Hai Yan
Adjunct Professor of Pathology
Our research activities center on the molecular genetics and biology of cancer with a focus on the identification, characterization, and therapeutic targeting of driver mutations involved in the genesis and progression of brain cancers. Gliomas are the most common type of primary brain tumor. Through genomic studies, we have identified mutations in IDH1 and IDH2 in 70% of progressive malignant gliomas. These are somatic missense mutations that alter a conserved arginine residue and gain a neomorphic activity. A new metabolite produced by the glioma cells impacts on chromatin modulation and genome methylation. Malignant cells must maintain their telomeres. We identified several different tumor types exhibiting a high frequency of TERT promoter mutations, including several glioma subtypes. Conversely, we found a low frequency of TERT promoter mutations in many common epithelial tumors. In gliomas, we found that TERT promoter mutations were mutually exclusive with ATRX alterations, which are associated with activation of the ALT pathway for telomere maintenance. These findings show that TERT promoter mutations are frequent driver events in many human cancers, particularly those that arise from tissues with low rates of self-renewal. Our long-term goal is to develop a novel molecular-based glioma classification system and a targeted therapy on the basis of IDH1 and TERT mutations. To provide novel avenues for development of anticancer therapeutics, studies involving cell line and animal models, enzymatic study, metabolome and epigenome, are being investigated to determine the consequences of IDH1 and TERT mutations on cancer cells.
Current Appointments & Affiliations
- Adjunct Professor of Pathology, Pathology, Clinical Science Departments 2022
Contact Information
- 5833 Plainview Rd, Bethesda, MD 20817
- Duke Box 3156, Department of Pathology, Durham, NC 27710
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hai.yan@duke.edu
(301) 508-0881
- Background
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Education, Training, & Certifications
- Research Associate, Howard Hughes Institute, Johns Hopkins University 1997 - 2002
- Ph.D., Columbia University 1997
- M.D., Beijing Medical University (China) 1991
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Previous Appointments & Affiliations
- Member of the Duke Cancer Institute, Duke Cancer Institute, Institutes and Centers 2003 - 2022
- Professor of Pathology, Pathology, Clinical Science Departments 2012 - 2022
- Professor of Pharmacology and Cancer Biology, Pharmacology & Cancer Biology, Basic Science Departments 2013 - 2022
- Henry S. Friedman Distinguished Professor of Neuro-Oncology in the School of Medicine, Pathology, Clinical Science Departments 2014 - 2022
- Associate Professor of Pathology, Pathology, Clinical Science Departments 2011 - 2012
- Associate Professor of Pathology, Pathology, Clinical Science Departments 2009 - 2011
- Assistant Professor of Pathology, Pathology, Clinical Science Departments 2003 - 2009
- Instructor, Temporary of Pathology, Pathology, Clinical Science Departments 2003
- Recognition
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In the News
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JUN 2, 2014 -
JUN 1, 2014 Duke Today
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- Expertise
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Subject Headings
- Adaptor Proteins, Signal Transducing
- Adenocarcinoma
- Adenocarcinoma, Clear Cell
- Adenoma
- Adenosine Triphosphatases
- Adenosine Triphosphate
- Adipates
- Aged
- Aged, 80 and over
- Alcohol Oxidoreductases
- Alleles
