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Epigenetic control of retinoic acid-dependent genes during heart development

Periodic Reporting for period 1 - EPIGENHEART (Epigenetic control of retinoic acid-dependent genes during heart development)

Reporting period: 2015-07-01 to 2017-06-30

EPIGENHEART has proposed a unique and competitive program for heart development research centered on heart malformations, a leading cause of death worldwide. Defects in the pathways for the myocardial lineages can result in various congenital malformations. My main objective has been to identify the transcriptional regulatory events that underlie the localized formation of the different types of myocardium of the embryonic heart. With the use of in vitro and in vivo approaches in transgenic and deficient mouse embryos combined with transcriptomic and chromatin profiling, the interacting research lines of EPIGENHEART is fulfilling this goal. There is a very small number of lab working on cardiac development in France compared to other EU countries and US. EPIGENHEART has allowed me to develop a novel line of research with the use of concepts and combined modern methods that no group in France has approached so far for understanding heart disease. In addition to the impact on human health, the project has contributed to future career prospects, France’s scientific excellence and competitiveness on the international level. With this funding support not only for my salary but also for my training activities and expenses related to my research costs, I have been able to strengthen my scientific expertise, leadership and management skills allowing me to reach a competitive position at the National Institute of Health and Medical Research (INSERM).
Publications: Manuscripts have been published open access, ensuring they are accessible to all the scientific community and beyond. Target journals have included specialized journals for Developmental Biologists (Mechanisms of development).
Conferences: The actions that I took for communicating my research results have been through my experiences as international collaborator with both scientists and clinicians and my participation to conferences (Weinstein, European Society of Cardiology, Keystone Symposia, French Developmental Biology meetings). It has ensured the dissemination of my results to broad audiences, as these large conferences venues cut across very different disciplines of cardiovascular diseases, developmental and molecular biology, and on occasion private sector companies. As a female, dissemination of my results to broad audience is raising the profile of women in science, underscoring the advantages of promoting equal opportunities. I have been also involved in the organization of a Keystone Conference: Pr Christoffels assistant for the Keystone Symposium Heart Disease and Regeneration: Insights from Development, Colorado, USA, 2015.

I also took take part of several vulgarization events where I was able to explain and diffuse the contribution of EPIGENHEART to fundamental knowledge in biology and its major impact in understanding heart defects in patients and increasing the potential of developing novel therapeutic strategies. I specified in all my publication, publicity, including at conferences and seminars, that the project had the support of the Marie Skłodowska-Curie Individual program (IF) :
(1) Website: I completed our website during the first month of the fellowship where I explained the importance, aims and progression on the project by including photos/videos of experiments. The website also includes my publications.
2) Creation of dissemination materials: posters
3) Le goût des sciences: This project targeted the students from secondary and high school. The objective was to raise awareness of science to scholars, develop their ability to create and innovate and foster their motivation to embrace research careers.
4) Actions directed to the public at large: AFMTéléthon: Telethon is a televised fundraising event for treatment of muscular genetic diseases. The host institute U910 benefits from its support and I was involved in a workshop on communication for educating the public. (4) Journee des familles: AFM organizes each year ”day of families” in Paris and Marseille in order to also allow the families and patients to meet scientists. (6) Fête de la science: This event takes place each year in October. I participated to this national event and exposed my work to the public.

Mechanisms of retinoic acid signaling during cardiogenesis.
Stefanovic S, Zaffran S.
Mech Dev. 2017 Feb;143:9-19. doi: 10.1016/j.mod.2016.12.002. Epub 2016 Dec 19. Review.
Open access

Hoxa1 and Hoxb1 are required for pharyngeal arch artery development.
Roux M, Laforest B, Eudes N, Bertrand N, Stefanovic S, Zaffran S.
Mech Dev. 2017 Feb;143:1-8. doi: 10.1016/j.mod.2016.11.006. Epub 2016 Dec 10.
Open access

Since the work being performed takes place in a basic research department with close connections to the clinic, interchange of ideas is greatly facilitated. My results are candidates for different exploitation strategies by patents: (1) Identification of new genes which may be the base of diagnosis and prognosis kits to be developed by private companies through the dissemination of the results. (2) Development of new ES cell lines and improvements on differentiation protocols. Further translational research activities are planned after the project will finish to prove their feasibility.

This granted award has been an invaluable asset to the start of Sonia Stefanovic’s career as a young independent researcher. She successfully applied for an independent research position at National Institute of Health and Medical Research (INSERM). We strongly believe that with this funding support not only for Sonia’s salary but also for her training activities and expenses related to her research costs, she has been able to strengthen her scientific expertise, leadership and management skills allowing her to reach a competitive position at INSERM.

During these 18 months, Dr Sonia Stefanovic has proven to be an excellent addition to my research team. She is undoubtedly making an excellent work. She has independent new ideas for moving her project forward. She is creative and open to new concepts. She demonstrated that she was skilful at the bench and has been very productive. Dr Sonia Stefanovic’s experience has proven to be very complementary to my lab’s interests in mouse development. Her current work will contribute to better insight into the molecular regulatory mechanisms underlying normal and abnormal heart development, and will likely be submitted in the coming year in a high impact factor journal. I believe that Dr Sonia Stefanovic is an exceptionally bright, highly motivated and knowledgeable young scientist.

In France, doctoral student are supervised by a thesis director holding an accreditation to supervise students (“Habilitation à Diriger des Recherches”). Sonia Stefanovic’s intention is to obtain this authorization by AMU the coming months of this year.

I do think that Marie Curie actions are invaluable asset to the start of a career as a young independent researcher.