BIOGRAPHICAL SKETCH Provide the following information for the key personnel and other significant contributors. Follow this format for each person. DO NOT EXCEED FOUR PAGES.
NAME Thomas Alexander Cooper	POSITION TITLE Professor
eRA COMMONS USER NAME tcooper
EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, and include postdoctoral training.)
INSTITUTION AND LOCATION	DEGREE (if applicable)	YEAR(s)	FIELD OF STUDY
Moravian College, Bethlehem, PA	B.S.	1977	Biology
Temple University Medical School, Philadelphia, PA	M.D.	1982	Medicine

A. Positions and Honors.

Positions and Employment

1982-1986: Postdoctoral Fellow, laboratory of Dr. Charles P. Ordahl, Department of Anatomy, University of California, San Francisco, CA

1986-1989: Assistant Research Anatomist, Department of Anatomy, University of California, San Francisco, CA

1989-1997: Assistant Professor, Department of Pathology (primary appointment), Baylor College of Medicine, Houston, TX

1990-present: Assistant Professor, Department of Molecular and Cellular Biology (joint appointment), Baylor College of Medicine, Houston, TX

1997-2003: Associate Professor, Department of Pathology, Baylor College of Medicine, Houston, TX

2003-present Professor, Department of Pathology, Baylor College of Medicine, Houston, TX

2004-present Professor, Department of Molecular and Cellular Biology (joint appointment), Baylor College of Medicine, Houston, TX

Honors and Awards:

1981: NIH Medical Research Trainee Predoctoral Award

1982-1985: NIH Postdoctoral Fellowship

1985-1986: Bank of America Giannini Foundation Postdoctoral Award

1991-1994: March of Dimes Basil O’Connor Starter Scholar Research Award

1992-1997: Established Investigator, American Heart Association

1999 Michael E. DeBakey, M.D. Excellence in Research Award

2003 S. Donald Greenberg Chair in Pathology

B. Selected peer-reviewed publications in chronological order (of 71 total).

1. Ordahl, C.P., Cooper, T.A. (1983). Strong homology in promoter and 3’-untranslated regions of chick and rat a-actin genes. Nature 303, 348-349.

2. Cooper, T.A. and Ordahl, C.P. (1984). A single troponin T gene is governed by two different regulatory programs in cardiac and skeletal muscle development. Science 226, 979-982.

3. Cooper, T.A. and Ordahl, C.P. (1985). A single cardiac troponin T gene generates embryonic and adult isoforms via developmentally regulated alternate splicing. J. Biol. Chem. 260, 11140-11148.

4. Ordahl, C.P., Evans, G.L., Cooper, T.A., Kunz, G., Perriard, J.C. (1985). Complete amino acid sequence of chick muscle creatine kinase. J. Biol. Chem. 259, 15224-15231.

5. Cooper, T.A., Cardone, M.H., and Ordahl, C.P. (1988). Cis requirements for alternative splicing of the cardiac troponin T pre-mRNA. Nucl. Acids Res. 16, 8443-8465.

6. Cooper, T.A. and Ordahl, C.P. (1989). Nucleotide substitutions within the cardiac troponin T alternative exon disrupt pre-mRNA alternative splicing. Nucl. Acids Res.17, 7905-7921.

7. Cooper, T.A. (1992). In vitro splicing of cardiac troponin T precursors: exon mutations disrupt splicing of the upstream intron. J. Biol. Chem. 267, 5330-5338.

8. Xu, R., Teng, J., and Cooper, T.A. (1993). The cardiac troponin T alternative exon contains a novel purine-rich positive splicing element. Mol. Cell. Biol. 13, 3660-3674.

9. Lee, A.B., and Cooper, T.A. (1995). An improved direct PCR screen of bacterial colonies. BioTechniques 18, 225-226.

10. Humphrey, M.B., Bryan, J., Cooper, T.A., and Berget, S.M. (1995). A 32 nucleotide exon splicing enhancer regulates usage of competing 5’ splice sites in a differential internal exon. Mol. Cell. Biol. 15, 3979-3988.