- Alternative Splicing
- Amino Acid Sequence
- Animals
- Annexin A5
- Anoxia
- Antibodies
- Antibodies, Monoclonal
- Antigens, CD4
- Antimetabolites, Antineoplastic
- Antineoplastic Agents
- Antineoplastic Agents, Alkylating
- Arginine
- Astrocytes
- Astrocytoma
- Base Pair Mismatch
- Benzeneacetamides
- Binding Sites
- Blotting, Western
- Brain Neoplasms
- Burkitt Lymphoma
- Calpain
- Carcinoma, Neuroendocrine
- Carcinoma, Non-Small-Cell Lung
- Carcinoma, Small Cell
- Carcinoma, Squamous Cell
- Carmustine
- Catalytic Domain
- Cell Differentiation
- Cell Division
- Cell Growth Processes
- Cell Line
- Cell Line, Transformed
- Cell Line, Tumor
- Cell Nucleus
- Cell Proliferation
- Cell Transformation, Neoplastic
- Cells, Cultured
- Central Nervous System Neoplasms
- Cerebellar Neoplasms
- Cerebellum
- Chromatin
- Chromatin Assembly and Disassembly
- Chromatin Immunoprecipitation
- Chromosome Aberrations
- Chromosome Painting
- Chromosomes
- Chromosomes, Human, Pair 1
- Chromosomes, Human, Pair 19
- Chromosomes, Human, Pair 2
- Chromosomes, Human, Pair 9
- Cloning, Molecular
- Codon
- Codon, Nonsense
- Cohort Studies
- Colon
- Colorectal Neoplasms
- Computational Biology
- CpG Islands
- Cyclin-Dependent Kinase Inhibitor p18
- Cytoplasm
- DNA
- DNA Copy Number Variations
- DNA Helicases
- DNA Methylation
- DNA Mutational Analysis
- DNA Primers
- DNA Probes
- DNA Repair
- DNA, Complementary
- DNA, Neoplasm
- Dioxygenases
- Dipeptides
- Disease Progression
- Dogs
- Down-Regulation
- Drug Resistance, Neoplasm
- Endoplasmic Reticulum
- Energy Metabolism
- Enzyme Induction
- Enzyme Inhibitors
- Epigenesis, Genetic
- Epigenomics
- Escherichia coli
- Exons
- Female
- Fibrosarcoma
- Flow Cytometry
- Fluorescent Dyes
- Frameshift Mutation
- Gene Amplification
- Gene Deletion
- Gene Expression Profiling
- Gene Expression Regulation
- Gene Expression Regulation, Enzymologic
- Gene Expression Regulation, Neoplastic
- Gene Knockdown Techniques
- Gene Silencing
- Genes, APC
- Genes, Neoplasm
- Genes, Reporter
- Genes, Tumor Suppressor
- Genes, erbB-1
- Genes, myc
- Genetic Complementation Test
- Genetic Loci
- Genetic Techniques
- Genetic Variation
- Genetics, Medical
- Genome, Human
- Genome-Wide Association Study
- Genomics
- Genotype
- Germ-Line Mutation
- Glioblastoma
- Glioma
- Glucose
- Glutarates
- Glutathione Transferase
- Guanylate Cyclase
- HCT116 Cells
- Hematopoiesis
- Histidine
- Histone-Lysine N-Methyltransferase
- Histones
- Homeodomain Proteins
- Humans
- Hybridomas
- Hypoxia-Inducible Factor 1
- Imidazoles
- Immunoblotting
- Immunohistochemistry
- Immunoprecipitation
- In Situ Hybridization, Fluorescence
- Interferon Type I
- Interferon-alpha
- Interferon-gamma
- Isocitrate Dehydrogenase
- Isocitrates
- Janus Kinase 1
- Kaplan-Meier Estimate
- Karyotyping
- Ketoglutaric Acids
- Kruppel-Like Transcription Factors
- Lactates
- Leukemia, Myeloid, Acute
- Ligands
- Loss of Heterozygosity
- Lymphocytes
- Magnetics
- Male
- Medulloblastoma
- Melanoma
- Metabolome
- Methylation
- Methylene Blue
- Mice
- Mice, Inbred BALB C
- Mice, Nude
- Mice, Transgenic
- MicroRNAs
- Microsatellite Instability
- Microsatellite Repeats
- Microtubule-Associated Proteins
- Middle Aged
- Models, Biological
- Models, Molecular
- Molecular Sequence Data
- Moths
- MutS Homolog 2 Protein
- Mutagenesis, Site-Directed
- Mutant Proteins
- Mutation
- Mutation, Missense
- Neoplasm Grading
- Neoplasm Transplantation
- Neoplasms
- Neoplasms, Experimental
- Neural Stem Cells
- Oligodendroglioma
- Oncogenes
- Otx Transcription Factors
- Phenotype
- Phenylurea Compounds
- Phosphatidylinositol 3-Kinases
- Phosphoric Monoester Hydrolases
- Phosphotyrosine
