Christian Barrett

Reversion to an embryonic alternative splicing program enhances leukemia stem cell self-renewal.

Published in Proceedings of the National Academy of Sciences

Formative research suggests that a human embryonic stem cell-specific alternative splicing gene regulatory network, which is repressed by Muscleblind-like (MBNL) RNA binding proteins, is involved in cell reprogramming. In this study, RNA sequencing, splice isoform-specific quantitative RT-PCR, lentiviral transduction, and in vivo humanized mouse mo...

Transcriptome Sequencing of Tumor Subpopulations Reveals a Spectrum of Therapeutic Options for Squamous Cell Lung Cancer...

A Pan-BCL2 inhibitor renders bone-marrow-resident human leukemia stem cells sensitive to tyrosine kinase inhibition.

Published in Cell Stem Cell

Leukemia stem cells (LSCs) play a pivotal role in the resistance of chronic myeloid leukemia (CML) to tyrosine kinase inhibitors (TKIs) and its progression to blast crisis (BC), in part, through the alternative splicing of self-renewal and survival genes. To elucidate splice-isoform regulators of human BC LSC maintenance, we performed whole-transcr...

ADAR1 promotes malignant progenitor reprogramming in chronic myeloid leukemia.

Published in Proceedings of the National Academy of Sciences

The molecular etiology of human progenitor reprogramming into self-renewing leukemia stem cells (LSC) has remained elusive. Although DNA sequencing has uncovered spliceosome gene mutations that promote alternative splicing and portend leukemic transformation, isoform diversity also may be generated by RNA editing mediated by adenosine deaminase act...

An RNA editing fingerprint of cancer stem cell reprogramming.

Published in Journal of Translational Medicine

Systematic transcriptome analysis reveals tumor-specific isoforms for ovarian cancer diagnosis and therapy.

Published in Proceedings of the National Academy of Sciences

Tumor-specific molecules are needed across diverse areas of oncology for use in early detection, diagnosis, prognosis and therapy. Large and growing public databases of transcriptome sequencing data (RNA-seq) derived from tumors and normal tissues hold the potential of yielding tumor-specific molecules, but because the data are new they have not be...

Genetic and epigenetic profiling of CLL disease progression reveals limited somatic evolution and suggests a relationshi...

Published in Blood Cancer Journal

We examined genetic and epigenetic changes that occur during disease progression from indolent to aggressive forms of chronic lymphocytic leukemia (CLL) using serial samples from 27 patients. Analysis of DNA mutations grouped the leukemia cases into three categories: evolving (26%), expanding (26%) and static (47%). Thus, approximately three-quarte...

Transcriptome sequencing reveals potential mechanism of cryptic 3 splice site selection in SF3B1-mutated cancers.

Published in PLoS Computational Biology

Mutations in the splicing factor SF3B1 are found in several cancer types and have been associated with various splicing defects. Using transcriptome sequencing data from chronic lymphocytic leukemia, breast cancer and uveal melanoma tumor samples, we show that hundreds of cryptic 3 splice sites (3 SSs) are used in cancers with SF3B1 mutations. We ...