1. Angiopoietin receptor TEK mutations underlie primary congenital glaucoma with variable expressivity.

    Journal of Clinical Investigation 126(7):2575 (2016) PMID 27270174 PMCID PMC4922711

    Primary congenital glaucoma (PCG) is a devastating eye disease and an important cause of childhood blindness worldwide. In PCG, defects in the anterior chamber aqueous humor outflow structures of the eye result in elevated intraocular pressure (IOP); however, the genes and molecular mechanisms i...
  2. NOTUM is a potential pharmacodynamic biomarker of Wnt pathway inhibition.

    Oncotarget 7(11):12386 (2016) PMID 26848981 PMCID PMC4914292

    Activation of Wnt signaling due to Wnt overexpression or mutations of Wnt pathway components is associated with various cancers. Blocking Wnt secretion by inhibiting PORCN enzymatic activity has shown efficacy in a subset of cancers with elevated Wnt signaling. Predicting response to upstream Wn...
  3. TEX11 is mutated in infertile men with azoospermia and regulates genome-wide recombination rates in mouse.

    Embo Molecular Medicine 7(9):1198 (2015) PMID 26136358 PMCID PMC4568952

    Genome-wide recombination is essential for genome stability, evolution, and speciation. Mouse Tex11, an X-linked meiosis-specific gene, promotes meiotic recombination and chromosomal synapsis. Here, we report that TEX11 is mutated in infertile men with non-obstructive azoospermia and that an ana...
  4. Regulatory crosstalk between lineage-survival oncogenes KLF5, GATA4 and GATA6 cooperatively promotes gastric cancer development.

    Gut 64(5):707 (2015) PMID 25053715

    Gastric cancer (GC) is a deadly malignancy for which new therapeutic strategies are needed. Three transcription factors, KLF5, GATA4 and GATA6, have been previously reported to exhibit genomic amplification in GC. We sought to validate these findings, investigate how these factors function to pr...
  5. High-depth sequencing of over 750 genes supports linear progression of primary tumors and metastases in most patients with liver-limited metastatic colorectal cancer.

    Genome Biology 16(1):32 (2015) PMID 25808843 PMCID PMC4365969

    Colorectal cancer with metastases limited to the liver (liver-limited mCRC) is a distinct clinical subset characterized by possible cure with surgery. We performed high-depth sequencing of over 750 cancer-associated genes and copy number profiling in matched primary, metastasis and normal tissue...
  6. Mutational landscapes of tongue carcinoma reveal recurrent mutations in genes of therapeutic and prognostic relevance.

    Genome Medicine 7(1):98 (2015) PMID 26395002 PMCID PMC4580363

    Carcinoma of the oral tongue (OTSCC) is the most common malignancy of the oral cavity, characterized by frequent recurrence and poor survival. The last three decades has witnessed a change in the OTSCC epidemiological profile, with increasing incidence in younger patients, females and never-smok...
  7. Sequencing the mouse Y chromosome reveals convergent gene acquisition and amplification on both sex chromosomes.

    Cell 159(4):800 (2014) PMID 25417157 PMCID PMC4260969

    We sequenced the MSY (male-specific region of the Y chromosome) of the C57BL/6J strain of the laboratory mouse Mus musculus. In contrast to theories that Y chromosomes are heterochromatic and gene poor, the mouse MSY is 99.9% euchromatic and contains about 700 protein-coding genes. Only 2% of th...
  8. Mammalian Y chromosomes retain widely expressed dosage-sensitive regulators.

    Nature 508(7497):494 (2014) PMID 24759411 PMCID PMC4139287

    The human X and Y chromosomes evolved from an ordinary pair of autosomes, but millions of years ago genetic decay ravaged the Y chromosome, and only three per cent of its ancestral genes survived. We reconstructed the evolution of the Y chromosome across eight mammals to identify biases in gene ...
  9. Massively parallel sequencing of patients with intellectual disability, congenital anomalies and/or autism spectrum disorders with a targeted gene panel.

    PLoS ONE 9(4):e93409 (2014) PMID 24690944 PMCID PMC3972136

    Developmental delay and/or intellectual disability (DD/ID) affects 1-3% of all children. At least half of these are thought to have a genetic etiology. Recent studies have shown that massively parallel sequencing (MPS) using a targeted gene panel is particularly suited for diagnostic testing for...
  10. Regionally-specified second trimester fetal neural stem cells reveals differential neurogenic programming.

    PLoS ONE 9(9):e105985 (2014) PMID 25181041 PMCID PMC4152177

    Neural stem/progenitor cells (NSC) have the potential for treatment of a wide range of neurological diseases such as Parkinson Disease and multiple sclerosis. Currently, NSC have been isolated only from hippocampus and subventricular zone (SVZ) of the adult brain. It is not known whether NSC can...
  11. Nanoscale chromatin profiling of gastric adenocarcinoma reveals cancer-associated cryptic promoters and somatically acquired regulatory elements.

