Area Head, Biological Sciences
Associate Teaching Professor, Biological Sciences
Ihab Younis has been part of the CMU-Q faculty since August 2015. After earning his PhD from Ohio State University in molecular, cellular and developmental biology, he trained as a postdoctoral fellow in the laboratory of Gideon Dreyfuss, Department of Biochemistry and Molecular Biophysics at the University of Pennsylvania, School of Medicine.
In 2013, Younis was promoted to a senior research investigator in the Department of Biochemistry and Molecular Biophysics at the University of Pennsylvania, School of Medicine.
Ph.D., Molecular, Cellular and Developmental Biology, The Ohio State University, USA. Dissertation: Molecular Analysis of Human T-cell Leukemia Virus Regulatory and Accessory Proteins.
M.S., Biology, American University of Beirut, Lebanon. Thesis: Inhibition of 1,2-Dimethylhydrazine-Induced Colon Cancer in Balb-c Mice by Hydrolyzable and Condensed Tannins.
B.S., Biology, American University of Beirut, Lebanon
Area Of Expertise
Molecular biology and biochemistry: Tissue culture, cloning, western blots, northern blots, PCR, real-time PCR, splicing, and recombinant assays. Also developed microarray protocol for quantitative detection of ncRNAs.
High throughput screening of chemical libraries against cell based reporters.
Next generation sequencing: 1) RNA-Seq for measuring nascent transcripts (especially mRNAs) in cells; 2) Crosslinking-IP protocol for detection of splicing aberrations using the exon junction complex; 3) Chromatin-IP coupled with next generation sequencing for detection of RNA polymerase II (and its various phosphorylation variants) across genes.
Younis' lab is studying post-transcriptional regulation of gene expression, specifically intron splicing. The vast majority of human genes contain multiple introns that are removed by the spliceosome in order to connect the protein coding exons in frame. Introns are much larger than exons with vague sequence identifiers, making the task of intron splicing seems almost insurmountable, yet it is done with extreme precision in normal cells. When splicing mistakes occur, they often lead to disease. Splicing misregulation is also a hallmark of cancer cells.
The Younis lab uses a variety of technologies to characterize splicing and its regulation in normal and disease cells, including traditional techniques such as PCR and microarrays, as well as state of the art techniques such as Next Generation Sequencing of nascent pre-mRNA (RNA-seq) and High Throughput Screening (HTS). Using such methodologies, Younis discovered novel drugs that regulate splicing in cancer cells.
The Younis lab has been recently interested in a small set of introns, named minor introns, which are removed by a specialized spliceosome. Identification of all expressed minor introns in human cervical cancer cells led to the discovery that they function as stress-induced molecular switches that control the expression of the genes that harbor them. The mechanism for switching the splicing of minor introns ON or OFF relies on a highly unstable catalytic RNA, U6atac, which is a core component of the minor spliceosome required for the splicing reaction.
Projects in the Younis lab include:
1. A computational biology approach for discovery of splicing aberrations in cancer cells
2. An experimental (molecular biology, cell biology, biochemistry, etc.) approach for validation of splicing aberration in cancer cells and characterization of regulators of the spliceosome.
3. A mix of dry and wet lab projects (a combination of the two approaches above).
gene expression regulation; pre-mRNA splicing; cancer genomics; next generation sequencing; RNA-Seq
So BR, Wan L, Zhang Z, Li P, Babiash E, Duan J, Younis I, and Dreyfuss G. 2015. A U1 snRNP-specific Assembly Pathway Reveals the SMN Complex as a Versatile Hub for RNP Exchange. Nature Structural and Molecular Biology. 23(3): 225-230.
Younis I, Dittmar K, Wang W, Foley SW, Berg MG, Hu KY, Wei Z, Wan L, and Dreyfuss G. 2013. Minor Introns are Embedded Molecular Switches Regulated by Highly Unstable U6atac snRNA. eLife. 2: e00780.
Berg MG, Singh LN, Younis I, Liu Q, Pinto AM, Kaida D, Zhang Z, Cho S, Sherrill-Mix S, Wan L, and Dreyfuss G. 2012. U1 snRNP Determines mRNA Length and Regulates Isoform Expression. Cell. 150: 53-64.
