Assistant Professor, Center for RNA Molecular Biology

Education: Ph.D.: Genetics/Epigenetics, University of Florida College of Medicine, 2005

Postdoc: Harvard Medical School, and The Broad Institute of Harvard and MIT, 2010

Secondary Appointment in: Department of Biochemistry

Email: Click

Office Location: Wood Blgd. W106

Office Phone: 216-368-0710

Office FAX: 216-368-2010

Laboratory Location: RT100

Laboratory Phone: 216-368-4332

Curriculum Vitae

Lab Link

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 large non-coding RNAs may guide chromatin-modifying complexes to genomic loci.  Using state of the art genomic technologies we recently have shown that numerous large non-coding RNAs associate with chromatin-modifying complexes in several mammalian cell types. Through loss-of-function experiments, we found chromatin-associated large non-coding RNAs to be required for proper expression of specific regions of the genome, which are known to be regulated by their associated chromatin-modifying complexes. 

Our current lab efforts are focused on:

1.Further characterization of large non-coding RNAs interactions with   chromatin-modifying complexes and other protein complexes.

2.Elucidating the mechanisms of large non-coding RNAs mediated epigenetic reprogramming.

3.Discovery of meiosis-specific large non-coding RNAs and their role in germ cells development.

4.Determine if mis-regulation of large non-coding RNAs contribute to complex human disorders.

Pubmed Link to Publications

Google Scholar Link to Publications

Select Publications

Geisler, S., Lojek, L., Khalil, A., Baker, K.E., and Coller, J., (2012) A decapping pathway for long non-coding RNAs regulates inducible genes. Mol Cell, 45(3): 279-291.

Huarte M, Guttman M, Feldser D, Garber M, Khalil AM, Zuk O, Amit I, Regev A, Lander ES, Jacks T and Rinn JL. (In Press). A large intergenic noncoding RNA induced by p53 mediates global gene repression in the p53 transcriptional response. Cell

Getun I, Wu ZK, Khalil AM, and Bois PR. (In Press). “The chromatin architecture of mouse recombination hotspots”. EMBO Reports

Khalil AM and Driscoll, D.J. (In Press). “Epigenetic Regulation of Pericentromeric Heterochromatin during Mammalian Meiosis”. Cytogenetics and Genome Research

Khalil AM, Huarte M, and Rinn JL (In Press). The Emerging Non-coding RNA world. Book Title: MicroRNAs in Development and Cancer. Imperial College Press. Editor: Frank Slack, Yale University.

Khalil AM, Guttman M, Huarte M, Garber M, Raj A, Rivera D, Thomas K, Presser A, Bernstein BE, Oudenaarden A, Regev A, Lander ES and Rinn JL. (2009). Many Human Large Non-coding RNAs Associate with Chromatin Modifying Complexes and Affect Gene Expression. PNAS (PMID: 19571010)

Khalil AM. (2009). A geneticist views two theories of X-chromosome inactivation in a broad context. Nature (PMID: 19295563)

Khalil AM, Faghihi MA, Modarresi F, Brother SP and Wahlestedt C. (2008). A Novel RNA Transcript with Antiapoptotic Function Is Silenced in Fragile X Syndrome. PLoS ONE (PMID: 18213394)

Shan G, Li Y, Zhang J, Szulwach K, Qin Y, Duan R, Faghihi M.A., Khalil AM, Lu L, Chan A, Zhou D, Shi Z, Liu Q, Wahlestedt C, He C and Jin P. (2008). A small molecule enhances RNA interference and promotes microRNA processing. Nature Biotechnology (PMID: 18641635)

Faghihi MA, Modarresi F, Khalil AM, Wood DE, Sahagan BG, Morgan TE, Finch CE, St. Laurent III G, Kenny PJ and Wahlestedt C. (2008). Expression of a noncoding RNA is elevated in Alzheimer’s disease and drives rapid feed-forward regulation of b-secretase expression. Nature Medicine (PMID: 18587408)

Khalil AM, and Wahlestedt, C. (2008). Epigenetic Mechanisms of Gene Regulation during Mammalian Spermatogenesis. Epigenetics (PMID: 18416029)

Khalil AM and Driscoll DJ (2007). Trimethylation of Histone H3 Lysine 4 is an Epigenetic Mark at Regions Escaping Mammalian X Inactivation. Epigenetics (Cover Article) (PMID: 17965609)

Khalil AM and Driscoll DJ (2006). Histone H3 Lysine 4 Dimethylation is Enriched on the Inactive X in Male Meiosis but Absent on the Inactive X in Female Somatic Cells. Cytogenetics and Genome Research (PMID:16276085)

Khalil AM. (December 2004). Histone Modifications and Chromatin Dynamics of the Mammalian Inactive Sex Chromosomes. Doctoral Dissertation. University of Florida College of Medicine. 

Khalil AM, Boyar FZ and Driscoll DJ (2004). Dynamic Histone Modifications Mark Sex Chromosome Inactivation and Reactivation during Mammalian Spermatogenesis. PNAS (PMID: 15536132).

PATENTS

2007 A Novel Gene Associated with Fragile X Syndrome and Fragile X Tremor Ataxia Syndrome