Tim M. Townes, Ph.D.
Professor, Chair, Department of Biochemistry and Molecular Genetics
Areas of Focus: The major interest of my laboratory is the regulation of gene expression during development.
Developmental Regulation of Gene Expression: The major interest of my laboratory is the regulation of gene expression during development. We study the human hemoglobin genes as a model system and translate our understanding of basic mechanisms of globin gene regulation into strategies to correct hemoglobinopathies such as beta-thalassemia and sickle cell disease. Our work focuses on the following 4 areas: (1) Globin gene switching during development (2) Locus Control Region regulation of chromatin structure and gene expression (3) Genetic modifiers of sickle cell disease severity and (4) Gene replacement therapy using induced Pluripotent Stem (iPS) Cells.
Our goals are to define the basic mechanisms that control globin gene regulation and to use these discoveries to develop novel strategies to cure hemoglobinopathies. Most of our studies involve the production of transgenic, knockout and knockin mice that enable us to define mechanisms of globin gene regulation and disease progression in vivo. In addition, we are now deriving human iPS (induced Pluripotent Stem) cells from skin biopsies of sickle cell patients and correcting the sickle mutation either before or after iPS cell production. Our ultimate goal is to differentiate corrected iPS cells into hematopoietic stem cell for transplantation into patients.
Some of the accomplishments of my graduate students, postdoctoral fellows and collaborators are as follows:
(1) the first transgenic mice that express a correctly regulated human gene
(2) the competition model of human hemoglobin switching during development
(3) the first mice that express functional human hemoglobin A and S
(4) the first knockout mouse model of beta-thalassemia
(5) the first mouse model of sickle cell disease.
(6) the first correction of a disease utilizing iPS cells (collaboration with Jacob Hanna and Rudolf Jaenisch at MIT)
Recently, we have produced knockin mice that contain HA/FLAG tagged transcription factors to define complexes that regulate globin gene expression in vivo. We have also extended these studies to transcription factors (Oct4, Sox2 and Klf4) that direct iPS cell formation. Mass spectrometry analysis is used to define the components that are required for chromatin remodeling. In summary, our lab uses biochemical, molecular biological and mouse genetics approaches to define basic mechanisms of gene regulation and to develop strategies to correct mouse models of human genetic diseases.
Tim M. Townes (b.1951), Professor and Chairman of Biochemistry and Molecular Genetics, received his B.S degree in 1973, an M.S. degree in Zoology in 1975, and a Ph.D. degree in Microbiology in 1980 from the University of Tennessee. After completing his graduate studies, he joined Dr. Jerry Lingrel's group at the University of Cincinnati, where he studied globin gene expression in goats and transgenic mice. He joined the UAB faculty in 1984. His research is supported by grants from NIH.