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Faculty Detail    
Name TIM M TOWNES
  
Campus Address SHEL 707 Zip 2182
Phone  (205) 934-5294
E-mail  ttownes@uab.edu
Other websites
     


Faculty Appointment(s)
Appointment Type Department Division Rank
Primary  Biochemistry & Molecular Genetics  Biochemistry & Molecular Genetics Professor Emeritus

Graduate Biomedical Sciences Affiliations
Biochemistry and Molecular Genetics Program 
Biochemistry and Structural Biology 
Cellular and Molecular Biology Program 
Hughes Med-Grad Fellowship Program 
Medical Scientist Training Program 

Biographical Sketch 
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.



Research/Clinical Interest
Title
Developmental Regulation of Gene Expression
Description
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) Genetic therapies to correct beta-thalassemia and sickle cell disease. 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. 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. Recently, we have produced knockin mice that contain TAP (Tandem Affinity Purification) tagged transcription factors to define complexes that regulate globin gene expression in vivo. We are also extending these studies to transcription factors that regulate other genes as part of a proteomics program to define protein:protein interactions. Mass spectrometry analysis and X-ray crystallography are utilized to define these structures. 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.

Selected Publications 
Publication PUBMEDID
Chen WY, Townes TM. Molecular mechanism for silencing virally transduced genes involves histone deacetylation and chromatin condensation. Proc Natl Acad Sci U S A. 2000 Jan 4;97(1):377-82.  10618426 
Ryan TM, Sun CW, Ren J, Townes TM. Human gamma-globin gene promoter element regulates human beta-globin gene developmental specificity. Nucleic Acids Res. 2000 Jul 15;28(14):2736-40.  10908330 
Chen W, Wu X, Levasseur DN, Liu H, Lai L, Kappes JC, Townes TM. Lentiviral vector transduction of hematopoietic stem cells that mediate long-term reconstitution of lethally irradiated mice. Stem Cells. 2000;18(5):352-9.  11007919 
Pandya K, Donze D, Townes TM. Novel transactivation domain in erythroid Kruppel-like factor (EKLF). J Biol Chem. 2001 Mar 16;276(11):8239-43.  11092887 
Divoky V, Liu Z, Ryan TM, Prchal JF, Townes TM, Prchal JT. Mouse model of congenital polycythemia: Homologous replacement of murine gene by mutant human erythropoietin receptor gene. Proc Natl Acad Sci U S A. 2001 Jan 30;98(3):986-91.  11158582 
Aslan M, Ryan TM, Adler B, Townes TM, Parks DA, Thompson JA, Tousson A, Gladwin MT, Patel RP, Tarpey MM, Batinic-Haberle I, White CR, Freeman BA. Oxygen radical inhibition of nitric oxide-dependent vascular function in sickle cell disease. Proc Natl Acad Sci U S A. 2001 Dec 18;98(26):15215-20.  11752464 
Masuoka HC, Townes TM. Targeted disruption of the activating transcription factor 4 gene results in severe fetal anemia in mice. Blood. 2002 Feb 1;99(3):736-45.  11806972 
Pandya K, Townes TM. Basic residues within the Kruppel zinc finger DNA binding domains are the critical nuclear localization determinants of EKLF/KLF-1. J Biol Chem. 2002 May 3;277(18):16304-12.  11844803 
Bradley MB, Sattler RM, Raftopoulos H, Ward M, Grossman IR, Townes TM, Ryan TA, Bank A. Correction of phenotype in a thalassemia mouse model using a nonmyeloablative marrow transplantation regimen. Biol Blood Marrow Transplant. 2002;8(8):453-61.  12234171 
Aslan M, Ryan TM, Townes TM, Coward L, Kirk MC, Barnes S, Alexander CB, Rosenfeld SS, Freeman BA. Nitric oxide-dependent generation of reactive species in sickle cell disease. Actin tyrosine induces defective cytoskeletal polymerization. J Biol Chem. 2003 Feb 7;278(6):4194-204.  12401783