- Physical Chromosome Mapping
- Point Mutation
- Polymerase Chain Reaction
- Polymorphism, Genetic
- Polymorphism, Single Nucleotide
- Procollagen-Proline Dioxygenase
- Prognosis
- Promoter Regions, Genetic
- Protein Biosynthesis
- Protein Conformation
- Protein Engineering
- Protein Kinases
- Protein Processing, Post-Translational
- Protein Structure, Tertiary
- Protein Tyrosine Phosphatase, Non-Receptor Type 13
- Protein Tyrosine Phosphatase, Non-Receptor Type 3
- Protein Tyrosine Phosphatases
- Protein-Tyrosine Kinases
- Proto-Oncogene Proteins
- RNA Interference
- RNA, Messenger
- RNA, Small Interfering
- Real-Time Polymerase Chain Reaction
- Receptor Protein-Tyrosine Kinases
- Receptor, Epidermal Growth Factor
- Receptor, Interferon alpha-beta
- Receptor, Notch2
- Receptor, trkC
- Receptor-Like Protein Tyrosine Phosphatases, Class 2
- Receptor-Like Protein Tyrosine Phosphatases, Class 5
- Receptors, Cell Surface
- Receptors, Cytokine
- Receptors, Interferon
- Recombinant Fusion Proteins
- Repressor Proteins
- Reverse Transcriptase Polymerase Chain Reaction
- Rhombencephalon
- Risk Factors
- S100 Proteins
- STAT1 Transcription Factor
- STAT2 Transcription Factor
- Saccharomyces cerevisiae
- Sequence Analysis, DNA
- Sequence Deletion
- Signal Transduction
- Spodoptera
- Stomach
- Stomach Neoplasms
- Streptolysins
- Sulfonamides
- Suppressor of Cytokine Signaling Proteins
- Survival Rate
- TYK2 Kinase
- Telomerase
- Telomere
- Templates, Genetic
- Tolonium Chloride
- Trans-Activators
- Transcription, Genetic
- Transfection
- Tretinoin
- Tumor Cells, Cultured
- Tumor Markers, Biological
- Tumor Stem Cell Assay
- Tumor Suppressor Protein p53
- Tumor Suppressor Proteins
- Tunicamycin
- Tyrosine
- Up-Regulation
- Xenograft Model Antitumor Assays
- Young Adult
- src Homology Domains
- Publications & Artistic Works
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Selected Publications
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Academic Articles
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Xu, Cheng, Heng Liu, Christopher J. Pirozzi, Lee H. Chen, Paula K. Greer, Bill H. Diplas, Liwei Zhang, Matthew S. Waitkus, Yiping He, and Hai Yan. “TP53 wild-type/PPM1D mutant diffuse intrinsic pontine gliomas are sensitive to a MDM2 antagonist.” Acta Neuropathol Commun 9, no. 1 (November 3, 2021): 178. https://doi.org/10.1186/s40478-021-01270-y.Full Text Link to Item
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Lee, Donghyun D., Martin Komosa, Sumedha Sudhaman, Ricardo Leão, Cindy H. Zhang, Joana D. Apolonio, Thomas Hermanns, et al. “Dual role of allele-specific DNA hypermethylation within the TERT promoter in cancer.” J Clin Invest 131, no. 21 (November 1, 2021). https://doi.org/10.1172/JCI146915.Full Text Link to Item
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Pirozzi, Christopher J., and Hai Yan. “The implications of IDH mutations for cancer development and therapy.” Nat Rev Clin Oncol 18, no. 10 (October 2021): 645–61. https://doi.org/10.1038/s41571-021-00521-0.Full Text Link to Item
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Waitkus, Matthew S., and Hai Yan. “Targeting Isocitrate Dehydrogenase Mutations in Cancer: Emerging Evidence and Diverging Strategies.” Clin Cancer Res 27, no. 2 (January 15, 2021): 383–88. https://doi.org/10.1158/1078-0432.CCR-20-1827.Full Text Link to Item
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Gromeier, Matthias, Michael C. Brown, Gao Zhang, Xiang Lin, Yeqing Chen, Zhi Wei, Nike Beaubier, et al. “Very low mutation burden is a feature of inflamed recurrent glioblastomas responsive to cancer immunotherapy.” Nat Commun 12, no. 1 (January 13, 2021): 352. https://doi.org/10.1038/s41467-020-20469-6.Full Text Open Access Copy Link to Item
