Faculty

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Timothy J Triche, MD, PhD
Professor of Pathology
Pediatrics
CHL Mail Stop 43 Off Campus Los Angeles
+1 323 361 4516

Overview

My research focuses on genetic aspects of cancer biology and their biologic consequences. Current research emphasizes whole genome approaches to gene expression profiling and genomic polymorphisms using DNA microarrays and software developed by our group to analyze this data. Laboratory studies typically utilize tumor cell lines expressing transfected genes, or with silenced genes. Gene targets and biologically active small molecules are often analyzed in biologic context by these same methods. Clinical correlative studies utilize tumor tissue with linked clinical data. Recently, these methods have been applied to studies of age related macular degeneration, as part of the Beckman Macular Research Center at the Doheny Eye Institute, Keck School of Medicine.

Publications

Preprocessing, normalization and integration of the Illumina HumanMethylationEPIC array with minfi. Bioinformatics. 2016 Dec 28. View in: PubMed

A Rapid and Sensitive Next-Generation Sequencing Method to Detect RB1 Mutations Improves Care for Retinoblastoma Patients and Their Families. J Mol Diagn. 2016 Jul; 18(4):480-93. View in: PubMed

Synergisitic and Antagonistic AML Cell Type-specific Responses to 5-Aza-2-deoxycitidine and 1-h-D-Arabinofuranoside. Anticancer Res. 2016 Feb; 36(2):691-6. View in: PubMed

Clinical Application of Prognostic Gene Expression Signature in Fusion Gene-Negative Rhabdomyosarcoma: A Report from the Children's Oncology Group. Clin Cancer Res. 2015 Oct 15; 21(20):4733-9. View in: PubMed

Insulin-like Growth Factor 2 Gene Expression Molecularly Differentiates Pleuropulmonary Blastoma and Embryonal Rhabdomyosarcoma. J Pediatr Hematol Oncol. 2015 Aug; 37(6):e356-60. View in: PubMed

Comprehensive, Integrative Genomic Analysis of Diffuse Lower-Grade Gliomas. N Engl J Med. 2015 Jun 25; 372(26):2481-98. View in: PubMed

Gene Expression Profiling of Ewing Sarcoma Tumors Reveals the Prognostic Importance of Tumor-Stromal Interactions: A Report from the Children's Oncology Group. J Pathol Clin Res. 2015 Apr; 1(2):83-94. View in: PubMed

Activity of MM-398, Nanoliposomal Irinotecan (nal-IRI), in Ewing's Family Tumor Xenografts Is Associated with High Exposure of Tumor to Drug and High SLFN11 Expression. Clin Cancer Res. 2015 Mar 1; 21(5):1139-50. View in: PubMed

Epigenetic reprogramming and re-differentiation of a Ewing sarcoma cell line. Front Cell Dev Biol. 2015; 3:15. View in: PubMed

Discovery and validation of novel expression signature for postcystectomy recurrence in high-risk bladder cancer. J Natl Cancer Inst. 2014 Nov; 106(11). View in: PubMed

The Genomic Landscape of the Ewing Sarcoma Family of Tumors Reveals Recurrent STAG2 Mutation. PLoS Genet. 2014 Jul; 10(7):e1004475. View in: PubMed

DrugPath: a database for academic investigators to match oncology molecular targets with drugs in development. Cancer Chemother Pharmacol. 2014 May; 73(5):1089-93. View in: PubMed

Reprogramming of the human intestinal epigenome by surgical tissue transposition. Genome Res. 2014 Apr; 24(4):545-53. View in: PubMed

Characterizing the genetic basis of methylome diversity in histologically normal human lung tissue. Nat Commun. 2014; 5:3365. View in: PubMed

The long noncoding RNA SChLAP1 promotes aggressive prostate cancer and antagonizes the SWI/SNF complex. Nat Genet. 2013 Nov; 45(11):1392-8. View in: PubMed

TDP1 and PARP1 deficiency are cytotoxic to rhabdomyosarcoma cells. Mol Cancer Res. 2013 Oct; 11(10):1179-92. View in: PubMed

Whole-transcriptome profiling of thyroid nodules identifies expression-based signatures for accurate thyroid cancer diagnosis. J Clin Endocrinol Metab. 2013 Oct; 98(10):4072-9. View in: PubMed

T lymphocyte abnormalities in juvenile systemic sclerosis patients. Clin Immunol. 2013 Oct; 149(1):146-55. View in: PubMed

A novel algorithm for simplification of complex gene classifiers in cancer. Cancer Res. 2013 Sep 15; 73(18):5625-32. View in: PubMed