11. Ramchatesingh, J., Zahler, A.M., Neugebauer, K.M., Roth, M.B., and Cooper, T.A. (1995). A subset of SR proteins activates splicing of the cardiac troponin T alternative exon by direct interactions with an exonic enhancer. Mol. Cell. Biol. 15, 4898-4907.

12. Ryan, K.J. and Cooper, T.A. (1996) Muscle-specific splicing enhancers regulate inclusion of the cardiac troponin T alternative exon in embryonic skeletal muscle. Mol. Cell. Biol. 16, 4014-4023.

13. Coulter, L., Landree, M., and Cooper, T.A. (1997) Identification of a new class of exonic splicing enhancers by in vivo selection. Mol. Cell. Biol. 17, 2143-2150.

14. Elrick, L.L., Humphrey, M.B., Cooper, T.A., and Berget, S.M. (1998) A short sequence within two purine-rich enhancers determines 5' splice site specificity. Mol. Cell. Biol. 18, 343-352.

15. Philips, A.V., Timchenko, L.T., and Cooper, T.A. (1998) Disruption of splicing regulated by a CUG-binding protein in myotonic dystrophy. Science 280, 737-741, also see accompanying "Perspectives" in same issue.

16. Cooper, T.A. (1998) Muscle-specific splicing of a heterologous exon mediated by a single muscle-specific splicing enhancer from the cardiac troponin T gene. Mol. Cell. Biol. 18, 4519-4525.

17. Stoss, O., Cooper, T.A., and Stamm, S. (1999) Alternative splicing determines the intracellular localization of the muscle specific nucleolar proteins NOP30-1 and NOP30-2. J. Biol. Chem. 274, 10951-10962.

18. Stark, J.M., Cooper, T.A., Roth M.B. (1999) The relative strengths of SR protein-mediated associations of alternative and constitutive exons can influence alternative splicing. J. Biol. Chem. 274, 29838-29842.

19. The International Myotonic Dystrophy Consortium (IDMC) (2000) New nomenclature and DNA testing guidelines for myotonic dystrophy type 1 (DM1). Neurology 54, 1218-1221.

20. Ryan, K.J., Charlet-B., N., and Cooper, T.A. (2000) Binding of purH to a muscle-specific splicing enhancer correlates with exon inclusion in vivo. J. Biol. Chem. 275, 20618-20626.

21. Ladd, A.N., Charlet-B., N., and Cooper, T.A. (2001) The CELF family of RNA binding proteins is implicated in cell-specific and developmentally regulated alternative splicing Mol. Cell. Biol. 21, 1285-1296.

22. Stickeler, E., Fraser, S.D., Honig^, A., Chen, A.L., Berget, S.M. and Cooper, T.A. (2001) The RNA binding protein YB-1 recognizes A/C-rich exon enhancers and stimulates splicing of the CD44 alternative exon v4. EMBO J. 20, 3821-3830.

23. Savkur, R., Philips, A.V., and Cooper, T.A. (2001) Aberrant regulation of insulin receptor alternative splicing is associated with insulin resistance in myotonic dystrophy. Nat Genet. 29, 40-47.

24. Charlet-B., Singh, G, N., Logan, P.E., and Cooper, T.A. (2002) Dynamic antagonism between CELF proteins and PTB regulate splicing of a muscle-specific exon in both muscle and nonmuscle cells. Mol. Cell 9, 649-658.

25. Charlet-B., Savkur, R., Singh, G, N., Philips, A.V., Grice, E.A., and Cooper, T.A. (2002) Loss of the muscle-specific chloride channel in type 1 myotonic dystrophy due to misregulated alternative splicing. Mol. Cell, 10, 45-53.