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Pirozzi, Christopher J., and Hai Yan. “Hitting Gliomas When They Are Down: Exploiting IDH-Mutant Metabolic Vulnerabilities.” Cancer Discov 10, no. 11 (November 2020): 1629–31. https://doi.org/10.1158/2159-8290.CD-20-1215.Full Text Link to Item
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Wang, Zhaohui, Cheng Xu, Bill H. Diplas, Casey J. Moure, Chin-Pu Jason Chen, Lee H. Chen, Changzheng Du, et al. “Targeting Mutant PPM1D Sensitizes Diffuse Intrinsic Pontine Glioma Cells to the PARP Inhibitor Olaparib.” Molecular Cancer Research : Mcr 18, no. 7 (July 2020): 968–80. https://doi.org/10.1158/1541-7786.mcr-19-0507.Full Text
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Chen, Lee H., Changcun Pan, Bill H. Diplas, Cheng Xu, Landon J. Hansen, Yuliang Wu, Xin Chen, et al. “The integrated genomic and epigenomic landscape of brainstem glioma.” Nat Commun 11, no. 1 (June 17, 2020): 3077. https://doi.org/10.1038/s41467-020-16682-y.Full Text Link to Item
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Liang, Junbo, Hong Zhao, Bill H. Diplas, Song Liu, Jianmei Liu, Dingding Wang, Yan Lu, et al. “Genome-Wide CRISPR-Cas9 Screen Reveals Selective Vulnerability of ATRX-Mutant Cancers to WEE1 Inhibition.” Cancer Res 80, no. 3 (February 1, 2020): 510–23. https://doi.org/10.1158/0008-5472.CAN-18-3374.Full Text Link to Item
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Mattox, Austin K., Hai Yan, and Chetan Bettegowda. “The potential of cerebrospinal fluid-based liquid biopsy approaches in CNS tumors.” Neuro Oncol 21, no. 12 (December 17, 2019): 1509–18. https://doi.org/10.1093/neuonc/noz156.Full Text Link to Item
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Moure, Casey J., Bill H. Diplas, Lee H. Chen, Rui Yang, Christopher J. Pirozzi, Zhaohui Wang, Ivan Spasojevic, Matthew S. Waitkus, Yiping He, and Hai Yan. “CRISPR Editing of Mutant IDH1 R132H Induces a CpG Methylation-Low State in Patient-Derived Glioma Models of G-CIMP.” Mol Cancer Res 17, no. 10 (October 2019): 2042–50. https://doi.org/10.1158/1541-7786.MCR-19-0309.Full Text Link to Item
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Du, Changzheng, Landon J. Hansen, Simranjit X. Singh, Feiyifan Wang, Ran Sun, Casey J. Moure, Kristen Roso, Paula K. Greer, Hai Yan, and Yiping He. “A PRMT5-RNF168-SMURF2 Axis Controls H2AX Proteostasis.” Cell Rep 28, no. 12 (September 17, 2019): 3199-3211.e5. https://doi.org/10.1016/j.celrep.2019.08.031.Full Text Link to Item
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Liu, Yang, Austin B. Carpenter, Christopher J. Pirozzi, Hsiangkuo Yuan, Matthew S. Waitkus, Zhengyuan Zhou, Landon Hansen, et al. “Non-invasive sensitive brain tumor detection using dual-modality bioimaging nanoprobe.” Nanotechnology 30, no. 27 (July 5, 2019): 275101. https://doi.org/10.1088/1361-6528/ab0e9c.Full Text Link to Item
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Hansen, Landon J., Ran Sun, Rui Yang, Simranjit X. Singh, Lee H. Chen, Christopher J. Pirozzi, Casey J. Moure, et al. “MTAP Loss Promotes Stemness in Glioblastoma and Confers Unique Susceptibility to Purine Starvation.” Cancer Res 79, no. 13 (July 1, 2019): 3383–94. https://doi.org/10.1158/0008-5472.CAN-18-1010.Full Text Link to Item
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Baig, Shahid Mahmood, Ambrin Fatima, Muhammad Tariq, Tahir Naeem Khan, Zafar Ali, Mohammad Faheem, Humera Mahmood, et al. “Hereditary brain tumor with a homozygous germline mutation in PMS2: pedigree analysis and prenatal screening in a family with constitutional mismatch repair deficiency (CMMRD) syndrome.” Fam Cancer 18, no. 2 (April 2019): 261–65. https://doi.org/10.1007/s10689-018-0112-4.Full Text Link to Item