PAX-FOXO1 fusion status drives unfavorable outcome for children with rhabdomyosarcoma: a children's oncology group report. Pediatr Blood Cancer. 2013 Sep; 60(9):1411-7. View in: PubMed

ERBB4 confers metastatic capacity in Ewing sarcoma. EMBO Mol Med. 2013 Jul; 5(7):1019-34. View in: PubMed

Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia. N Engl J Med. 2013 May 30; 368(22):2059-74. View in: PubMed

Low-level processing of Illumina Infinium DNA Methylation BeadArrays. Nucleic Acids Res. 2013 Apr; 41(7):e90. View in: PubMed

Characterization and Drug Resistance Patterns of Ewing's Sarcoma Family Tumor Cell Lines. PLoS One. 2013; 8(12):e80060. View in: PubMed

FOXM1 is an oncogenic mediator in Ewing Sarcoma. PLoS One. 2013; 8(1):e54556. View in: PubMed

Discovery and validation of a prostate cancer genomic classifier that predicts early metastasis following radical prostatectomy. PLoS One. 2013; 8(6):e66855. View in: PubMed

Mediators of receptor tyrosine kinase activation in infantile fibrosarcoma: a Children's Oncology Group study. J Pathol. 2012 Sep; 228(1):119-30. View in: PubMed

TARGETgene: A Tool for Identification of Potential Therapeutic Targets in Cancer. PLoS One. 2012; 7(8):e43305. View in: PubMed

Genomic "Dark Matter" in Prostate Cancer: Exploring the Clinical Utility of ncRNA as Biomarkers. Front Genet. 2012; 3:23. View in: PubMed

Influence of RNA Labeling on Expression Profiling of MicroRNAs. J Mol Diagn. 2012 Jan; 14(1):12-21. View in: PubMed

A central role for long non-coding RNA in cancer. Front Genet. 2012; 3:17. View in: PubMed

Enhanced growth inhibition of osteosarcoma by cytotoxic polymerized liposomal nanoparticles targeting the alcam cell surface receptor. Sarcoma. 2012; 2012:126906. View in: PubMed

Transcriptome-wide detection of differentially expressed coding and non-coding transcripts and their clinical significance in prostate cancer. J Oncol. 2012; 2012:541353. View in: PubMed

An epigenomic mechanism in retinoblastoma: the end of the story? Genome Med. An epigenomic mechanism in retinoblastoma: the end of the story? Genome Med. 2012; 4(2):15. View in: PubMed

Prognostic significance and tumor biology of regional lymph node disease in patients with rhabdomyosarcoma: a report from the Children's Oncology Group. J Clin Oncol. 2011 Apr 1; 29(10):1304-11. View in: PubMed

Ewing tumors that do not overexpress BMI-1 are a distinct molecular subclass with variant biology: a report from the Children's Oncology Group. Clin Cancer Res. 2011 Jan 1; 17(1):56-66. View in: PubMed

Synthetic lethality screens reveal RPS6 and MST1R as modifiers of insulin-like growth factor-1 receptor inhibitor activity in childhood sarcomas. Cancer Res. 2010 Nov 1; 70(21):8770-81. View in: PubMed

Fusion-negative alveolar rhabdomyosarcoma: modification of risk stratification is premature. J Clin Oncol. 2010 Oct 10; 28(29):e587-8; author reply e589-90. View in: PubMed

Prkar1a is an osteosarcoma tumor suppressor that defines a molecular subclass in mice. J Clin Invest. 2010 Sep 1; 120(9):3310-25. View in: PubMed

Quantitative expression profiling in formalin-fixed paraffin-embedded samples by affymetrix microarrays. J Mol Diagn. 2010 Jul; 12(4):409-17. View in: PubMed

Inhibition of the insulin-like growth factor I receptor by epigallocatechin gallate blocks proliferation and induces the death of Ewing tumor cells. Mol Cancer Ther. 2010 May; 9(5):1396-407. View in: PubMed

Current treatment protocols have eliminated the prognostic advantage of type 1 fusions in Ewing sarcoma: a report from the Children's Oncology Group. J Clin Oncol. 2010 Apr 20; 28(12):1989-94. View in: PubMed

Prediction of human functional genetic networks from heterogeneous data using RVM-based ensemble learning. Bioinformatics. 2010 Mar 15; 26(6):807-13. View in: PubMed

Gene expression profiling for survival prediction in pediatric rhabdomyosarcomas: a report from the children's oncology group. J Clin Oncol. 2010 Mar 1; 28(7):1240-6. View in: PubMed

