Neuromuscular junctions - Hannah Storrie
FULL VIEW

PREVIOUS IMAGE
NEXT IMAGE
1
8
1. Neuromuscular junctions - Hannah Storrie; 2. Fluorescent endothelial sprouting assay - Eduardo Silva; 3. SEM microscopy - Claudia Fischbach; 4. Endothelial sprouting assay - Will Yuen; 5. Histology - Eduardo Silva; 6. Histology - Eduardo Silva; 7. Cells adhering to a surface - James Cunningham; 8. SEM microscopy - Claudia Fischbach;
Lieven Thorrez
Postdoctoral Fellow
lieven_thorrez@brown.edu

Education

1995 - 2000: Bio-engineering, cell- and gene biotechnology, Ghent University (Belgium)

1998 - 1999: Exchange student University of Helsinki (Finland)
1999 - 2000: Research assistant in Center for medical genetics, Ghent (Belgium)

2000 - 2005: PhD in medical sciences, Leuven University (Belgium) Topic: Gene therapy for hemophilia A and B using different viral vectors.
2006 - current: Postdoctoral Bio-engineering fellow at Brown University (Prof. H. Vandenburgh) and Harvard University (Prof. D. Mooney)

Research Focus

My work is at the crossroads of tissue engineering, stem cell biology and gene therapy. Engineered muscle tissue is being developed as a vehicle for cell based protein delivery.
Current therapies consisting of direct protein administration often do not result in optimal benefits to patients, resulting from the inability to deliver the protein in a physiological manner. Implantable pumps for protein delivery are not currently available for long-term human use. A constant delivery of physiological levels of proteins by genetically engineered implanted cells would be advantageous in optimizing the protein effects while minimizing side effects.
Skeletal muscle cells can be genetically and tissue engineered in vitro into functional bio-artificial muscles with organized postmitotic muscle fibers towards this end. The use of implantable bio-artificial muscles would have significant advantages over currently available technologies for protein delivery: continuous administration, predictable dosage and reversibility.
Development of bio-artificial muscles to ensure a long-term protein secretion requires a multidisciplinary approach. First, different gene transfer strategies are evaluated for efficiency, safety and potential for long-term transgene expression in muscle progenitor cells. Second, the matrix wherein cells are embedded needs to be optimized to improve the viscoelastic properties for implantation into mechanically active sites. Third, strategies for an appropriate vascularization and maintenance of fiber tension are pursued to ensure an optimal cell survival and long-term protein delivery. Bio-artificial muscles have been tested extensively in mice and current efforts are geared to extend these results in a dog model.
This technology has a wide range of potential clinical applications in e.g. muscle and bone wasting, anemia, arthritis, and cardiovascular disorders.

Publications

  • VandenDriessche T, Thorrez L, Naldini L, Follenzi A, Moons L, Berneman Z, Collen D, Chuah MKL. Lentiviral vectors containing the HIV-1 central polypurine tract can efficiently transduce non-dividing hepatocytes and antigen-presenting cells in vivo. Blood 2002; 100(3):813-822.
  • Chuah MKL, Schiedner G, Thorrez L, Johnston M, Vangoidsenhoven E, Hertel S, Lillicrap D, Van Rooijen N, Collen D, VandenDriessche T, Kochanek S. Persistent therapeutic human and canine factor VIII levels and negligible toxicity in hemophilic mice following gene therapy with high-capacity adenoviral vectors. Blood 2003; 101(5):1734-43.
  • Thorrez L, VandenDriessche T, Collen D, Chuah MK. Preclinical gene therapy studies for hemophilia using adenoviral vectors. Sem. Thromb. Haem. 2004; 30(2):173-83.
  • Van Damme A*, Thorrez L*, Ma L, Vandenburgh H, Eyckmans J, DellÕAccio F, De Bari C, Luyten F, Lillicrap D, Collen D, VandenDriessche T, Chuah MK. Efficient lentiviral transduction and improved engraftment of human bone marrow mesenchymal cells. Stem Cells 2006; 24(4):896-907. (*contributed equally)
  • Thorrez L, Vandenburgh H, Callewaert N, Mertens N, Shansky J, Wang L, Arnout J, Collen D, Chuah M, VandenDriessche T. Angiogenesis enhances factor IX delivery and persistence from retrievable human bioengineered muscle implants. Molecular Therapy 2006; 14(3):442-451.
  • VandenDriessche T*, Thorrez L*, Acosta-Sanchez A, Petrus I, Wang L, Ling M, De Waele L, Iwasaki Y, Gillijns V, Wilson J, Collen D, Chuah M. Efficacy and safety of adeno-associated viral vectors based on serotype 8 and 9 versus lentiviral vectors for hemophilia B gene therapy. Journal of thrombosis and haemostasis 2006 [Epub ahead of print]. (*contributed equally)