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Ahmad Khalil
Assistant Professor
Ph.D. Training Faculty
Department of Genetics
School of Medicine
Case Western Reserve University
Biomedical Research Building 719
2109 Adelbert Road
Cleveland, Ohio 44106-4955
Tel: (216) 368-0710
Fax: (216) 368-2010
E-mail: ahmad.khalil@case.edu
http://cancerepigenetics.net/


About Ahmad Khalil

Ahmad Khalil earned his PhD at the University of Florida School of Medicine where he elucidated key epigenetic mechanisms that regulate gene expression during mammalian meiosis. Subsequently, he joined the Scripps Research Institute as a postdoctoral fellow (2006-2008) and studied the role of long non-coding RNAs in neurological disorders. In 2008, Dr Khalil moved to Harvard Medical School and the Broad Institute where he played a key role in discovering long intergenic non-coding (linc)RNAs in human cells and show that they play critical roles in epigenetic regulation of gene expression. In 2010, Dr Khalil joined the faculty at CWRU and his lab continues to study the role of lincRNAs in human health and disease.


Research

Epigenetic Regulation by Large Intervening Non-coding (linc)RNA

One of the most fundamental and unsolved problems in biology is: how does the same genome present in every cell of an organism encode a multitude of different cellular states? While epigenetic regulation by chromatin-modifying complexes plays a key role in this process, it is not currently known how these complexes are targeted to specific regions of the genome. We hypothesized that lincRNAs may guide chromatin-modifying complexes to specific genomic loci. Using state of the art genomic technologies we demonstrated that numerous lincRNAs associate with chromatin-modifying complexes in several human cell types (Khalil et al., 2009). Through loss-of-function experiments, we found that this subset of lincRNAs is required for proper expression of specific regions of the genome, which are known to be regulated by their associated chromatin-modifying complexes (Khalil et al., 2009).

These studies suggested that lincRNAs play a critical role in regulating gene expression, and may play critical roles in human biology. Indeed, lincRNAs have been, thus far, implicated in dosage compensation, genomic imprinting, alternative splicing of pre-mRNAs, nuclear organization and nuclear-cytoplasmic trafficking (Moran et al., 2012). Also, the dysregulation of lincRNAs have been observed in many human diseases and disorders including cancer and neurological disorders, suggesting that lincRNAs could be utilized as biomarkers or drug targets (Niland et al., 2012). My lab is currently focusing on elucidating the mechanisms by which lincRNAs exert their effects


Selected Publications

Raffay TM, Dylag AM, Di Fiore JM, Smith LA, Einisman HJ, Li Y, Lakner MM, Khalil AM, MacFarlane PM, Martin RJ, Gaston B (2016)
S-Nitrosoglutathione Attenuates Airway Hyperresponsiveness in Murine Bronchopulmonary Dysplasia.
Mol Pharmacol;90(4):418-26
See PubMed abstract

Zhao Y, Scott A, Zhang P, Hao Y, Feng X, Somasundaram S, Khalil AM, Willis J, Wang Z (2016)
Regulation of paxillin-p130-PI3K-AKT signaling axis by Src and PTPRT impacts colon tumorigenesis.
Oncotarget;:
See PubMed abstract

Merry CR, McMahon S, Forrest ME, Bartels CF, Saiakhova A, Bartel CA, Scacheri PC, Thompson CL, Jackson MW, Harris LN, Khalil AM (2016)
Transcriptome-wide identification of mRNAs and lincRNAs associated with trastuzumab-resistance in HER2-positive breast cancer.
Oncotarget;:
See PubMed abstract

Merry CR, Forrest ME, Sabers JN, Beard L, Gao XH, Hatzoglou M, Jackson MW, Wang Z, Markowitz S, Khalil AM (2015)
DNMT1-associated long non-coding RNAs regulate global gene expression and DNA methylation in colon cancer.
Hum Mol Genet;:
See PubMed abstract

Merry CR, McMahon S, Thompson CL, Miskimen KL, Harris LN, Khalil AM (2015)
Integrative transcriptome-wide analyses reveal critical HER2-regulated mRNAs and lincRNAs in HER2+ breast cancer.
Breast Cancer Res Treat;:
See PubMed abstract

Morton ML, Bai X, Merry CR, Linden PA, Khalil AM, Leidner RS, Thompson CL (2014)
Identification of mRNAs and lincRNAs associated with lung cancer progression using next-generation RNA sequencing from laser micro-dissected archival FFPE tissue specimens.
Lung Cancer;:
See PubMed abstract