26. Gromak, N., Matlin, A.J., Cooper, T.A., and Smith, C.W.J. (2003) Antagonistic regulation of alpha-actinin alternative splicing by CELF proteins and polypyrimidine tract binding protein. RNA 9, 443-456.

27. Singh, G., Charlet-B., N., Han, J., and Cooper, T.A. (2004) ETR-3 and CELF4 protein domains required for RNA binding and splicing activity in vivo. Nucl. Acids Res. 32, 1232-1241.

28. Ladd, A.N., Nguyen, N.H. Malhotra, K and Cooper, T.A. (2004) CELF6, a member of the CELF family of RNA binding proteins, regulates MSE-dependent alternative splicing. J. Biol. Chem. 279,17756-17764.

29. Savkur, R.S., Philips, A.V., Cooper, T.A., Dalton, J.C., Moseley, M.L., Ranum, L.P.W., Day, J.W. (2004) Insulin receptor splicing alteration in myotonic dystrophy type 2. Am. J. Hum. Genet. 74:1309–1313.

30. Ladd, A.N. and Cooper, T.A. (2004) Nuclear-cytoplasmic localization of the RNA binding protein ETR-3 is controlled by multiple localization elements. J. Cell Science 117, 3519-3529.

31. Ho, T., Charlet-B., N., Poulos, M., Singh, G., Swanson, M.S., and Cooper, T.A. (2004) Muscleblind proteins regulate alternative splicing. EMBO J. 23, 3103-3112

32. Faustino, N.A. and Cooper, T.A. (2005) Identification of putative new splicing targets for ETR-3 using its SELEX sequences. Mol. Cell. Biol. 25, 879-887.

33. Ho, T., Bundman, D., Armstrong, D.L., and Cooper, T.A. (2005) Transgenic mice expressing CUG-BP1 reproduce the myotonic dystrophy pattern of splicing. Hum. Mol. Genet. 14, 1539-1547.

34. Han, J. and Cooper, T.A. (2005) Characterization of CELF splicing activation and repression domains in vivo. Nucl. Acids Res. 33, 2769-2780.

35. Ladd, A.L. Stenberg, M.G., Swanson^, M.S., and Cooper, T.A. (2005) A dynamic balance between activation and repression regulates pre-mRNA alternative splicing during heart development. Dev. Dyn. 233, 783-793.

36. Ho, T., Savkur, R.S., Poulos, M., Mancini., M.M., Swanson, M.S., and Cooper, T.A. (2005) Co-localization of muscleblind with RNA foci is separable from mis-regulation of alternative splicing in myotonic dystrophy. J. Cell Science 118 2923-2933.

37. Ladd, A.N., Taffet, G.E., Hartley, C., Kearney, D.L. and Cooper, T.A. (2005) Cardiac-specific repression of CELF activity disrupts alternative splicing and causes cardiomyopathy. Mol. Cell. Biol. 25, 6267-6278.

38. Leroy, O., Wang, J., Maurage, C.A., Parent, M., Cooper, T., Buee, L., Sergeant, N., Andreadis, A., Caillet-Boudin, M.L. (2006) Brain-specific change in alternative splicing of Tau exon 6 in myotonic dystrophy type 1 Biochim Biophys Acta. 1762, 460-467.

39. de Haro, M., Al-Ramahi, I,, De Gouyon, B., Ukani, L., Rosa, A., Faustino, N.A., Ashizawa, T., Cooper, T.A. and Botas, J. (2006) MBNL1 and CUGBP1 modify expanded CUG-induced toxicity in a Drosophila model of Myotonic Dystrophy Type 1. Hum. Mol. Gen. 15, 2138-2145.

40. Singh, G, N. and Cooper, T.A. (2006) A minigene reporter for identification and analysis of cis elements and trans factors affecting pre-mRNA splicing. BioTechniques 41,177-181.