Berg MG, Wan L, Younis I, Diem MD, Soo M, Wang C, and Dreyfuss G. 2012. A Quantitative High-throughput in vitro Splicing Assay Identifies Inhibitors of Spliceosome Catalysis. Molecular and Cellular Biology. 32: 1271-1283.
Kaida D, Berg M, Younis I, Kasim M, Sing LN, Wan L, and Dreyfuss G. 2010. U1 snRNP Protects pre-mRNA from Premature Cleavage and Polyadenylation. Nature. 468: 664-8.
Younis I, Berg M, Kaida D, Dittmar K, Wang C, and Dreyfuss G. 2010. Rapid-Response Splicing Reporter Screens Identify Differential Regulators of Constitutive and Alternative Splicing. Molecular and Cellular Biology. 30: 1718-1728.
Xie L, Kesic M, Yamamoto B, Li M, Younis I, Lairmore MD, and Green PL. 2009. HTLV-2 Rex Carboxy Terminus is an Inhibitory/Stability Domain that Regulates Rex Functional Activity and Viral Replication. J Virology. 83: 5232-43.
Zhang Z, Lotti F, Dittmar K, Younis I, Wan L, Kasim M, and Dreyfuss G. 2008. SMN Deficiency Causes Tissue-Specific Perturbations in the Repertoire of snRNAs and Widespread Defects in Splicing. Cell. 133: 585–600.
Yamamoto B, Li M, Kesic M, Younis I, Lairmore MD, and Green PL. 2008. Human T-cell Leukemia Virus Type 2 Post-Transcriptional Control Protein p28 is Required for Viral Infectivity and Persistence in vivo. Retrovirology. 5: 38.
Diem MD, Chan CC, Younis I, and Dreyfuss G. 2007. PYM Binds the Cytoplasmic Exon Junction Complex and Ribosomes to Enhance Translation of Spliced mRNAs. Nature Structural and Molecular Biology. 14: 1173-9.
Younis I, Boris-Lawrie K, and Green PL. 2006. Human T-cell Leukemia Virus Open Reading Frame II Encodes a Posttranscriptional Repressor that is Recruited at the Level of Transcription. J Virology. 80: 181-91.
Arnold J, Yamamoto B, Li M, Phipps AJ, Younis I, Lairmore MD, and Green PL. 2006. Enhancement of Infectivity and Persistence in vivo by HBZ, a Natural Antisense Coded Protein of HTLV-1. Blood. 107: 3976-82.
Younis I, Yamamoto B, Phipps A, and Green PL. 2005. Human T-cell Leukemia Virus Type 1 Expressing Nonoverlapping Tax and Rex Genes Replicates and Immortalizes Primary Human T Lymphocytes but Fails to Replicate and Persist in vivo. J Virology. 79: 14473-81.
Younis I and Green PL. 2005. The Human T-cell Leukemia Virus Rex Protein. Frontiers in Bioscience. 10: 431-45.
Younis I, Khair L, Dundr M, Lairmore MD, Franchini G, and Green PL. 2004. Repression of Human T-cell Leukemia Virus Type 1 and Type 2 Replication by a Viral mRNA-Encoded Posttranscriptional Regulator. J Virology. 78: 11077-83.
Narayan M, Younis I, D’Agostino DM, and Green PL. 2003. Functional Domain Structure of Human T-cell Leukemia Virus Type 2 Rex. J Virology. 77: 12829-40.
Gali-Muhtasib HU, Younes IH, Karchesy JJ, and el-Sabban ME. 2001. Plant Tannins Inhibit the Induction of Aberrant Crypt Foci and Colonic Tumors by 1,2-Dimethylhydrazine in Mice. Nutrition and Cancer. 39: 108-16.
Gali-Muhtasib HU, Haddadin MJ, Rahhal DN, and Younes IH. 2001. Quinoxaline 1,4-Dioxides as Anticancer and Hypoxia-Selective Drugs. Oncology Reports. 8: 679-84.
CMU-Q representative to the Faculty Senate
2010-present. Member of The RNA Society.
Molecular Biology 03-442
Cancer Biology 03-435