I see patients with general hematological disorders at the VA on
Tuesday afternoons. I have a clinical interest in
myeloproliferative disorders and other bone marrow disorders of the
elderly. In collaboration with Bill Hobbs of the Puget Sound
Blood Center, I run an Adult Sickle Cell Clinic at the Seattle Cancer
Care Alliance on the third Thursday afternoon of the month.
CURRENT RESEARCH INTERESTS
in novel methods in gene and cell therapy.
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
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
Richard RE, Wood B, Zeng H, Jin L, Papayannopoulou T, and Blau CA: Expansion of genetically modified primary human hemopoietic cells using chemical inducers of dimerization.
Blood 95:430-6, 2000.
Richard RE, and Blau C: Small molecule directed Mpl signaling can complement growth factors to selectively expand genetically modified cord blood cells.
Stem Cells 21:71-8, 2003.
Richard RE, Weinreich M, Chang KH, Ieremia J, Stevenson MM, Blau CA: Modulating erythrocyte chimerism in a mouse model of pyruvate kinase deficiency.
Blood 103::4432-39, 2004.
Richard RE, de Claro RA, Chien S, Kiem HP, Clackson T, Andrews R, and Blau CA: CID-mediated in vivo selection: heterogeneity among large animal models.
Molecular Therapy, 10(4):730-40, 2004.
Taylor JA, Vojtech L, Bahner I, Kohn DB, Laer DV, Russell DW, and Richard
RE: Foamy virus vectors expressing anti-HIV transgenes
efficiently block HIV-1 replication. Mol. Ther. 16:46-51,