Florence van Tienen, PhD
PO Box 5800
6202 AZ Maastricht
After completing her master Biomedical Sciences at the Free University in Amsterdam, Florence started in August 2005 her PhD project 'Deciphering mitochondrial and molecular pathology in Type 2 Diabetes Mellitus' under supervision of prof. Bert Smeets at the department of Genetics and Cell Biology of Maasticht University, which she completed in February 2011.
Myogenic stem cell therapy
Mitochondria are the cell energy factories that harbor their own mitochondrial DNA (mtDNA). A mutation in this mtDNA can lead to muscle weakness and exercise intolerance, for which currently no treatment is available. We are developing a myogenic stem cell therapy using the patient’s own muscle stem cells that do not contain the mtDNA mutation. Using this approach we aim to safely induce muscle regeneration and mitochondrial functioning to combat mitochondrial myopathy.
Next-generation sequencing has drastically enhanced the identification of genetic variants. However, assessment of their pathogenicity and exploring the disease-mechanism is often a challenge. To enable functional analysis of (cardio)myocytes from patients with a nuclear or mitochondrial DNA mutation, we implemented the induced pluripotent stem cell (iPSC) technology in our lab. This setup enables us to generate patient-specific iPSC-derived cardiomyocytes for analysis of e.g. their sarcomere structure and electrophysiology and study the functional effect of different levels of mtDNA mutation load within the same nuclear background in iPSCs and iPSC-derived cell-types.
Prof. Bert Smeets (co-investigator), René de Coo (co-investigator), Arthur van den Wijngaard (co-investigator), Romy Lutgens (PhD student), Ruby Zelissen (master student), Erika Timmer (research technician).
The project aimed at developing an autologous myogenic cell therapy for mtDNA mutation carriers is being funded by grants from ZonMW (Translational Adult Stem cell program), Matakids, Ride4Kids and the United Mitochondrial Disease Foundation (UMDF).
Claes, G.R., van Tienen, F.H., Lindsey, P., Krapels, I.P., Helderman-van den Enden, A.T., Hoos, M.B., Barrois, Y.E., Janssen, J.W., Paulussen, A.D., Sels, J.E. et al. (2015) Hypertrophic remodelling in cardiac regulatory myosin light chain (MYL2) founder mutation carriers. European heart journal, in press.
Costamagna, D., Quattrocelli, M., van Tienen, F., Umans, L., de Coo, I.F., Zwijsen, A., Huylebroeck, D. and Sampaolesi, M. (2015) Smad1/5/8 are myogenic regulators of murine and human mesoangioblasts. Journal of molecular cell biology, in press.
Sallevelt, S.C., Dreesen, J.C., Drusedau, M., Spierts, S., Coonen, E., van Tienen, F.H., van Golde, R.J., de Coo, I.F., Geraedts, J.P., de Die-Smulders, C.E. et al. (2013) Preimplantation genetic diagnosis in mitochondrial DNA disorders: challenge and success. J Med Genet, 50, 125-132.
van Tienen, F.H., Praet, S.F., de Feyter, H.M., van den Broek, N.M., Lindsey, P.J., Schoonderwoerd, K.G., de Coo, I.F., Nicolay, K., Prompers, J.J., Smeets, H.J. et al. (2012) Physical activity is the key determinant of skeletal muscle mitochondrial function in type 2 diabetes. The Journal of clinical endocrinology and metabolism, 97, 3261-3269.
van Tienen, F.H., van der Kallen, C.J., Lindsey, P.J., Wanders, R.J., van Greevenbroek, M.M. and Smeets, H.J. (2011) Preadipocytes of type 2 diabetes subjects display an intrinsic gene expression profile of decreased differentiation capacity. International journal of obesity, 35, 1154-1164.
van Tienen, F.H., Lindsey, P.J., van der Kallen, C.J. and Smeets, H.J. (2010) Prolonged Nrf1 overexpression triggers adipocyte inflammation and insulin resistance. Journal of cellular biochemistry, 111, 1575-1585.
van Tienen, F.H., Laeremans, H., van der Kallen, C.J. and Smeets, H.J. (2009) Wnt5b stimulates adipogenesis by activating PPARgamma, and inhibiting the beta-catenin dependent Wnt signaling pathway together with Wnt5a. Biochem Biophys Res Commun, 387, 207-211.