Mazar J, Zhao W, Khalil AM, Lee B, Shelley J, Govindarajan S, Yamamoto F, Ratnam M, Aftab MN, Collins S, Finck BN, Han X, Mattick JS, Dinger ME, Perera RJ (2014)
The functional characterization of the long noncoding RNA SPRY4-IT1 in human melanoma cells.
Oncotarget;

Mustafi D, Kevany BM, Bai X, Maeda T, Sears JE, Khalil AM, Palczewski K (2013)
Evolutionarily conserved long intergenic non-coding RNAs in the eye.
Hum Mol Genet;:
See PubMed abstract

Factor D, Tesar PJ, Khalil AM (2013)
Chromatin regulation by long non-coding RNAs
Book title: Molecular Biology of Long Non-coding RNAs.;Springer, 2013 Edition

Moran VA, Perera RJ, Khalil AM (2012)
Emerging functional and mechanistic paradigms of mammalian long non-coding RNAs.
Nucleic Acids Res;40(14):6391-400
See PubMed abstract

Geisler S, Lojek L, Khalil AM, Baker KE, Coller J (2012)
Decapping of long noncoding RNAs regulates inducible genes.
Mol Cell;45(3):279-91
See PubMed abstract

Niland CN, Merry CR, Khalil AM (2012)
Emerging Roles for Long Non-Coding RNAs in Cancer and Neurological Disorders.
Front Genet;3:25
See PubMed abstract

Moran VA, Niland CN, Khalil AM (2012)
Co-Immunoprecipitation of Long Noncoding RNAs.
Methods Mol Biol;925:219-28
See PubMed abstract

Huarte M, Guttman M, Feldser D, Garber M, Koziol MJ, Kenzelmann-Broz D, Khalil AM, Zuk O, Amit I, Rabani M, Attardi LD, Regev A, Lander ES, Jacks T, Rinn JL (2010)
A large intergenic noncoding RNA induced by p53 mediates global gene repression in the p53 response.
Cell;142(3):409-19
See PubMed abstract

Getun IV, Wu ZK, Khalil AM, Bois PR (2010)
Nucleosome occupancy landscape and dynamics at mouse recombination hotspots.
EMBO Rep;11(7):555-60
See PubMed abstract

Khalil AM, Driscoll DJ (2010)
Epigenetic regulation of pericentromeric heterochromatin during mammalian meiosis.
Cytogenet Genome Res;129(4):280-9
See PubMed abstract

Khalil AM, Guttman M, Huarte M, Garber M, Raj A, Rivea Morales D, Thomas K, Presser A, Bernstein BE, van Oudenaarden A, Regev A, Lander ES, Rinn JL (2009)
Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression.
Proc Natl Acad Sci U S A;106(28):11667-72
See PubMed abstract

Khalil AM (2009)
Journal club. A geneticist views two theories of X-chromosome inactivation in a broad context.
Nature;458(7236):263
See PubMed abstract

Shan G, Li Y, Zhang J, Li W, Szulwach KE, Duan R, Faghihi MA, Khalil AM, Lu L, Paroo Z, Chan AW, Shi Z, Liu Q, Wahlestedt C, He C, Jin P (2008)
A small molecule enhances RNA interference and promotes microRNA processing.
Nat Biotechnol;26(8):933-40
See PubMed abstract

Faghihi MA, Modarresi F, Khalil AM, Wood DE, Sahagan BG, Morgan TE, Finch CE, St Laurent G, Kenny PJ, Wahlestedt C (2008)
Expression of a noncoding RNA is elevated in Alzheimer's disease and drives rapid feed-forward regulation of beta-secretase.
Nat Med;14(7):723-30
See PubMed abstract

Khalil AM, Faghihi MA, Modarresi F, Brothers SP, Wahlestedt C (2008)
A novel RNA transcript with antiapoptotic function is silenced in fragile X syndrome.
PLoS One;3(1):e1486
See PubMed abstract

Khalil AM, Driscoll DJ (2007)
Trimethylation of histone H3 lysine 4 is an epigenetic mark at regions escaping mammalian X inactivation.
Epigenetics;2(2):114-8
See PubMed abstract

Khalil AM, Wahlestedt C (2007)
Epigenetic mechanisms of gene regulation during mammalian spermatogenesis.
Epigenetics;3(1):21-8
See PubMed abstract

Khalil AM, Driscoll DJ (2006)
Histone H3 lysine 4 dimethylation is enriched on the inactive sex chromosomes in male meiosis but absent on the inactive X in female somatic cells.
Cytogenet Genome Res;112(1-2):11-5
See PubMed abstract

Khalil AM, Boyar FZ, Driscoll DJ (2004)
Dynamic histone modifications mark sex chromosome inactivation and reactivation during mammalian spermatogenesis.
Proc Natl Acad Sci U S A;101(47):16583-7
See PubMed abstract