Klemens J. Hertel, Ph.D.

Department of Microbiology and Molecular Genetics

School of Medicine

University of California, Irvine

Med Sci B233

Irvine, CA 92697-4025

(949) 824-2127

khertel@uci.edu

http://jeeves.mmg.uci.edu/hertel/

 

Education

1983-1986            Colorado College, Colorado Springs, CO, USA; Bachelor of Art, Biology (6/86)

1987-1988            Albert-Ludwig-Universität, Freiburg, Germany; Chemistry, Vordiplom Physikalische Chemie (7/88)

1988-1993            University of Colorado, Boulder, CO, USA; Doctor of Philosophy, (12/93), Biochemistry

 

Research and Professional Experience

1985-1986            Undergraduate research with Professor Nathan Bower,Department of Chemistry, Colorado College, Colorado Springs

1986-1987            Paraprofessional, Department of Chemistry, Colorado College, Colorado Springs

1988-1993            Graduate student with Professor Olke C. Uhlenbeck, Department of Chemistry and Biochemistry, University of Colorado, Boulder

1994-1999            Postdoctoral Fellow with Professor Tom Maniatis, Department of Molecular & Cellular Biology, Harvard University, Cambridge

1999-2007            Assistant Professor, Department of Microbiology and Molecular Genetics, School of Medicine, University of California, Irvine

2008-2009            Gastprofessor, Institut für Informatik, Lehrstuhl für Bioinformatik, Albert-Ludwigs-Universität Freiburg, Germany

2007-present            Associate Professor, Department of Microbiology and Molecular Genetics, School of Medicine, University of California, Irvine

 

Teaching Experience

1986-1987            Paraprofessional - laboratory in chemistry and biochemistry; Department of Chemistry, Colorado College, Colorado Springs

1988-1989            Teaching assistant - laboratory in organic chemistry, Department of Chemistry and Biochemistry, University of Colorado, Boulder

2001-present            Regulation of Gene Expression, Structure and Biosynthesis of Nucleic Acids, and Special Topics courses for graduate students, University of California, Irvine

2002-2006            Medical Microbiology laboratory course, University of California, Irvine

 

Professional Societies

            RNA Society

            American Society for Biochemistry and Molecular Biology

 

Honors and Scholarships

1983-1986            Foreign Student Scholarship, Colorado College, Colorado Springs

1985, 1986            Deans List, Colorado College, Colorado Springs

1989            John S. Meck Award for "Excellence in Teaching", University of Colorado, Boulder

1994-1997            Jane Coffin Childs Memorial Fund for Medical Research Postdoctoral Fellowship

2002            W. M. Keck Foundation, Distinguished Young Scholars in Medical Research, Semi-finalist

2005            Faculty Career Development Award, University of California, Irvine

2006            Department of Defense Concept Award

 

Publications

Journal Articles (peer-reviewed)

1) Bower, N., Hertel, K., Oh, J., and Storey, R. 1988. Nutritional evaluation of morama bean (Tylosema esculentum, Fabaceae): Analysis of the seed. Economic Botany 42: 533-540.

 

2) Hertel, K.J., Pardi, A., Uhlenbeck, O.C., Koizumi, M., Ohtsuka, E., Uesugi, S., Cedergren, R., Eckstein, F., Gerlach, W.L., Hodgson, R., and et al. 1992. Numbering system for the hammerhead. Nucleic Acids Res 20: 3252.

 

3) Hertel, K.J., Herschlag, D., and Uhlenbeck, O.C. 1994. A kinetic and thermodynamic framework for the hammerhead ribozyme reaction. Biochemistry 33: 3374-3385.

 

4) Hertel, K.J. and Uhlenbeck, O.C. 1995. The internal equilibrium of the hammerhead ribozyme reaction. Biochemistry 34: 1744-1749.

 

5) Stage, T.K., Hertel, K.J., and Uhlenbeck, O.C. 1995. Inhibition of the hammerhead ribozyme by neomycin. RNA 1: 95-101.

