Richard Mulligan,Ph.D.


Mallinckrodt Professor of Genetics

Harvard Gene Therapy Initiative Rm 407
4 Blackfan Circle
Boston, MA 02115
Tel: (617) 432-1465
Fax: (617) 432-6146
e-mail: mulligan@receptor.med.harvard.edu
11 postdoctoral fellows, 2 graduate students


Our laboratory is primarily interested in the development of methods for the efficient transfer of genes into mammalian cells and the application of those methods to a number of problems in cell biology, developmental biology, virology and medicine. For most of our studies, we rely heavily on the use of retroviral mediated gene transfer, a powerful technology developed in our lab and others over the past ten years which makes possible the highly efficient transfer of genes into a wide variety of mammalian cells both in vitro and in vivo. Work continues on the development of retroviral vectors, particularly to develop safer packaging cell lines for the production of recombinant viruses, to develop vectors which are able to transduce non-dividing cells, and to develop vectors in which gene expression can be manipulated through the use of exogenously administered small molecules. In addition to work with retroviral vectors, we have recently initiated efforts to evaluate, in a comparative fashion, a variety of different existing methods for transferring genes into mammalian cells, including adenoviral vectors and AAV vectors, and to develop novel new vector systems, based on the use of biodegradable polymers or RNA viruses.

 

The study of hematopoiesis remains a major focus of interest in the laboratory. We are most interested in understanding the functional properties of the hematopoietic stem cell, a pluripotent cell which serves to replenish blood cells over the lifetime of an organism. The framework for our studies in this area has been the development of methods for the efficient genetic modification of stem cells. Current efforts focus primarily on the purification and functional characterization of stem cells, development of methods for the separation of quiescent and naturally replicating stem cells, and studies of the functional properties of different purified cell populations (e.g. the ability of the cells to reconstitute conditioned recipients, to respond to specific combinations of growth factors, and to be genetically modified). We also have an active program to evaluate the feasibility of different gene therapy strategies for the treatment of specific iinherited diseases involving hematopoietic cells.

 

A second major focus of the laboratory is the use of gene transfer to manipulate immune responses in different ways. One major effort is aimed at the development of novel therapeutic vaccination strategies for the treatment of cancer and AIDS, which involve either the use of genetically modified tumor cells or antigen presenting cells engineered to co-express tumor or viral antigens and specific immunostimulatory gene products. A second effort is devoted to the development of strategies to prevent the rejection of mis-matched cell or organ transplants and to more efficiently treat auto-immune disease. A new area of study that has recently been initiated in the lab involves efforts to apply gene transfer techniques towards the development of anti-cancer therapies which target the tumor vasculature.

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Immunology webpage updated 12/02/2009