Loss of CAK phosphorylation of RAR{alpha} mediates transcriptional control of retinoid-induced cancer cell differentiation. FASEB J. 2010 Mar; 24(3):833-43. View in: PubMed

CD133 expression in chemo-resistant Ewing sarcoma cells. BMC Cancer. 2010; 10:116. View in: PubMed

The majority of total nuclear-encoded non-ribosomal RNA in a human cell is 'dark matter' un-annotated RNA. BMC Biol. 2010; 8:149. View in: PubMed

Small interfering RNA library screen of human kinases and phosphatases identifies polo-like kinase 1 as a promising new target for the treatment of pediatric rhabdomyosarcomas. Mol Cancer Ther. 2009 Nov; 8(11):3024-35. View in: PubMed

Functional genomic analysis of peripheral blood during early acute renal allograft rejection. Transplantation. 2009 Oct 15; 88(7):942-51. View in: PubMed

Whole blood genomic biomarkers of acute cardiac allograft rejection. J Heart Lung Transplant. 2009 Sep; 28(9):927-35. View in: PubMed

Translational activation of snail1 and other developmentally regulated transcription factors by YB-1 promotes an epithelial-mesenchymal transition. Cancer Cell. 2009 May 5; 15(5):402-15. View in: PubMed

Molecular classification of rhabdomyosarcoma--genotypic and phenotypic determinants of diagnosis: a report from the Children's Oncology Group. Am J Pathol. 2009 Feb; 174(2):550-64. View in: PubMed

Canine tumor cross-species genomics uncovers targets linked to osteosarcoma progression. BMC Genomics. 2009; 10:625. View in: PubMed

Extraosseous Ewing's sarcoma: 25 years later. J Clin Oncol. 2008 Sep 10; 26(26):4230-2. View in: PubMed

BMI-1 promotes ewing sarcoma tumorigenicity independent of CDKN2A repression. Cancer Res. 2008 Aug 15; 68(16):6507-15. View in: PubMed

Mouse mesenchymal stem cells expressing PAX-FKHR form alveolar rhabdomyosarcomas by cooperating with secondary mutations. Cancer Res. 2008 Aug 15; 68(16):6587-97. View in: PubMed

Molecular characterization of the pediatric preclinical testing panel. Clin Cancer Res. 2008 Jul 15; 14(14):4572-83. View in: PubMed

Sparse representation and Bayesian detection of genome copy number alterations from microarray data. Bioinformatics. 2008 Feb 1; 24(3):309-18. View in: PubMed

Hierarchical Bayes prioritization of marker associations from a genome-wide association scan for further investigation. Genet Epidemiol. 2007 Dec; 31(8):871-82. View in: PubMed

Intrinsic retinoic acid receptor alpha-cyclin-dependent kinase-activating kinase signaling involves coordination of the restricted proliferation and granulocytic differentiation of human hematopoietic stem cells. Stem Cells. 2007 Oct; 25(10):2628-37. View in: PubMed

Histone deacetylase 1 gene expression and sensitization of multidrug-resistant neuroblastoma cell lines to cytotoxic agents by depsipeptide. J Natl Cancer Inst. 2007 Jul 18; 99(14):1107-19. View in: PubMed

Correlation between histology and PAX/FKHR fusion status in alveolar rhabdomyosarcoma: a report from the Children's Oncology Group. Am J Surg Pathol. 2007 Jun; 31(6):895-901. View in: PubMed

E-cadherin cell-cell adhesion in ewing tumor cells mediates suppression of anoikis through activation of the ErbB4 tyrosine kinase. Cancer Res. 2007 Apr 1; 67(7):3094-105. View in: PubMed

Population-based study of early age-related macular degeneration: role of the complement factor H Y402H polymorphism in bilateral but not unilateral disease. Ophthalmology. 2007 Jan; 114(1):99-103. View in: PubMed

Urokinase-type Plasminogen Activator (uPA) is Inhibited with QLT0267 a Small Molecule Targeting Integrin-linked Kinase (ILK). Transl Oncogenomics. 2007; 2:85-97. View in: PubMed

Experimental comparison and evaluation of the Affymetrix exon and U133Plus2 GeneChip arrays. PLoS One. 2007; 2(9):e913. View in: PubMed

Retinoic acid induces leukemia cell G1 arrest and transition into differentiation by inhibiting cyclin-dependent kinase-activating kinase binding and phosphorylation of PML/RARalpha. FASEB J. 2006 Oct; 20(12):2142-4. View in: PubMed

