Robert E. Richard, M.D., Ph.D.

Our research group is based at the Seattle Division of the VA Puget Sound Health Care System in the Beacon Hill neighborhood.

Pathogenesis of the classic myeloproliferative disorders.  The discovery of the role of the Jak2V617F mutation in myeloproliferative disorders (MPDs) helped explain the phenotype of this class of stem cell disorder.  Previous work performed in the lab of Tony Blau demonstrated the proliferative potential of a regulatable mpl molecule in human cells to expand human erythroid precursors.  However, with other growth promoting cytokines, other cell lineages could be expanded.  We believe that the pleiotropic effects of dysregulated Jak2 signaling in the MPDs is explained by activation of other gene pathways.  Using retroviral gene transfer of the MPD mutations we intend to identify other gene pathway that play a role in MPD pathogenesis.

Stem cell gene therapy to treat advanced HIV infection.  Treatment for HIV infection are continually changing in response to the appearance of strains resistant to standard medications.  Genetically engineered immune cells derived from adult blood stem cells could help rebuild the immune systems of AIDS patients.  We have developed retrovirus vectors that can enter human blood stem cells and genetically alter the stem cells so that all cells are protected from HIV infection.  By transplanting AIDS patients with genetically modified stem cells, an immune system protected from infection can develop.

The virus vectors we have developed are based on foamy virus, a non human primate virus that has never been associated with a specific disease.  A major advantage of this vector system is its ability to make virus particles in the presence of anti-HIV genes.  This is not the case with other vector systems in development for this purpose.  In fact, when expressed in a different vector based on lentiviruses, two of the genes in our anti-HIV vector block the ability to make the vector.  We have been able to high-titer stocks of our anti-HIV vector so that a clinical trial could be performed.  The results of our studies were published in Molecular Therapy in January 2008.  We are pursuing further studies in anticipation of submitting an investigational new drug application to the Federal Drug Administration.