Stem Cell Therapies in Animal Models of Human Disease. Our laboratory is focused upon understanding basic mechanisms of gene regulation in order to cure human disease. We have utilized the knowledge gained from our studies of the high-level, tissue-specific, and temporally regulated expression of human globin genes in transgenic mice to develop animal models of human hemoglobin disorders. We are testing novel genetic and stem cell therapies designed to cure humanized mouse models of sickle cell anemia and beta thalassemia major (Cooley's Anemia).
Pluripotent stem cells have multiple qualities that make them an ideal tool for future cell based therapies. Namely, pluripotent stem cells can be propagated in culture indefinitely, genetically modified, clonally isolated, expanded to great numbers in culture, and directed to differentiate in vitro to numerous cell types. We are developing pluripotent stem cell based therapies to model the correction and cure of inherited genetic disease utilizing our humanized mouse models of Cooley's and sickle cell anemias. The long-term goals of these projects are the development of therapeutic methods that are efficient, reproducible, safe, and translatable to human therapy.
Additional projects ongoing in our laboratory are mutagenesis screens in mice designed to identify genes that control the fetal to adult hemoglobin switch, genes that regulate the induction of leukemia in the erythroid lineage, and the role of hemoglobin in the differentiation, survival, and maturation of erythroid cells.
Thomas M. Ryan (b. 1956) received B.A. degrees in Biology and Chemistry from Humboldt State University (Arcata, CA, 1982). Dr. Ryan received his Ph.D. in Microbiology in 1990 from the University of Alabama at Birmingham for his studies on human globin gene expression, synthesis, and switching in transgenic mice. These studies defined the functional importance of regulatory sequences in the locus control region of the human beta globin locus. Linkage of these sequences to the human alpha, gamma, and beta globin genes enabled the production of the first transgenic animals that synthesized functional human hemoglobin and the first demonstration of human fetal to adult hemoglobin switching. Post-doctoral research (1991-96) in the Biochemistry Department at the University of Alabama at Birmingham in the laboratory of Tim Townes led to the development of the first animal models of beta thalassemia and sickle cell disease. Continuing these studies in the Biochemistry and Molecular Genetics Department as a Research Assistant Professor (1997-2003), Dr. Ryan produced the first knockout-transgenic animal model of sickle cell disease. Dr. Ryan became an Assistant Professor in Biochemistry and Molecular Genetics in 2003 and served as the Graduate Program Director from 2004 to 2007. Dr. Ryan's laboratory is currently working on experimental stem cell therapies for human disease with a focus on Cooley's Anemia.