 

6) Hertel, K.J., Herschlag, D., and Uhlenbeck, O.C. 1996. Specificity of hammerhead ribozyme cleavage. EMBO J 15: 3751-3757.

 

7) Hertel, K.J., Lynch, K.W., Hsiao, E.C., Liu, E.H., and Maniatis, T. 1996. Structural and functional conservation of the Drosophila doublesex splicing enhancer repeat elements. RNA 2: 969-981.

 

8) Hertel, K.J., Peracchi, A., Uhlenbeck, O.C., and Herschlag, D. 1997. Use of intrinsic binding energy for catalysis by an RNA enzyme. Proc Natl Acad Sci U S A 94: 8497-8502.

 

9) Graveley, B.R., Hertel, K.J., and Maniatis, T. 1998. A systematic analysis of the factors that determine the strength of pre-mRNA splicing enhancers. EMBO J 17: 6747-6756.

 

10) Hertel, K.J. and Maniatis, T. 1998. The function of multisite splicing enhancers. Mol Cell 1: 449-455.

 

11) Hertel, K.J., Stage-Zimmermann, T.K., Ammons, G., and Uhlenbeck, O.C. 1998. Thermodynamic dissection of the substrate-ribozyme interaction in the hammerhead ribozyme. Biochemistry 37: 16983-16988.

 

12) Hertel, K.J. and Maniatis, T. 1999. Serine-arginine (SR)-rich splicing factors have an exon-independent function in pre-mRNA splicing. Proc Natl Acad Sci U S A 96: 2651-2655.

 

13) Graveley, B.R., Hertel, K.J., and Maniatis, T. 2001. The role of U2AF35 and U2AF65 in enhancer-dependent splicing. RNA 7: 806-818.

 

14) Lim, S.R. and Hertel, K.J. 2001. Modulation of survival motor neuron pre-mRNA splicing by inhibition of alternative 3' splice site pairing. J Biol Chem 276: 45476-45483.

 

15) Lam, B.J. and Hertel, K.J. 2002. A general role for splicing enhancers in exon definition. RNA 8: 1233-1241.

 

16) Lam, B.J., Bakshi, A., Ekinci, F.Y., Webb, J., Graveley, B.R., and Hertel, K.J. 2003. Enhancer-dependent 5'-splice site control of fruitless pre-mRNA splicing. J Biol Chem 278: 22740-22747.

 

17) Lim, S.R. and Hertel, K.J. 2004. Commitment to splice site pairing coincides with A complex formation. Mol Cell 15: 477-483.

 

18) Ibrahim el, C., Schaal, T.D., Hertel, K.J., Reed, R., and Maniatis, T. 2005. Serine/arginine-rich protein-dependent suppression of exon skipping by exonic splicing enhancers. Proc Natl Acad Sci U S A 102: 5002-5007. [related commentary appears in Proc Natl Acad Sci U S A 102: 4927-4928].

 

19) Freund, M.*, Hicks, M.J.*, Konermann, C., Otte, M., Hertel, K.J. #, and Schaal, H. # 2005. Extended base pair complementarity between U1 snRNA and the 5' splice site does not inhibit splicing in higher eukaryotes, but rather increases 5' splice site recognition. Nucleic Acids Res 33: 5112-5119. *Joint first authors; #joint corresponding author

 

20) Fox-Walsh, K.L., Dou, Y., Lam, B.J., Hung, S.P., Baldi, P.F., and Hertel, K.J. 2005. The architecture of pre-mRNAs affects mechanisms of splice-site pairing. Proc Natl Acad Sci U S A 102: 16176-16181.

 

21) Madocsai, C., Lim, S.R., Geib, T., Lam, B.J., and Hertel, K.J. 2005. Correction of SMN2 Pre-mRNA splicing by antisense U7 small nuclear RNAs. Mol Ther 12: 1013-1022.