    Nature Communications 5:4361 (2014) PMID 25008978

    Chromatin alterations are fundamental hallmarks of cancer. To study chromatin alterations in primary gastric adenocarcinomas, we perform nanoscale chromatin immunoprecipitation sequencing of multiple histone modifications in five gastric cancers and matched normal tissues. We identify hundreds o...
  12. Mutations inSCO2Are Associated with Autosomal-Dominant High-Grade Myopia

    The American Journal of Human Genetics 92(5):820 (2013) PMID 23643385 PMCID PMC3644634

    Myopia, or near-sightedness, is an ocular refractive error of unfocused image quality in front of the retinal plane. Individuals with high-grade myopia (dioptric power greater than −6.00) are predisposed to ocular morbidities such as glaucoma, retinal detachment, and myopic maculopathy...
  13. CYP1B1, MYOC, and LTBP2 mutations in primary congenital glaucoma patients in the United States.

    American Journal of Ophthalmology 155(3):508 (2013) PMID 23218701 PMCID PMC3736560

    To screen primary congenital glaucoma patients in the United States for sequence variants within the CYP1B1, LTBP2, and MYOC genes using Sanger and whole exome sequencing. Retrospective case-control study. Fifty-seven primary congenital glaucoma patients (47 families), 71 unaffected family membe...
  14. mTORC1 inhibition restricts inflammation-associated gastrointestinal tumorigenesis in mice.

    Journal of Clinical Investigation 123(2):767 (2013) PMID 23321674 PMCID PMC3561832

    Gastrointestinal cancers are frequently associated with chronic inflammation and excessive secretion of IL-6 family cytokines, which promote tumorigenesis through persistent activation of the GP130/JAK/STAT3 pathway. Although tumor progression can be prevented by genetic ablation of Stat3 in mic...
  15. Host cell transcriptome profile during wild-type and attenuated dengue virus infection.

    PLoS Neglected Tropical Diseases 7(3):e2107 (2013) PMID 23516652 PMCID PMC3597485

    Dengue viruses 1-4 (DENV1-4) rely heavily on the host cell machinery to complete their life cycle, while at the same time evade the host response that could restrict their replication efficiency. These requirements may account for much of the broad gene-level changes to the host transcriptome up...
  16. Methylation subtypes and large-scale epigenetic alterations in gastric cancer.

    Science Translational Medicine 4(156):156ra140 (2012) PMID 23076357

    Epigenetic alterations are fundamental hallmarks of cancer genomes. We surveyed the landscape of DNA methylation alterations in gastric cancer by analyzing genome-wide CG dinucleotide (CpG) methylation profiles of 240 gastric cancers (203 tumors and 37 cell lines) and 94 matched normal gastric t...
  17. TP53 genomic status regulates sensitivity of gastric cancer cells to the histone methylation inhibitor 3-deazaneplanocin A (DZNep).

    Clinical Cancer Research 18(15):4201 (2012) PMID 22675170

    DZNep (3-deazaneplanocin A) depletes EZH2, a critical component of polycomb repressive complex 2 (PRC2), which is frequently deregulated in cancer. Despite exhibiting promising anticancer activity, the specific genetic determinants underlying DZNep responsiveness in cancer cells remain largely u...
  18. Janus kinase 3-activating mutations identified in natural killer/T-cell lymphoma.

    Cancer Discovery 2(7):591 (2012) PMID 22705984

    The molecular pathogenesis of natural killer/T-cell lymphoma (NKTCL) is not well understood. We conducted whole-exome sequencing and identified Janus kinase 3 (JAK3) somatic-activating mutations (A572V and A573V) in 2 of 4 patients with NKTCLs. Further validation of the prevalence of JAK3 mutati...
  19. Exome sequencing of liver fluke-associated cholangiocarcinoma.

    Nature Genetics 44(6):690 (2012) PMID 22561520

    Opisthorchis viverrini-related cholangiocarcinoma (CCA), a fatal bile duct cancer, is a major public health concern in areas endemic for this parasite. We report here whole-exome sequencing of eight O. viverrini-related tumors and matched normal tissue. We identified and validated 206 somatic mu...
  20. A comprehensive survey of genomic alterations in gastric cancer reveals systematic patterns of molecular exclusivity and co-occurrence among distinct therapeutic targets.

    Gut 61(5):673 (2012) PMID 22315472 PMCID PMC3322587

    Gastric cancer is a major gastrointestinal malignancy for which targeted therapies are emerging as treatment options. This study sought to identify the most prevalent molecular targets in gastric cancer and to elucidate systematic patterns of exclusivity and co-occurrence among these targets, th...