Professor
Genetics, Cell Biology and Development
University of Minnesota
420 Washington Avenue SE
Minneapolis, Minnesota 55455
Room: 5-124 MCB
Phone:(612) 625-6988
Fax:(612) 626-7031
e-mail: somia001@umn.edu
Research Interests
My interests are in the development and refinement of retrovirus vectors as tools for gene therapy and gene discovery.
Our ability to transfer genes into cells is at the heart of the concept of gene therapy (Somia and Verma, 2000). The retrovirus life cycle can be subverted so that the virus will ferry therapeutic genes into cells, as opposed to its normal pathogenic cargo. Although the methods already developed are sophisticated and allow high levels of gene transfer, one of the next steps in the development of vectors is to target infections to certain cell types. This will have great utility in organs such as the brain, which is composed of a complex mix of heterogeneous cells, as well as uses in systems where the cells are dispersed through the body - such as blood. Since the present vectors infect most cell types, they also include cells such as dendritic cells - the professional antigen presenting cells of the immune system. This could generate an immune response against the vector, the therapeutic gene product or both. In this regard, targeted vectors are important in the cell types that they don't infect. Presently we are developing and refining new envelope proteins, which would mediate binding to the target cell and facilitate entry of the vector RNA in the cell (Somia et al., 1995, and Somia et. al., 2000).
More recently I have also been interested in developing these high efficiency gene transfer tools towards gene discovery. To this end we have generated cDNA libraries in retroviral vectors enabling us to transfer entire complements of coding RNA from one cell type to another. If we can devise a suitable screen for the target cell, this technology enables us to discover function for the cDNA encoded by the retroviral vector. In initial screens we focused on programmed cell death, or apoptosis, caused by a molecule called Fas. We generated a cDNA library from a cell line that is resistant to Fas mediated cell death, transferred the library into a cell line that was sensitive to Fas mediated cell death, and cloned a novel gene for a protein that confers resistance to Fas (Somia et al., 1999). We are currently dissecting this new gene and learning about its function and how it mediates the protection to apoptosis, a process that is important in development, the immune system, and in cancer. We want to expand on this technology and have a number of different screens that will allow us to clone and identify the function of genes in diverse processes such as in stem cells, in transcription and in viral infection - which connects us back to our interest in gene therapy.
Recent Publications