Graduate and Post-Doctoral Opportunities
Dr. Cooper is a member of five graduate programs:
- Molecular Physiology and Biophysics Graduate Program
- Interdepartmental Program of Cell and Molecular Biology
- Department of Molecular and Cellular Biology
- Translational Biology & Molecular Medicine
- Program in Developmental Biology
Alternative splicing regulation identification:
- Components of splicing activation and repression complexes
- Basis for coordinated regulation during development
- Signaling events modulating splicing regulators
Myotonic Dystrophy pathogenesis
- Develop and use existing mouse models to investigate myotonic dystrophy pathogenesis
- Identify molecular basis for skeletal muscle, cardiac, and CNS symptoms in DM
- Determine pathogenic form of the toxic RNA
Contact Dr. Cooper for more information about specific projects.
Our lab strives to provide a scholarly, highly interactive, and productive scientific environment. The best ideas arise through consultation and discussion within and outside of the lab. Scientific investigations are most rewarding when they are goal-oriented, explore new areas, are directed toward understanding mechanisms, and have the potential for an important impact on human health. We believe that science is an exciting and rewarding career worthy of the invested time and energy.
Baylor College of Medicine provides a unique environment of outstanding research, collegiality and collaboration. From its excellent diversity of core facilities (including microarray, transgenic/KO mice, protein sequencing-mass spec), 14 graduate programs, multiple weekly seminar series to choose from, to its active postdoc association, Baylor is an active and well supported research community. Note that we are not associated with Baylor University (so we don't have a football team).
Our lab interacts regularly with at least ten other local labs focused on different aspects of RNA processing located at The MD Anderson Cancer Center , Rice University , and The University of Texas Health Science Center at Houston . These labs gather monthly for RNA Group Meeting , an informal joint lab meeting in which one lab presents recent results. This is a great opportunity to get outside input prior to submission or for project development. These labs also participate in a regular journal club. All of these institutions are located within the Texas Medical Center , the largest medical center in the world, a complex of more than 46 institutions including 13 academic institutions and populated by more than 90,000 people.
Goals for trainees are to attain the abilities to independently: identify significant and practical scientific questions, design systematic strategies to address these questions, present ideas and findings orally in a variety of settings, from talking one-on-one to informal lab meetings and formal seminars, write up and submit results for publication, and prepare a grant proposal. Trainees are encouraged and supported to attend and present at national meetings. These should be the goals of people who are considering joining the lab. Rather than passively allowing trainees to sink or swim, Dr. Cooper believes that training for a scientific career is an active process involving ongoing interactions with and feedback from the PI.
Houston is the fourth largest city in the U.S. with a population of 4 million. Activities abound (see Houston links on Links of interest page) including opera, ballet, symphony, live theater, a large museum district (Houston is third in the country in the number of working visual artists), major-league sports (baseball, football, basketball), Galveston beaches (40 mile drive) and a huge number of restaurants offering a large variety of ethnic cuisine. A light rail system connects the medical center to downtown. Houston has all the amenities of a large city while being an affordable, friendly, and "easy" city in which to live. The bottom line is that, almost without exception, everyone who visits is impressed and surprised by what they didn't know (but thought they knew). Temperatures are cool and dry from fall to spring rarely dropping below freezing in the winter. Summer temperatures are in the 90's with moderate-high humidity but hey, it's air-conditioned everywhere.
Publications from Graduate Students and Post-docs
Lee, J.E., Bennett, C.F. and Cooper, T.A. (2012) RNase H-mediated degradation of toxic RNA in myotonic dystrophy type 1. Proc. Nat'l Acad. Sci. 109, 4221-4226.
Echeverria, G. V. and Cooper, T. A. (2012) RNA-binding proteins in microsatellite expansion disorders: mediators of RNA toxicity. Brain Research 1462, 100-111.
Singh, R. and Cooper, T. A. (2012) Pre-mRNA splicing in disease and therapeutics. Trends in Molecular Medicine 18, 472-482.
Kalsotra, A. and Cooper, T. A. (2011) Functional consequences of developmentally regulated alternative splicing Nature Rev. Genet. 12, 715-729.
Grammatikakis, I. Goo, Y.H., Echeverria, G.V., and Cooper, T.A. (2011) Identification of MBNL1 and MBNL3 domains required for alternative splicing activation and repression. Nucl. Acids Res. 39, 2769-2780.