41. Orengo, J., Bundman, D., and Cooper, T.A. (2006) A bichromatic fluorescent reporter for cell-based screens of alternative splicing Nucl. Acids Res. 34, e148.

42. Wang, G.S., Kearney, D.L., De Biasi, M., Taffet, G.E., and Cooper, T.A. (2007) Elevation of RNA-binding protein CUGBP1 is an early event in an inducible heart-specific mouse model of myotonic dystrophy. J. Clin. Invest. 117, 2802-2811.

43. Kuyumcu-Martinez, N.M., Wang, G.S., and Cooper, T.A. (2007) Increased steady state levels of CUG-BP1 in Myotonic Dystrophy 1 are due to PKC-mediated hyper-phosphorylation. Mol. Cell 28, 68-78.

44. Chapple^, J.P., Anthony, K., Martin, T.R., Cooper, J.D. , Cooper, T.A., and Gallo, J-M. (2007) Expression, localization and Tau Exon 10 splicing activity of the brain RNA-binding protein TNRC4. Hum. Mol. Gen. 16, 2760-2769.

45. Dhaenens, C.M., Schraen-Maschke, S., Vingtdeux, V., Vanbrussel, E., Leroy, O., Delplanque, J., Tran, H., Delacourte, A., Vermersch, P., Gruffat, H., Sergeant, A, Mahadevan, M., Ishiura, S., Buée, L:, Cooper, T.A., Caillet-Boudin, M.L., Charlet-Berguerand, N., Sablonnière, B., and Sergeant, N. (2008) Overexpression of MBNL1 fetal isoforms and modified splicing of Tau in the DM1 brain : Two individual consequences of CUG trinucleotide repeats. Experimental Neurology 210, 467-478.

46. Orengo, J.P., Chambon, P., Metzger, D., Mosier, D.R., Snipes, G.J. and Cooper, T.A. (2008) Expanded CTG repeats within the DMPK 3’ UTR causes severe skeletal muscle wasting in an inducible mouse model for myotonic dystrophy. Proc. Nat’l Acad. Sci. 105, 2646-2651.

47. Castle, J.C., Zhang, C., Shah, J.K, Kulkarni, A.V., Kalsotra, A. Cooper, T.A., and Johnson, J.M. (2008) Differential expression of 24,426 human alternative splicing events and predicted cis-regulation in 48 tissues and cell lines. Nat. Genet. 40, 1416-1425.

48. Kalsotra, A., Tran, D., Ward, A., Xiao, X., Burge, C.B., Castle, J.M., Johnson, J.C., and Cooper, T.A. (2008) A conserved program of regulated alternative splicing during vertebrate heart development. Proc. Nat’l Acad. Sci. 105, 20333-20338.

49. Goo, Y.H. and Cooper, T.A. CUGBP2 directly interacts with U2 17S snRNP components and promotes U2 snRNA binding to cardiac troponin T pre-mRNA. Nucl. Acids Res. (In press).

Invited Articles and Reviews

50. Cooper, T.A. and Mattox, W. (1997) The regulation of splice site selection and its role in human disease. Amer. J. Hum. Gen. 61, 259-266.

51. Cooper, T.A. (1999) In vivo SELEX in vertebrate cells in "RNA-Protein Interactions", Susan R. Haynes, Ed.; Methods in Molecular Biology Series, John M. Walker, Ed., (Humana Press), Vol. 118, 405-417.

52. Philips, A.V. and Cooper, T.A. (2000) RNA and human disease. Cell. Mol. Life Sci. 57, 235-249.

53. Cooper, T.A., (2001) Highlights of alternative splicing regulation session: Yes, no, maybe--A history of paradigm shifts. Science STKE, http://www.stke.org/cgi/content/full/OC_sigtrans;2001/105/pe35.

54. Ladd, A.N., Cooper, T.A. (2002) Finding signals that regulate alternative splicing in the post-genomic era. Genome Biology 3, 8.1-8.16.

