Department of Gene Therapy and Regenerative Medicine (GTRM)
Scientific rational research program
It is widely anticipated that improved gene therapy approaches will yield new treatments and cures for hereditary, acquired and complex diseases. Convincing evidence continues to emerge from clinical trials that gene therapy is yielding therapeutic effects in patients suffering from a wide range of diseases. It is therefore essential to continue to invest in gene and cell therapy to address some of the outstanding questions and overcome the remaining challenges.
Research vision and objectives
Applied translational research:
- To develop and validate gene and cell therapy for major health- and life-threatening diseases.
- To understand the molecular, cellular and immune mechanisms that influence the outcome of different gene/cell therapy approaches.
- To conduct translational gene therapy studies in large animal models in anticipation of moving forward to the clinic and initiate phase I clinical trials.
Hypothesis-driven fundamental research:
- To unravel the molecular mechanisms and pathways underlying various (patho)physiologic processes important in human health and disease.
- To consolidate a broad state of the art technology platform based on the latest viral vectors (retroviral, lentiviral, AAV), non-viral vectors (PB and SB transposons), genome engineering systems (designer nucleases -TALEN) and stem cell technologies (iPS).
The main focus of our current research program in molecular medicine is to apply this conceptual framework in the context of genetic disorders, in particular hemophilia A & B , Duchenne muscular dystrophy and myotonic dystrophy. In addition, some research activities relate to cancer in association with the VUB Oncology Research Center
Prof. Dr. Thierry VandenDriessche - Research group Director
Prof. Dr. Marinee Chuah - Research group Co-Director
Dr. Janka Matrai (PhD) - Post-doctoral fellow
Dr. Melvin Rincon (MD) - PhD student
Dr. Kshitiz Singh (MD) - PhD student
Mariana Loperfido (MSc) - PhD student
Mario Di Matteo (MSc) - PhD student
Sumitava Dastidar (MSc)- PhD student
Nisha Nair (MSc)- PhD student
Shilpita Sarcar (MSc)- PhD student
Ermira Samara-Kuko (MSc)- Research assistant
Brenda Amondi - MSc student
Jessica Willems - MSc student
Omid Ghandeharian - MSc student
Hui Wang - PhD student (pending)
In chronological order - Scientific output consists of about 100 publications with nearly 3000 citations. Selected publications are shown (IF >10 papers are indicated with *).
- *VandenDriessche et al. Long-term expression of human coagulation factor VIII and correction of hemophilia A after in
vivo retroviral gene transfer in factor VIII-deficient mice. Proc. Natl. Acad. Sci. USA 18 (96): 10379-10384 (1999).
- *Carmeliet et al. Synergism between vascular endothelial growth factor and placental growth factor contributes to
angiogenesis and plasma extravasation in pathological conditions. Nat Med. 7(5):575-83 (2001).
- *VandenDriessche, et al. Lentiviral vectors containing the HIV-1 central polypurine tract can efficiently transduce nondividing
hepatocytes and antigen-presenting cells in vivo. Blood 100 (3): 813-822 (2002).
- *Chuah et al. Therapeutic factor VIII levels and negligible toxicity in mouse and dog models of hemophilia A following
gene therapy with high-capacity adenoviral vectors. Blood 101(5):1734-1743 (2003).
- *Yamada et al. Nanoparticles for the delivery of genes and drug into hepatocytes. Nat. Biotech. 21(8):885-890 (2003).
- *De Meyer et al; Phenotypic correction of von Willebrand disease type 3 blood-derived endothelial cells with lentiviral
vectors expressing von Willebrand factor. Blood 107(12):4728-36 (2006).
- *Aragones et al. Deficiency or inhibition of oxygen sensor Phd1 induces hypoxia tolerance by reprogramming basal
metabolism. Nat. Genet., 40(2):170-80 (2008).
- *Mates, Chuah et al. Molecular Evolution of a novel hyperactive Sleeping Beauty transposase enables robust stable gene
transfer in vertebrates. Nat. Genet., 1(6):753-61 (2009).
- *Bossuyt et al. Atonal homolog 1 is a tumor suppressor gene. Plos Biol.7(2):e39 (2009).
- *Matsui et al. A murine model for induction of long-term immunologic tolerance to factor VIII does not require persistent
detectable levels of plasma factor VIII and involves contributions from Foxp3+ T regulatory cells and IL-10. Blood, 114(3):677-85 (2009).
- *Swinnen et al. The absence of thrombospondin-2 causes age-related dilated cardiomyopathy. Circulation, 120(16):1585-
- *VandenDriessche et al. Emerging potential of transposons for gene therapy and generation of induced pluripotent stem
cells. Blood, 114(8):1461-8 (2009).
- *Schneider et al. Challenges with Advanced Therapy Medicinal Products and how to meet them: The European
Committee for Advanced Therapies (CAT). Nat. Rev. Drug Disc.,9(3): 195-201 (2010).
- *Dubois et al. Differential effects of progenitor cell populations on myocardial neovascularization and left ventricular
remodeling after myocardial infarction. J. Am. Coll. Cardiol., 55(20):2232-43 (2010).
- *Ward et al. Correction of murine hemophilia A using enhanced human factor VIII cDNAs encoding various B-domain
variants. Blood, 117(3):798-807 (2010).
- Belay et al. Novel hyperactive transposons for genetic modification of induced pluripotent and adult stem cells: a nonviral paradigm
for coaxed differentiation. Stem Cells. 28(10):1760-71 (2010).
- *Matrai et al. Hepatocyte-targeted expression by integrase-defective lentiviral vectors induces transgene-specific immune tolerance
with low genotoxic risk. Hepatology, 53(5):1696-1707 (2011).
- Quattrocelli et al. Intrinsic cell memory reinforces myogenic commitment of pericyte-derived iPSCs. J. Pathol. 223(5):593-603 (2011).
Prof. Dr. Thierry VandenDriessche
Prof. Dr. Marinee K.L. Chuah
Free University of Brussels (VUB)
Faculty of Medicine & Pharmacy
Department of Gene Therapy & Regenerative Medicine
Building D - 3rd floor
B-1090 Brussels (Jette)
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