Molecular Cell Biology and Gene Therapy Science

1. Gene and Cell therapy. This research program is related to the development of new gene medicines mainly based on synthetic oligo-nucleotides (ONs). ONs are short pieces of genetic material, which can be synthesized in the laboratory. When synthesized with different chemical modifications, the ONs can obtain novel properties. Our research aims at developing molecules that can specifically turn off a gene, or correct the production of a miss-spliced mRNA. We have also developed a nano-module, which has the capacity to direct the transport of nucleic acid molecules into the nucleus in the cell.

The research also involves studies on the cellular uptake of gene medicines. Besides different chemical formulations we are also developing a new technology involving exosomes. These small vesicles that are released from multivesicular bodies from most, if not all, cells can be used as transport entities. The exosomes can be tailored to carry different drugs and designed to target the tissue of interest. Exosome composition and functional properties are also being characterized to uncover their potential for molecular therapies of the future.

Our main target diseases are inherited, namely the immunodeficiency X-linked agammaglobulinemia (XLA), the neurodegenerative Huntington’s disease, spinal muscular atrophy (SMA) and Duchenne muscular dystrophy (DMD).

2. Cell signaling in lymphocytes. Cells constantly receive signals from the outer world and such information is transferred through receptors and via biochemical pathways into the nucleus. We are studying several of the proteins involved and are in particular interested in enzymes, such as the cytoplasmic tyrosine kinase BTK. The absence of BTK causes the disease XLA (X-linked agammaglobulinemia) characterized by a total lack of B lymphocytes and antibody production, leading to a severely increased susceptibility to infections. The aim is to understand how signals are transmitted and to study the components involved. This basic knowledge is also important to pave the way for future development of treatments for diseases caused by signaling defects.

Another part of this project is related to cancer. In a certain form of T-lymphocyte tumors a chromosomal translocation creates a fusion-protein between the kinase ITK belonging to the same enzyme family as BTK, and the SYK protein. Moreover, BTK inhibitors (such as ibrutinib) are potential drugs for B cell derived tumors and we have initiated a study on their mechanism of action in both normal and malignant B cells.

Research group leaders