PhD researcher to study histone modifications in joint health and osteoarthritis

The laboratory for Tissue Homeostasis and Disease directed by Prof. Silvia Monteagudo and Prof. Rik Lories within the Skeletal Biology and Engineering Research Centre (KU Leuven) is seeking a PhD researcher candidate to study the role of histone modifications in the transition from healthy to osteoarthritic cartilage.

The Tissue Homeostatis and Disease research group:
We are an international, young and dynamic team performing cutting-edge molecular biology research in cartilage and osteoarthritis, the most common chronic joint disease worldwide. We exploit primary human cells and tissues from healthy and osteoarthritic joints, a wide array of molecular biology and multi-omics technologies, mouse models and genetic engineering, to gain groundbreaking insights into the mechanisms that control joint homeostasis and disease. Our work is published in high-profile journals such as Science Translational Medicine, Nature Communications, PNAS and Nature Reviews Rheumatology. We have strong international recognition.

Selected publications
1. Monteagudo S., Cornelis F. M. F., Aznar-Lopez C., Yibmantasiri P., Guns L-A., Carmeliet P., Cailotto F., Lories R.J. DOT1L safeguards cartilage homeostasis and protects against osteoarthritis. Nature Communications, 2017, 8, 15889.
2. Cornelis F.M.F., Monteagudo S., Guns L-A, den Hollander W., Peeters T., Storms L., Meulenbelt I., Lories R.J. ANP32A regulates ATM expression and prevents oxidative stress in cartilage, brain and bone. Science Translational Medicine, 2018, 10, eaar8426.
3. De Roover A., Núñez A.E., Cornelis F.M., Cherifi C., Casas-Fraile L., Sermon A., Cailotto F., Lories R.J., Monteagudo S. Hypoxia induces DOT1L in articular cartilage to protect against osteoarthritis. JCI Insight, 202, 6:e150451.
4. Assi R., Cherifi C., Cornelis F.M.F., Zhou Q., Storms L., Pazmino S., Coutinho de Almeida R., Meulenbelt I., Lories R.J., Monteagudo S. Inhibition of KDM7A/B histone demethylases restores H3K79 methylation and protects against osteoarthritis.

The Skeletal Biology and Engineering Research Centre at KU Leuven
The Skeletal Biology and Engineering (SBE) Research Centre, located on the Campus Gasthuisberg of the University of Leuven, contributes to a better understanding of the biology that underlies musculoskeletal diseases with the ultimate goal to develop more effective and specific therapies. The SBE is currently composed of more than 60 scientists in 4 independent research groups. We foster close collaborations with in silico modelling and with tissue engineering experts, thereby establishing a strong multidisciplinary environment.

Project

The complex relationship between epigenetic histone modifications and osteoarthritis (OA) calls for a deeper understanding of histone modifications in healthy and OA-afflicted cartilage. Previous work form our team highlight the key role of histone methyltransferase DOT1L as modulator of Wnt signaling in the disease. However, despite these insights, the precise role of other histone modifications and their interactions in the pathological process from a healthy towards an osteoarthritic joint remain elusive. By performing extensive screens and introducing state-of-the-art technologies such as EpiTOF we identify novel epigenetic factors with likely roles in the disease process. Understanding the mechanisms associated with these histone modifications could unveil novel therapeutic targets, ultimately alleviating OA burden and enhancing patient outcomes.

Profile

• You have an excellent academic record and hold a Master's degree in any area of biology or biomedical sciences. Candidates who have not yet completed their master's thesis at the time of this application are encouraged to apply.
• Previous laboratory hands-on experience with cell culture and biochemical assays is desired, but not essential. Experience with laboratory animals  and holding a Felasa B certificate is also a plus.
• You are a proactive, ambitious, dynamic person and show spirit for initiative and problem-solving. You take great care and precision in your work, and are able to work independently but also as part of a team.
• You have excellent oral and written communication skills in English.

Offer

• A full-time PhD research contract for one year with the possibility to extend (at least) 3 more years thereafter. The position is immediately available. You are stimulated to apply for a predoctoral fellowship.
• The opportunity to work on a high impact, beyond state-of-the-art project with experienced mentors in a successful team. 
• We support PhD students with excellent (daily) guidance and training, and provide the opportunity to participate in (inter)national collaborations and conferences.
• A stimulating international, multidisciplinary and dynamic research environment where quality, professionalism and collaborative team spirit are encouraged.

Interested?

For more information please contact Prof. dr. Rik Lories, tel.: +32 16 37 26 73, mail: rik.lories@kuleuven.be or Prof. dr. Silvia Monteagudo, tel.: +32 16 37 27 34, mail: silvia.monteagudo@kuleuven.be.

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