Stefan Maas, Ph.D.
Assistant Professor
Molecular Biology

Phone: 610-758-6276
Email: swm3@lehigh.edu

Research Summary

Our lab is interested in understanding the molecular basis for the tremendous complexity and diversity of higher organisms. This complexity is based on the number of different gene products available for structural, enzymatic and regulatory functions. Recently, whole-genome sequencing of a diverse set of species from primitive to highly developed organisms (bacteria, yeast, worm, fly, fish, mouse, human) has demonstrated that during evolution the number of building blocks (genes) in genomes, has not increased at the same rate as the observed organismic complexity (for example: fruit fly 13,000 genes, homo sapiens ca. 30,000 genes). This unexpected finding underscores the important role of post-transcriptional and post-translational mechanisms for the generation of protein diversity.

We are focusing on a recently discovered phenomenon of pre-mRNA modification, called RNA editing. In general, the term RNA editing is used to describe the posttranscriptional alteration of gene sequences by different mechanisms including the deletion, insertion and modification of nucleotides. Base changes in codons often lead to amino acid changes and result in alteration of protein function.
In mammals, the modification of adenosines (A) to inosine (I) appears to be particularly widespread and is known to regulate crucial functional properties of neurotransmitter receptors in the brain. Since inosine acts as guanosine during translation it can change the readout of edited codons. The coexpression of edited and unedited protein variants in the same cell can increase exponentially the number of gene products generated from a single gene. A-to-I RNA editing is catalyzed by the ADAR (adenosine deaminase acting on RNA) family of enzymes and these proteins recognize a double-stranded RNA structure formed from exonic and intronic sequences within the substrate molecule.

In addition to the recoding of mRNA information, the modification of RNAs by ADARs could potentially affect any biological process that involves sequence- or structure-specific interactions with RNA.

We use molecular biological, biochemical and genetics approaches to study how prevalent A-to-I RNA editing is in the transcriptome and how it is regulated. Furthermore, we investigate the consequences of misregulation of or deficiency in RNA editing and how it can contribute to pathophysiological processes.

Publications

Maas, S. and Gommans, W.M., 2009: Identification of a selective nuclear import signal in adenosine deaminases acting on RNA. Nucleic Acids Res., in press

Gommans, W.M., Mullen S.P. and Maas, S. 2009: RNA editing: a driving force for adaptive evolution? BioEssays, 31(10), in press

Sie, C.P., and Maas, S. 2009: Conserved recoding RNA editing of vertebrate C1q-related factor C1QL1. FEBS letters, 583:1171-1174, Epub 2009 Mar 9

Atwood, C., Boyden, E., Celikel, T., Culurciello, E., Dzakpasu, R., Heilshorn, S., Kello, C., Lathrop, D., Litt, B., Maas, S., Sporns, O., Sternad, D., and Lee, J.L. 2009: Bridging complexity and Neuroscience in health and disease. In: Complex Systems: Task group summaries of the National Academies Keck Futures Initiative Complex Systems Conference. National Academies Press; pp 49-58

Maas, S. and Gommans, W.M., 2009: Novel exon of mammalian ADAR2 extends open reading frame. PLoS ONE,4(1):e4225. Epub 2009 Jan 19

Gommans, W.M., and Maas, S. 2008: Characterization of ADAR1-mediated modulation of gene expression. Biochemical and Biophysical Research Communications, 377(1):170-5, Epub 2008 Oct 7

Gommans, W.M., Tatalias, N.E., Sie, C., Dupuis, D.E., Vendetti, N.J., Smith, L., Kaushal, R., and Maas, S. 2008: Screening of human SNP database identifies recoding sites of A-to-I RNA editing. RNA, 14 (10), 2074-85, Epub 2008 Sep 4.

