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Faculty Detail    
Name THOMAS M RYAN
 
Campus Address MCLM 566 Zip 0005
Phone 205-966-2175
E-mail tryan@uab.edu
Other websites
     


Faculty Appointment(s)
Appointment Type Department Division Rank
Primary  Biochemistry & Molecular Genetics  Biochemistry & Molecular Genetics Associate Professor
Center  Civitan International Research Center  Civitan International Research Center Associate Professor
Center  Comprehensive Cancer Center  Comprehensive Cancer Center Associate Professor

Graduate Biomedical Sciences Affiliations
Biochemistry and Molecular Genetics Program 
Biochemistry and Structural Biology 
Cell, Molecular, & Developmental Biology 
Cellular and Molecular Biology Program 
Genetics and Genomic Sciences 
Medical Scientist Training Program 

Biographical Sketch 
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 the Graduate Program Director in 2004.

Research/Clinical Interest
Title
Stem Cell Therapies in Animal Models of Human Disease
Description
The research in our laboratory is focused upon understanding basic mechanisms of gene regulation in order to develop and subsequently cure animal models of human disease. Knowledge gained from our studies of the high-level, tissue-specific, and temporally regulated expression of human globin genes in transgenic mice have enabled the generation of mouse models of sickle cell disease and beta thalassemia that faithfully mimic and reproduce most if not all of the pathology of the disorders. Recently, the laboratory has published a novel preclinical humanized mouse model of Cooely's Anemia. Embryonic stem (ES) cells have multiple qualities that make them invaluable for the production of genetically modified mice. These same characteristics also make them an ideal tool for future cell based therapies. Namely, ES cells can be propagated in a pluripotent state indefinitely, genetically modified site-specifically by homologous recombination, clonally isolated, expanded to great numbers in culture, and directed to differentiate in vitro to numerous cell types. We are developing ES cell based therapies to model the correction and cure of inherited genetic disease utilizing our mouse models of beta thalassemia and sickle cell disease. ES cells derived from somatic cells of diseased mice are corrected by homologous recombination and differentiated in vitro to hematopoietic stem cells for transplantation back into the diseased animals. The long-term goals of this project are the development of therapeutic methods that are efficient, reproducible, safe, and translatable to human therapy. Consequently, the laboratory is also modeling some of these methods in human ES cell lines.

Selected Publications 
Publication PUBMEDID
Ryan, T. M., Ciavatta, D. J., and Townes, T. M. (1997) Knockout-Transgenic Mouse Model of Sickle Cell Disease, Science, 278: 873-876.  9346487 
Ryan, T. M., Behringer, R. R., Townes, T. M., Palmiter, R. D., and Brinster, R. L. (1989) High Level Erythroid Expression of Human Alpha-Globin Genes in Transgenic Mice, Proc. Natl. Acad. Sci. USA, 86, 37-41.  2911581 
Behringer, R. R., Ryan, T. M., Reilly, M. P., Asakura, T., Palmiter, R. D., Brinster, R. L., and Townes, T. M. (1989) Synthesis of Functional Human Hemoglobin in Transgenic Mice, Science, 245: 971-973.  2772649 
Ryan, T. M., Behringer, R. R., Martin, N. C., Townes, T. M., Palmiter, R. D. and Brinster, R. L. (1989) A Single Erythroid-Specific DNase I Super-hypersensitive Site Activates High Levels of Human Beta-globin Gene Expression in Transgenic Mice, Genes and Development, 3:314-323.  2721958 
Ryan, T. M., Townes, T. M., Reilly, M. P., Asakura, T., Palmiter, R. D., Brinster, R. L., and Behringer, R. R. (1990) Human Sickle Hemoglobin In Transgenic Mice, Science, 247: 566-568.  2154033 
Huo Y, McConnell SC, Liu S, Zhang T, Yang R, Ren J, Ryan TM. (2010) Humanized mouse models of Cooley's anemia: correct fetal-to-adult hemoglobin switching, disease onset, and disease pathology, Ann N Y Acad Sci., 1202:45-51.  20712771 
Huo Y, McConnell SC, Ryan TM. (2009) Preclinical transfusion-dependent humanized mouse model of beta thalassemia major, Blood, 113(19):4763-70.
 
19258591 
Huo Y, McConnell SC, Liu SR, Yang R, Zhang TT, Sun CW, Wu LC, Ryan TM. (2009) Humanized Mouse Model of Cooley's Anemia, J Biol Chem., 284(8):4889-96.
 
19098001 
Behringer, R. R., Ryan, T. M., Palmiter, R. D., Brinster, R. L., and Townes, T. M. (1990) Human AGamma- to Beta-Globin Gene Switching In Transgenic Mice, Genes and Development, 4: 380-389.  1692558 
Wu LC, Sun CW, Ryan TM, Pawlik KM, Ren J, Townes TM. (2006) Correction of sickle cell disease by homologous recombination in embryonic stem cells, Blood, 108(4):1183-8.
 
16638928 
Levasseur, D. N., Ryan, T. M., Reilly, M. P., McCune, S. L., Asakura, T., and Townes, T. M. (2004) A Recombinant Human Hemoglobin with Anti-sickling properties greater than fetal hemoglobin, J. Biol. Chem., 279(26): 27518-27524.  15084588 
Levasseur, D. N., Ryan, T. M., Pawlik, K. M., and Townes, T. M. (2003) Correction of a Mouse Model of Sickle Cell Disease: Lentiviral/Anti-Sickling Beta-globin Gene Transduction of Unmobilized, Purified Hematopoietic Stem Cells, Blood, 102: 4312-4319.  12933581  
Ryan, T. M., Sun, C.-W., and Townes, T. M. (2000) Human Gamma-globin Gene Promoter Element Regulates Human Beta-globin Gene Developmental Specificity, Nucleic Acids Res. 28:2736-2740.  10908330 

Keywords
Sickle cell anemia, thalassemia, embryonic stem cells, hemoglobin, mutagenesis, gene regulation