Frazer Lab - UCSD
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Identification of pre-leukaemic haematopoietic stem cells in acute leukaemia.

Shlush, Liran I Zandi, Sasan Mitchell, Amanda Chen, Weihsu Claire Brandwein, Joseph M Gupta, Vikas Kennedy, James A Schimmer, Aaron D Schuh, Andre C Yee, Karen W ...

Published in Nature

In acute myeloid leukaemia (AML), the cell of origin, nature and biological consequences of initiating lesions, and order of subsequent mutations remain poorly understood, as AML is typically diagnosed without observation of a pre-leukaemic phase. Here, highly purified haematopoietic stem cells (HSCs), progenitor and mature cell fractions from the ...

Whole genome sequencing of Ethiopian highlanders reveals conserved hypoxia tolerance genes PDF available through Get Fulltext Research

Udpa, Nitin Ronen, Roy Zhou, Dan Liang, Junbin Stobdan, Tsering Appenzeller, Otto Yin, Ye Du, Yuanping Guo, Lixia Cao, Rui ...

Published in Genome Biology

BackgroundAlthough it has long been proposed that genetic factors contribute to adaptation to high altitude, such factors remain largely unverified. Recent advances in high-throughput sequencing have made it feasible to analyze genome-wide patterns of genetic variation in human populations. Since traditionally such studies surveyed only a small fra...

Genetic ancestry of participants in the National Children’s Study PDF available through Get Fulltext Research

Smith, Erin N Jepsen, Kristen Arias, Angelo D Shepard, Peter J Chambers, Christina D Frazer, Kelly A

Published in Genome Biology

BackgroundThe National Children’s Study (NCS) is a prospective epidemiological study in the USA tasked with identifying a nationally representative sample of 100,000 children, and following them from their gestation until they are 21 years of age. The objective of the study is to measure environmental and genetic influences on growth, development, ...

Evaluation of ultra-deep targeted sequencing for personalized breast cancer care PDF available through Get Fulltext Research

Harismendy, Olivier Schwab, Richard B Alakus, Hakan Yost, Shawn E Matsui, Hiroko Hasteh, Farnaz Wallace, Anne M Park, Hannah L Madlensky, Lisa Parker, Barbara ...

Published in Breast Cancer Research

IntroductionThe increasing number of targeted therapies, together with a deeper understanding of cancer genetics and drug response, have prompted major healthcare centers to implement personalized treatment approaches relying on high-throughput tumor DNA sequencing. However, the optimal way to implement this transformative methodology is not yet cl...

Identification of liver cancer progenitors whose malignant progression depends on autocrine IL-6 signaling. PDF available through Get Fulltext Research

He, Guobin Dhar, Debanjan Nakagawa, Hayato Font-Burgada, Joan Ogata, Hisanobu Jiang, Yuhong Shalapour, Shabnam Seki, Ekihiro Yost, Shawn E Jepsen, Kristen ...

Published in Cell

Hepatocellular carcinoma (HCC) is a slowly developing malignancy postulated to evolve from premalignant lesions in chronically damaged livers. However, it was never established that premalignant lesions actually contain tumor progenitors that give rise to cancer. Here, we describe isolation and characterization of HCC progenitor cells (HcPCs) from ...

Whole-Genome Sequencing Uncovers the Genetic Basis of Chronic Mountain Sickness in Andean Highlanders PDF available through Get Fulltext Research

Zhou, Dan Udpa, Nitin Ronen, Roy Stobdan, Tsering Liang, Junbin Appenzeller, Otto Zhao, Huiwen W. Yin, Yi Du, Yuanping Guo, Lixia ...

Published in The American Journal of Human Genetics

The hypoxic conditions at high altitudes present a challenge for survival, causing pressure for adaptation. Interestingly, many high-altitude denizens (particularly in the Andes) are maladapted, with a condition known as chronic mountain sickness (CMS) or Monge disease. To decode the genetic basis of this disease, we sequenced and compared the whol...

ADAR1 promotes malignant progenitor reprogramming in chronic myeloid leukemia.

Jiang, Qingfei Crews, Leslie A Barrett, Christian L Chun, Hye-Jung Court, Angela C Isquith, Jane M Zipeto, Maria A Goff, Daniel J Minden, Mark Sadarangani, Anil ...

Published in Proceedings of the National Academy of Sciences of the United States of America

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...

Transcriptome sequencing of tumor subpopulations reveals a spectrum of therapeutic options for squamous cell lung cancer...

Barrett, Christian L Schwab, Richard B Jung, HyunChul Crain, Brian Goff, Daniel J Jamieson, Catriona H M Thistlethwaite, Patricia A Harismendy, Olivier Carson, Dennis A Frazer, Kelly A ...

Published in PloS one

The only therapeutic options that exist for squamous cell lung carcinoma (SCC) are standard radiation and cytotoxic chemotherapy. Cancer stem cells (CSCs) are hypothesized to account for therapeutic resistance, suggesting that CSCs must be specifically targeted. Here, we analyze the transcriptome of CSC and non-CSC subpopulations by RNA-seq to iden...

Detection of low prevalence somatic mutations in solid tumors with ultra-deep targeted sequencing PDF available through Get Fulltext Research

Harismendy, Olivier Schwab, Richard B Bao, Lei Olson, Jeff Rozenzhak, Sophie Kotsopoulos, Steve K Pond, Stephanie Crain, Brian Chee, Mark S Messer, Karen ...

Published in Genome Biology

Ultra-deep targeted sequencing (UDT-Seq) can identify subclonal somatic mutations in tumor samples. Early assays' limited breadth and depth restrict their clinical utility. Here, we target 71 kb of mutational hotspots in 42 cancer genes. We present novel methods enhancing both laboratory workflow and mutation detection. We evaluate UDT-Seq true sen...

Sensitive gene fusion detection using ambiguously mapping RNA-Seq read pairs.

Kinsella, Marcus Harismendy, Olivier Nakano, Masakazu Frazer, Kelly A Bafna, Vineet

Published in Bioinformatics (Oxford, England)

Paired-end whole transcriptome sequencing provides evidence for fusion transcripts. However, due to the repetitiveness of the transcriptome, many reads have multiple high-quality mappings. Previous methods to find gene fusions either ignored these reads or required additional longer single reads. This can obscure up to 30% of fusions and unnecessar...

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