Orlowski, R.J., O'Rourke, K.S., Olorenshaw, I., Hawkins, G.A., Maas, S., and Laxminarayana, D., 2008: Altered Editing in Cyclic Nucleotide Phosphodiesterase 8A1 (PDE8A1) Gene Transcripts of Systemic Lupus Erythematosus (SLE) T Lymphocytes. Immunology, 125(3):408-19, Epub 2008 May 6.

Wynne, R.D., Maas, S., and Saldanha, C.J., 2008: Molecular characterization of the injury-induced aromatase transcript in the adult zebra finch brain. J Neurochem., 105(5):1613-24, Epub 2008 Feb 26.

Gommans, W.M., Dupuis, D.E., McCane, J.E., Tatalias, N.E., and Maas, S., 2008: Diversifying Exon Code through A-to-I RNA Editing. In: DNA and RNA Editing: Mechanisms and Functions; Wiley publishers; edited by: Harold Smith, pp3-30

Laxminarayana, D., O'Rourke, K.S., Maas, S., and Olorenshaw, I., 2007: Altered Editing in RNA editing Adenosine Deaminase ADAR2 Gene Transcripts of Systemic Lupus Erythematosus (SLE) T Lymphocytes. Immunology, 121(3):359-69, Epub 2007 Mar 22.

Lopresti, D., Drake, D. Kaushal, R. Hookway, S. Scheirer, W. Strohmaier, M., Wojciechowski, C., and Maas, S. 2006: A Bioinformatics Approach to Identify Recoding Events of A-to-I RNA Editing, Proceedings of the Computational Systems Bioinformatics Conference, CSB, Palo Alto, CA, 5 pages,

Maas, S., Kawahara, Y., Tamburro, K., and Nishikura, K 2006: A-to-I RNA Editing and Human Disease. RNA Biology, 3(1), e1-9, Epub 2006 Jan 12. PDF
Listen to the abstract!

Koeris, M., Funke, L., Shrestha, J., Rich. A., and Maas , S. 2005: Modulation of ADAR1 editing activity by Z-RNA in vitro. Nucleic Acids Res., 33 (16): 5362-70. Cover issue. PDF

Athanasiadis, A., Placido, D., Maas, S., Brown, B.A.2nd, Lowenhaupt, K., and Rich, A., 2005: The crystal structure of the Zbeta domain of the RNA-editing enzyme ADAR1 reveals distinct conserved surfaces among Z-domains . J Mol Biol , 351 (3): 496-507. PDF

Athanasiadis, A., Rich, A., and Maas, S. 2004: Widespread A-to-I RNA editing of Alu-containing mRNAs in the human transcriptome. PLoS Biology, 2 (12), e391, 1-15, Epub 2004 Nov 9. PDF

Luciano, D.J., Mirsky, H., Vendetti, N.J., and Maas, S. 2004: RNA editing of a miRNA precursor. RNA, 10, 1174-77. PDF

Maas, S., Rich, A., and Nishikura, K., 2003: A-to-I RNA editing: recent news and residual mysteries. J.Biol.Chem. 278, 1391-1394, Review article. PDF

Tsibris, J.C.M., Maas, S., Segars, J.H., Nicosia, S.V., Enkemann, S.A., O’Brien, W.F., and Spellacy, W.N. 2003: New potential regulators of uterine leiomyomata from DNA arrays: The ionotropic glutamate receptor GluR2. Biochem Biophys Res Commun, 312, 249-254. PDF

Kim, Y.G., Maas, S., and Rich, A. 2001: Comparative mutational analysis of cis-acting RNA signals for translational frameshifting in HIV-1 and HTLV-2. Nucleic Acids Res. 29 (5), 1125-1131

Maas, S., Kim, Y.G., and Rich, A. 2001: Genomic clustering of tRNAAla-specific adenosine deaminase ADAT1 and two tRNA-synthetases within a susceptibility locus for autoimmune diseases. Mamm Genome 12 (5), 387-393

Kim, Y.G., and Maas, S., 2001: Efficient multiple site mutagenesis in vitro. In: Methods in Molecular Biology, vol. 182: In Vitro Mutagenesis, 2nd ed., pp 29-36

