Joke Devoldere

Contact

Joke Devoldere

Laboratory for General Biochemistry and Physical Pharmacy
Ghent University
Ottergemsesteenweg 460
9000 Gent
Belgium
Tel: 0032 9 2648047 (secretary)
Tel: 0032 9 264 8360 (direct)

E-mail: joke.devoldere@UGent.be

Biography

Education:

2013: Master in Pharmaceutical Care at the department of Pharmaceutical Sciences, Ghent University, Belgium (Title of the master thesis: Optimization of ultrasound-induced transfection and elucidation of the sonoporation mechanism by means of confocal microscopy).

Scholarship:

Ph.D. fellowship of the Research Foundation-Flanders (FWO)

Research interests:

Non-viral gene therapy, cellular barriers, induced pluripotent stem cells, reprogramming, mRNA, intracellular innate immune system, global gene expression

Educational tasks:

Lab instructor and tutor for the Pharmaceutical Bachelor Proof since 2014 (Ghent University, Belgium)

Summary of Research Project(s)

My research project focuses on the reprogramming of fibroblasts into pluripotent stem cells by means of mRNA based non-viral gene delivery.

Joke Devoldere research project1

In 2006, Yamanaka and his co-worker made a groundbreaking discovery as they found out that pluripotent stem cells can be generated directly from human skin cells. They discovered that only 4 transcription factors need to be added to transform fibroblasts into pluripotent cells, which they called induced pluripotent stem cells (iPSCs). Although the principle of administering only 4 different transcription factors seems very simple and straightforward, since 2006, researchers keep on trying to optimize the transfection protocols in order to render safe and stable iPSCs generation. While viral transfection methods can be used for in vitro applications, the making of iPSCs for further human use is associated with risks of insertional mutagenesis. Therefore, non-viral reprogramming of iPSCs is preferred.

 

Joke Devoldere research project2


An ideal candidate to introduce protein expression in living cells is mRNA. Unlike pDNA, mRNA is translated in the cytoplasm of the cells, thus avoiding the difficulty to cross the nuclear membrane. In 2010, Warren et al demonstrated that lipid-based mRNA transfections could be used to efficiently generate iPSCs. Their reprogramming protocol, however, involved 17 daily repeated transfections, which has been shown to severely compromise cell viability, if no immunosuppression was performed. Administration of mRNA seems to activate the intracellular innate immune response, making repeated transfections over time almost impossible due to the low survival rate of the transfected fibroblasts. In this project we aim to optimize this mRNA-based reprogramming by a) increasing the time frame of mRNA expression in order to reduce the number of repeated administration, b) decreasing the needed dose of mRNA to avoid immune stimulation and c) inhibition or circumvention of the intracellular innate immune responses. Hence, a fundamental understanding of the intracellular processes which determine protein expression is needed.