Richard C. Mulligan

Department of Genetics
HIM Building, Room 407
4 Blackfan Circle
Boston, MA 02115
Tel: (617) 432-1465
Fax: (617) 432-6146
Email: mulligan@receptorl.med.harvard.edu
6 postdoctoral fellows

Our laboratory continues to be primarily interested in the development of new gene and cell-based strategies for treating inherited and acquired diseases. One important goal of our current efforts in the area of vector development is to design ‘safer’ lentiviral and retroviral vectors that will prevent the serious adverse events secondary to proviral insertional mutagenesis that have been recently observed in several clinical gene therapy studies. Efforts in this area include the development of improved stable ‘packaging’ cell lines for the production of recombinant lentiviral vectors that reduce the chance of the production of replication-competent virus, the evaluation of new strategies for conditionally ablating transduced cells, and the development of a broadly applicable method for controlling vector mediated gene expression which relies on the modulation of RNA self-cleavage. This latter technology is particularly exciting in that it should enable the ability to ‘tailor’ gene control systems that respond to any small molecule drug, a capability that should have broad application in both the gene therapy field and the emerging field of biological ‘sensing’. A second major ongoing research effort in the laboratory focuses on the development of a highly efficient non-viral method for achieving ‘gene repair’ which involves the stimulation of homologous recombination at the site of a mutation via the use of ‘custom-made’ restriction endonucleases able to recognize specific DNA sequences in a genome specific fashion. Lastly, the lab has recently become interested in the development of new cell transplantation strategies for the treatment of inherited and acquired diseases which rely on the use of gene transfer to ‘engineer’ cell-cell fusion in vivo, a capability which should enable the systemic delivery of genetically modified nuclei to cells within different tissues and organs of the body.

References:

Yen, L., Svendsen, J., Lee, J.S., Gray, J.T., Magnier, M., Baba, T., D’Amato, R.J., and Mulligan, R.C. 2004. Exogenous control of mammalian gene expression through modulation of RNA self-cleavage. Nature 431: 471-476.
Murphy, G.J., Mostoslavsky, G., Kotton, D.N., Mulligan, R.C. 2006. Exogenous control of mammalian gene expression via modulation of translational termination. Nature Medicine 12: 1093-1099.
Yen, L., Stockwell, B.R., Mulligan, R.C., 2009. A mammalian cell-based assay for screening inhibitors of RNA cleavage. Methods Mol. Biol. 540: 335-347.
Bullain, S.S., Sahin, A., Szentirmai, O., Sanchez, C., Lin, N., Baratta, E., Waterman, P., Weissleder, R., Mulligan, R.C. and Carter, B.S. 2009. Genetically engineered T cells to tart EGFRvIII expressing glioblastoma. J. Neurooncol. 94: 373-382.

BBS webpage updated 6/14/2010