55. Faustino, A. and Cooper, T.A. (2003) RNA splicing and human disease. Genes Dev. 17, 419-437.

56. Cooper, T.A. (2005) Alternative splicing regulation impacts heart development. Cell 120, 1-2.

57. Cooper, T. A. (2005) In vivo SELEX strategies, p. 840-852. In R. K. Hartmann, A. Bindereif, A. Schon, and E. Westhof (ed.), Handbook of RNA Biochemistry, vol. 2. Wiley-VCH Verlag GmbH and Co, Weinheim.

58. Cooper, T.A. (2005) Use of minigene systems to dissect alternative splicing elements. Methods 37, 331-340.

59. Kuyumcu-Martinez, N.M. and Cooper, T.A. (2006) Mis-regulation of alternative splicing causes pathogenesis in myotonic dystrophy. Prog. in Mol. Subcellular Biol. 44, 133-159.

60. Thornton, C.A., Swanson, M.S., and Cooper, T.A. (2006) The RNA-mediated disease process in myotonic dystrophy. In Genetic Instabilities and Hereditary Neurological Diseases (Second Edition). T. Ashizawa and R.D. Wells (Eds.). p. 37-54.

61. Ranum L.P. and Cooper, T.A. (2006) RNA-mediated neuromuscular disorders. Ann. Rev. Neuroscience 29, 259-277.

62. Cooper, T.A. (2006) A reversal of fortune for myotonic dystrophy? N. Engl. J. Med. 355, 1825-1827.

63. Cooper, T.A. (2007) Regulation of chloride ion conductance during skeletal muscle development and in disease. Amer. J. Physiol: Cell Physiology 292, C1245-1247.

64. Bland, C.S. and Cooper, T.A. (2007) Micromanaging alternative splicing during muscle differentiation. Dev Cell 12, 171-172

65. Orengo, J.P. and Cooper, T.A. (2007) Alternative splicing in disease. in Alternative splicing in the post-genomic era, B.R. Graveley and B. Blencowe, ed. Landes Publishing; pp. 212-223.

66. Wang, G.S. and Cooper T.A. (2007) Splicing in disease: disruption of the splicing code and the decoding machinery. Nature Rev. Genet. 8, 749-761.

67. Cooper, T.A., Wan, L., and Dreyfuss, G. RNA and disease. (2009) Cell 136, 777–793.

68. Lee, J.E. and Cooper, T.A. Pathogenic Mechanisms of Myotonic Dystrophy. Biochem Soc Trans. (In press)

69. Cooper, T.A. Neutralizing toxic RNA. Science (In press)

C. Research Support.

ACTIVE

R01 HL 45565, (Yrs 18-21) (Role: PI) 9/01/08-05/31/12

National of Heart Lung and Blood Institute

"Troponin T Alternative Splicing in Embryonic Heart"

The long term goal of this project is to understand the molecular basis for alternative splicing regulation.

R01 AR/GM 45653, (Yrs 11-15) (Role: PI) 3/1/09-2/28/14

National Institute of Arthritis and Musculoskeletal and Skin Diseases

"Molecular Pathogenesis of Myotonic Dystrophy"

The long term objective of this project is to understand the pathogenic mechanisms of myotonic dystrophy. The objectives are to determine the basis for toxicity of CUG RNA repeats.

R01 GM076493-01 (Role: PI) 2/1/06-1/31/10

National Institute of General Medical Sciences

“Mechanisms of developmentally regulated splicing”

The long term goal of this proposal is to understand the mechanisms by which endogenous alternative splicing regulators modulate natural splicing transitions.

Research Grant 4205 (Role: PI) 1/1/07-12/31/09

Muscular Dystrophy Association

“An inducible mouse model for CNS manifestations of myotonic dystrophy”

The long term objective of this project is to understand the mechanism of pathogenesis of myotonic dystrophy in the CNS.