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Ahmad M Khalil, Ph.D.
Assistant Professor of Genetics and Genome Sciences
Case Western Reserve University School of Medicine
Postdoctoral Training, Completed 2010
Harvard Medical School and The Broad Institute
PhD, Awarded 2005
University of Florida College of Medicine
Email: Ahmad.Khalil@case.edu
Assistant Professor of Genetics and Genome Sciences
Case Western Reserve University School of Medicine
Postdoctoral Training, Completed 2010
Harvard Medical School and The Broad Institute
PhD, Awarded 2005
University of Florida College of Medicine
Email: Ahmad.Khalil@case.edu
Our Research Interests:
Our research team is working on discovering key long intergenic non-coding RNAs (lincRNAs) that become deregulated in human cancers, and elucidating their biological functions. We are using both in vitro (patient-derived cell lines) and in vivo (tumors from patients) to pinpoint critical lincRNAs.
lincRNAs have only been discovered several years ago, and thus, provide a great opportunity to explore novel therapeutic targets in cancer biology. To date, several lincRNAs have been implicated in cancer initiation, progression and metastasis (see our review articles: Niland et al, 2012; Moran et al, 2012), however, a number of key questions remain: 1. Are lincRNAs drivers of cancer?, 2. Are there specific mutations or epigenetic alterations of lincRNA loci that are sufficient to initiate tumorigenesis?, 3. What are the functions and mechanisms of lincRNAs in normal biology and in disease states?
Our current research is attempting to provide answers to these critical questions with the hope that lincRNAs can be used in future RNA-based therapeutic approaches to treat cancer as well as other human conditions.
Our research team is working on discovering key long intergenic non-coding RNAs (lincRNAs) that become deregulated in human cancers, and elucidating their biological functions. We are using both in vitro (patient-derived cell lines) and in vivo (tumors from patients) to pinpoint critical lincRNAs.
lincRNAs have only been discovered several years ago, and thus, provide a great opportunity to explore novel therapeutic targets in cancer biology. To date, several lincRNAs have been implicated in cancer initiation, progression and metastasis (see our review articles: Niland et al, 2012; Moran et al, 2012), however, a number of key questions remain: 1. Are lincRNAs drivers of cancer?, 2. Are there specific mutations or epigenetic alterations of lincRNA loci that are sufficient to initiate tumorigenesis?, 3. What are the functions and mechanisms of lincRNAs in normal biology and in disease states?
Our current research is attempting to provide answers to these critical questions with the hope that lincRNAs can be used in future RNA-based therapeutic approaches to treat cancer as well as other human conditions.
We use genome-wide approaches to determine which coding and non-coding genes are deregulated in cancer:
We are focusing on long intergenic non-coding (linc)RNAs as novel genes
that contribute to cancer initiation, progression and metastasis
that contribute to cancer initiation, progression and metastasis
lincRNAs and epigenetics: 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 previously discovered human lincRNAs and 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, and their roles in human disease.
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, and their roles in human disease.
RNA in situ Hybridization of Human lincRNAs
Many lincRNAs associate with epigenetic-modifying complexes
lincRNAs are involved in various biological functions
Read more here:
We build on our previous discoveries: