Alongside her academic path, she has been involved in artistic activities since her childhood. She was part of the dance academy Jazzdance in her hometown for around 10 years where she practiced jazz dancing, tap dancing and ballet. She has further developed her love for painting in the last years, especially for watercolor. Also, she recently entered the world of digital design, and hopes to be able to use these digital tools in the future to integrate her two passions: art and science.

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List of publications

(In chronological order of publication)

Unravelling the complexity of COPD by microRNAs: it's a small world after all. Osei ET*, Florez-Sampedro L*, Timens W, Postma DS, Heijink IH, Brandsma CA.

Eur Respir J. 2015 Sep;46(3):807-18. PMID:26250493.

*Shared first authorship

In vitro anti-HIV-1 activity of the enzymatic extract enriched with laccase produced by the fungi Ganoderma sp. and Lentinus sp.

Florez-sampedro L , Zapata W, Orozco LP, Mejía AI, Arboleda C , Rugeles MT.

Vitae vol.23 no.2 Medellín May/Aug. 2016. http://dx.doi.org/10.17533/udea.vitae.v23n2a03

miR-146a-5p plays an essential role in the aberrant epithelial-fibroblast cross-talk in COPD.

Osei ET, Florez-Sampedro L, Tasena H, Faiz A, Noordhoek JA, Timens W, Postma DS, Hackett

TL, Heijink IH, Brandsma CA.

Eur Respir J. 2017 May 25;49(5). PMID:28546273

The diversity of myeloid immune cells shaping wound repair and fibrosis in the lung.

Florez-Sampedro L, Song S, Melgert BN.

Regeneration (Oxf). 2018 Feb 23;5(1):3-25. PMID: 29721324

The role of MIF in chronic lung diseases: looking beyond inflammation.

Florez-Sampedro L, Soto-Gamez A, Poelarends GJ, Melgert BN.

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