Identification of a PAX-FKHR gene expression signature that defines molecular classes and determines the prognosis of alveolar rhabdomyosarcomas. Cancer Res. 2006 Jul 15; 66(14):6936-46. View in: PubMed

The homeoprotein six1 transcriptionally activates multiple protumorigenic genes but requires ezrin to promote metastasis. Cancer Res. 2006 Feb 15; 66(4):1982-9. View in: PubMed

Akt-mediated YB-1 phosphorylation activates translation of silent mRNA species. Mol Cell Biol. 2006 Jan; 26(1):277-92. View in: PubMed

The ETV6-NTRK3 chimeric tyrosine kinase suppresses TGF-beta signaling by inactivating the TGF-beta type II receptor. Proc Natl Acad Sci U S A. 2005 Nov 8; 102(45):16239-44. View in: PubMed

Sequence-specific knockdown of EWS-FLI1 by targeted, nonviral delivery of small interfering RNA inhibits tumor growth in a murine model of metastatic Ewing's sarcoma. Cancer Res. 2005 Oct 1; 65(19):8984-92. View in: PubMed

Expression profiles of osteosarcoma that can predict response to chemotherapy. Cancer Res. 2005 Sep 15; 65(18):8142-50. View in: PubMed

A nanoparticle-based model delivery system to guide the rational design of gene delivery to the liver. 2. In vitro and in vivo uptake results. Bioconjug Chem. 2005 Sep-Oct; 16(5):1071-80. View in: PubMed

EWS-FLI1 fusion protein up-regulates critical genes in neural crest development and is responsible for the observed phenotype of Ewing's family of tumors. Cancer Res. 2005 Jun 1; 65(11):4633-44. View in: PubMed

Affymetrix oligonucleotide analysis of gene expression in the injured heart. Methods Mol Med. 2005; 112:305-20. View in: PubMed

Lack of interferon response in animals to naked siRNAs. Nat Biotechnol. 2004 Dec; 22(12):1579-82. View in: PubMed

Retinoid-modulated MAT1 ubiquitination and CAK activity. FASEB J. 2004 Nov; 18(14):1734-6. View in: PubMed

Selective usage of D-Type cyclins by Ewing's tumors and rhabdomyosarcomas. Cancer Res. 2004 Sep 1; 64(17):6026-34. View in: PubMed

MAT1-modulated cyclin-dependent kinase-activating kinase activity cross-regulates neuroblastoma cell G1 arrest and neurite outgrowth. Cancer Res. 2004 May 1; 64(9):2977-83. View in: PubMed

Sensitivity and specificity of five abundance estimators for high-density oligonucleotide microarrays. Bioinformatics. 2004 May 1; 20(7):1060-5. View in: PubMed

Growth inhibition of breast epithelial cells by celecoxib is associated with upregulation of insulin-like growth factor binding protein-3 expression. Biochem Biophys Res Commun. 2004 Apr 2; 316(2):421-8. View in: PubMed

Genetic determinants of coxsackievirus B3 pathogenesis. Ann N Y Acad Sci. 2002 Dec; 975:169-79. View in: PubMed

Retinoid-induced G1 arrest and differentiation activation are associated with a switch to cyclin-dependent kinase-activating kinase hypophosphorylation of retinoic acid receptor alpha. J Biol Chem. 2002 Nov 8; 277(45):43369-76. View in: PubMed

Wang J, Barsky LW, Shum CH, Jong A, Weinberg KI, Collins SJ, Triche TJ, Wu L. Retinoid-induced G1 arrest and differentiation activation are associated with a switch to cyclan-dependent kinase-activating kanase hypophosphgrylation of retanoic acid receptor alpha. J Biod Chem. 2002 Nov 8; 277(45):43361-76. View in: PubMed

Genetic heterogeneity in the alveolar rhabdomyosarcoma subset without typical gene fusions. Cancer Res. 2002 Aug 15; 62(16):4704-10. View in: PubMed

cDNA microarray analysis of global gene expression in sarcomas. Curr Opin Oncol. 2002 Jul; 14(4):406-11. View in: PubMed

PAX3-FKHR and PAX7-FKHR gene fusions are prognostic indicators in alveolar rhabdomyosarcoma: a report from the children's oncology group. J Clin Oncol. 2002 Jun 1; 20(11):2672-9. View in: PubMed

Infectomics: genomics and proteomics of microbial infections. Funct Integr Genomics. 2002 Apr; 1(6):331-44. View in: PubMed

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