 

22) Hicks, M.J., Yang, C.R., Kotlajich, M.V., and Hertel, K.J. 2006. Linking splicing to Pol II transcription stabilizes pre-mRNAs and influences splicing patterns. PLoS Biol 4: e147, 943-951. [related commentary appears in ACS Chem Biol 1:, 264–269]

 

23) Dou, Y.*, Fox-Walsh, K.L.*, Baldi, P.F., and Hertel, K.J. 2006. Genomic splice-site analysis reveals frequent alternative splicing close to the dominant splice site. RNA, 12: 2047-2056. *Joint first authors.

 

24) Sciabica, K. S., and Hertel, K.J. 2006. The splicing regulators Tra and Tra2 are unusually potent activators of pre-mRNA splicing. Nucleic Acids Res, doi: 10.1093/nar/gkl984.

 

25) Shepard, P.J., and Hertel, K.J. 2008. Conserved RNA secondary structures promote alternative splicing. RNA 14: 1463-1469.

 

26) Kotlajich, M.V., Crabb, T.L., and Hertel, K.J. 2009. Spliceosome assembly pathways for different types of alternative splicing converge during commitment to splice-site pairing in A-complex. Mol Cell Bio 29: 1072-1082.

 

27) Fox-Walsh, K.L., and Hertel, K.J. 2009. Splice-site pairing is an intrinsically high fidelity process. Proc Natl Acad Sci U S A 106: 1766-1771.

 

Geib, T., and Hertel, K.J. 2009. Restoration of full-length SMN promoted by Adenoviral vectors expressing RNA antisense oligonucleotides embedded in U7 snRNAs. In review.

 

Review Articles (peer-reviewed)

1) Uhlenbeck, O.C., Khripine, Y., Long, D.M., Pan, T., Derrick, W.S., and Hertel, K.J. 1993. Using in vitro evolution to find new RNA catalysis. 40 years of the DNA double helix. Houston, Texas: The Robert A. Welch Foundation Conference XXXVII.

 

2) Hertel, K.J., Lynch, K.W., and Maniatis, T. 1997. Common themes in the function of transcription and splicing enhancers. Curr Opin Cell Biol 9: 350-357.

 

3) Graveley, B.R., Hertel, K.J., and Maniatis, T. 1999. SR proteins are 'locators' of the RNA splicing machinery. Curr Biol 9: R6-7.

 

4) Graveley, B.R. and Hertel, K.J. 2005. The SR protein family. Encyclopedia of the Human Genome: Nature Publishing Group. pp doi: 10.1038/npg.els.0005039ls.

 

5) Hertel, K.J. and Graveley, B.R. 2005. RS domains contact the pre-mRNA throughout spliceosome assembly. Trends Biochem Sci 30: 115-118.

 

6) Hicks, M.J., Lam, B.J., and Hertel, K.J. 2005. Analyzing mechanisms of alternative pre-mRNA splicing using in vitro splicing assays. Methods 37: 306-313.

 

7) Hertel, K.J. 2008. Combinatorial control of exon recognition. J Biol Chem 283: 1211-1215.

 

8) Kotlajich, M.V., and Hertel, K.J. 2008. Death by splicing: tumor suppressor RBM5 freezes splice-site pairing. Mol Cell 32: 162-164.

 

9) Klaue, Y., and Hertel, K.J. 2009. Dangerous play - splitting the message may leave you empty-handed. Nat Str Mol Bio, in press.

 

10) Hsu, S.N., and Hertel, K.J. 2009. Spliceosomes walk the line: splicing errors and their impact on cellular function. RNA Bio, in press.

 

Podcasts

·Alternative Gene Splicing, J Biol Chem News, Jan 18, 2008

 

Patents

·Long, D.M., Hertel, K.J., and Uhlenbeck O.C.  “Ligation with hammerhead ribozymes.” Filed 07/94, accepted 04/97.  U.S. serial No. 08/275,156.

 

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