Orengo, J.P., Ward, A.J., and Cooper T.A. (2011) Alternative splicing misregulation secondary to skeletal muscle regeneration. Annals Neurology 69, 681-690.
Meerbrey, K.L., Hu, G., Kessler, J.D., Roarty, K., Li, M.Z., Fang, J.E., Herschkowitz, J.I., Burrows, A.E., Ciccia, A., Sun, T., Schmitt, E.M., Bernardi, R.J., Fu, X., Bland, C.S., Cooper, T.A., Schiff, R., Rosen, J.M., Westbrook, T.F., Elledge, S.J. (2011) The pINDUCER lentiviral toolkit for inducible RNA interference in vitro and in vivo. Proc Natl Acad Sci U S A. 108, 3665-3670.
Bland, C.S., Wang, E.T., Vu, A., David, M.P., Castle, J.C., Johnson, J.M., Burge, C.B., and Cooper, T.A. (2010) Global regulation of alternative splicing during myogenic differentiation. Nucl. Acids Res. 38, 7651-7654
Ward, A.J., Rimer, M., Killian, J.M., Dowling, J.J., Cooper, T.A. (2010) CUGBP1 overexpression in mouse skeletal muscle reproduces features of myotonic dystrophy type 1. Hum Mol Genet. 19, 3614-3622
Lee, J.E. and Cooper, T.A. (2009) Pathogenic Mechanisms of Myotonic Dystrophy. Biochem Soc Trans. 37, 1281-1286.
Kalsotra, A., Wang, K, Li, P.-F., and Cooper, T. A. (2010) MicroRNAs coordinate an alternative splicing network during mouse postnatal heart development. Genes Dev. 24, 653-658.
Koshelev, M.V., Sarma, S., Wehrens, X.H.T., and Cooper, T.A. (2010) Heart-specific expression of CUGBP1 in transgenic mice reproduces electrocardiographic and functional abnormalities of DM1. Hum. Mol. Genet. 19, 1066-1075.
Ward, A. and Cooper, T.A. (2010) The pathobiology of alternative splicing. J. Path. 220, 152-163.
Wang, G.S., Kuyumcu-Martinez, N.M., Mathur, N., Wehrens, X.H., and Cooper, T.A. (2009) Protein kinase C inhibition ameliorates the cardiac phenotype of a mouse model for myotonic dystrophy, type 1. J. Clin. Invest. 119, 3797-3806. Lee, J.E. and Cooper, T.A. (2009) Pathogenic Mechanisms of Myotonic Dystrophy. Biochem Soc Trans. Biochem Soc Trans. 37, 1281-1286.
Goo, Y.H. and Cooper, T.A. (2009) CUGBP2 directly interacts with U2 17S snRNP components and promotes U2 snRNA binding to cardiac troponin T pre-mRNA. Nucl. Acids Res. 37, 4275-4286.
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.
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.
Orengo, J.P., Chambon, P., Metzger, D., Mosier, D.R., Snipes, G.J. and Cooper, T.A. (2008) Expanded CTG repeats within the DMPK 3¹ UTR causes severe skeletal muscle wasting in an inducible mouse model for myotonic dystrophy. Proc. Nat¹l Acad. Sci. 105, 2646-2651.
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.
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.
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.
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.
Bland, C.S. and Cooper, T.A. (2007) Micromanaging alternative splicing during muscle differentiation Dev Cell 12, 171-172
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.
de Haro, M., Al-Ramahi, I,, De Gouyon, B., Ukani, L., Rosa, A., Faustino, N.A., Ashizawa, T., Cooper, T.A. and Botas, J. MBNL1 and CUGBP1 modify expanded CUG-induced toxicity in a Drosophila model of Myotonic Dystrophy Type 1. Hum. Mol. Gen. (In Press).
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.
Han, J. and Cooper, T.A. (2005) Characterization of CELF splicing activation and repression domains in vivo Nucl. Acids Res. 33, 2769-2780.
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.
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.
Ladd, A.N. 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.
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.
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.
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
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.
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.
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.
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.
Faustino, N.A. and Cooper, T.A. (2003) RNA splicing and human disease. Genes Dev. 17, 419-437.
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.
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.
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.
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.
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.
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.
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.
Philips, A.V. and Cooper, T.A. (2000) RNA and human disease. Cell. Mol. Life Sci. 57, 235-249.
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.
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.
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.