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
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.