Maas, S., Patt, S., Schrey, M., and Rich, A., 2001: Underediting of GluR-B mRNA in malignant gliomas. Proc. Natl. Acad. Sci.USA 98 (25), 14687-14692. PDF (see also: Editor's choice in Science Dec. 14, 2001 and in MIT TechTalk)

Kim, Y.G., and Maas, S., 2000: Efficient multiple site mutagenesis with high targeting efficiency in one cloning step. BioTechniques 28, 196-198

Kim, Y.G., Maas, S., Wang, S., and Rich, A. 2000: Mutational study reveals that tertiary interactions are conserved in ribosomal frameshifting pseudoknots of two luteoviruses. RNA 6, 1157-1165

Maas, S., and Rich, A. 2000: Changing genetic information through RNA editing. BioEssays 22, 790-802, Review article

Kim, Y.-G., Lowenhaupt, K., Maas, S., Herbert, A., Schwartz, T., and Rich, A. 2000: The Z-DNA binding domain of ADAR1 induces formation of Z-DNA in a B-DNA environment. J.Biol.Chem. 275, 26828-26833

Maas, S., Kim, Y.G., and Rich, A. 2000: Sequence, genomic organization and functional expression of the murine tRNA-specific adenosine deaminase ADAT1. Gene 243, 59-66

Higuchi, M., Maas, S., Single, F.N., Hartner, J., Rozov, A., Burnashev, N., Feldmeyer, D., Sprengel, R., and Seeburg. P.H., 2000: Point mutation in an AMPA receptor gene rescues lethality in mice deficient in the RNA-editing enzyme ADAR2. Nature 406, 78-81

Kim, Y.G., Su, L., Maas, S., O’Neill, A., and Rich, A. 1999: Specific mutations in a viral RNA pseudoknot drastically change ribosomal frameshifting efficiency. Proc. Natl. Acad. Sci.USA 96 (25), 14234-14239

Maas, S., 1999: Efficient and rapid procedure for blue-white screening of recombinant bacterial clones. BioTechniques 27, 1126-1128

Maas, S., Gerber, A.P., and Rich, A. 1999: Identification and characterization of a human tRNA-specific adenosine deaminase related to the ADAR family of pre-mRNA editing enzymes. Proc. Natl. Acad. Sci.USA 96, 8895-8900

Maas, S., Melcher, T., and Seeburg, P.H. 1997: Mammalian RNA-dependent deaminases and edited mRNAs. Curr. Opin. Cell Biol. 9, 343-349, Review article

Melcher, T., Maas, S., Herb, A., Sprengel, R., Higuchi, M., and Seeburg, P.H. 1996: Red2, a brain specific member of the RNA-specific adenosine deaminase family. J.Biol.Chem. 271, 31795-31798

Maas, S., Melcher, T., Herb, A., Seeburg, P.H., Keller, W., Krause, S., Higuchi, M., and O'Connell, M. 1996: Structural requirements for RNA editing in glutamate receptor pre-mRNAs by recombinant double-stranded RNA adenosine deaminase. J.Biol.Chem. 271, 12221-12226

Melcher, T.*, Maas, S.*, Herb, A., Sprengel, R., Seeburg, P.H., and Higuchi, M. 1996: A mammalian RNA editing enzyme. Nature 379, 460-464

* equally contributing first authors

Melcher, T., Maas, S., Higuchi, M., Keller, W., and Seeburg, P.H. 1995: Editing of AMPA receptor GluR-B pre-mRNA in vitro reveals site-selective adenosine to inosine conversion J.Biol.Chem. 270, 8566-8570

Patt, S., Thiel, G., Maas, S., Lozanova, T., Prosenc, N., Cervos-Navarro, J., Witkowski, R., and Blumenstock, M., 1993: Chromosomal changes and correspondingly altered protooncogene expression in human gliomas. Anticancer Res. 13, 113-118

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