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Lee, Donghyun D., Ricardo Leão, Martin Komosa, Marco Gallo, Cindy H. Zhang, Tatiana Lipman, Marc Remke, et al. “DNA hypermethylation within TERT promoter upregulates TERT expression in cancer.” J Clin Invest 129, no. 4 (April 1, 2019): 1801. https://doi.org/10.1172/JCI128527.Full Text Link to Item
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Qu, Chunfeng, Yuting Wang, Pei Wang, Kun Chen, Minjie Wang, Hongmei Zeng, Jianquan Lu, et al. “Detection of early-stage hepatocellular carcinoma in asymptomatic HBsAg-seropositive individuals by liquid biopsy.” Proc Natl Acad Sci U S A 116, no. 13 (March 26, 2019): 6308–12. https://doi.org/10.1073/pnas.1819799116.Full Text Link to Item
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Diplas, Bill H., Heng Liu, Rui Yang, Landon J. Hansen, Alexis L. Zachem, Fangping Zhao, Darell D. Bigner, et al. “Sensitive and rapid detection of TERT promoter and IDH mutations in diffuse gliomas.” Neuro Oncol 21, no. 4 (March 18, 2019): 440–50. https://doi.org/10.1093/neuonc/noy167.Full Text Link to Item
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Pan, Changcun, Bill H. Diplas, Xin Chen, Yuliang Wu, Xiong Xiao, Liping Jiang, Yibo Geng, et al. “Molecular profiling of tumors of the brainstem by sequencing of CSF-derived circulating tumor DNA.” Acta Neuropathol 137, no. 2 (February 2019): 297–306. https://doi.org/10.1007/s00401-018-1936-6.Full Text Link to Item
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Lee, Donghyun D., Ricardo Leão, Martin Komosa, Marco Gallo, Cindy H. Zhang, Tatiana Lipman, Marc Remke, et al. “DNA hypermethylation within TERT promoter upregulates TERT expression in cancer.” J Clin Invest 129, no. 1 (January 2, 2019): 223–29. https://doi.org/10.1172/JCI121303.Full Text Link to Item
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Pan, Chang-Cun, Jia Liu, Jie Tang, Xin Chen, Fang Chen, Yu-Liang Wu, Yi-Bo Geng, et al. “A machine learning-based prediction model of H3K27M mutations in brainstem gliomas using conventional MRI and clinical features.” Radiother Oncol 130 (January 2019): 172–79. https://doi.org/10.1016/j.radonc.2018.07.011.Full Text Link to Item
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Lei, Kefeng, Ran Sun, Lee H. Chen, Bill H. Diplas, Casey J. Moure, Wenzhe Wang, Landon J. Hansen, et al. “Mutant allele quantification reveals a genetic basis for TP53 mutation-driven castration resistance in prostate cancer cells.” Sci Rep 8, no. 1 (August 21, 2018): 12507. https://doi.org/10.1038/s41598-018-30062-z.Full Text Link to Item
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Waitkus, Matthew S., Bill H. Diplas, and Hai Yan. “Biological Role and Therapeutic Potential of IDH Mutations in Cancer.” Cancer Cell 34, no. 2 (August 13, 2018): 186–95. https://doi.org/10.1016/j.ccell.2018.04.011.Full Text Link to Item
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Chen, Jianhua, Xuemin Jian, Siyu Deng, Zengyi Ma, Xuefei Shou, Yue Shen, Qilin Zhang, et al. “Identification of recurrent USP48 and BRAF mutations in Cushing's disease.” Nat Commun 9, no. 1 (August 9, 2018): 3171. https://doi.org/10.1038/s41467-018-05275-5.Full Text Link to Item
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Chitneni, Satish K., Hai Yan, and Michael R. Zalutsky. “Synthesis and Evaluation of a 18F-Labeled Triazinediamine Analogue for Imaging Mutant IDH1 Expression in Gliomas by PET.” Acs Med Chem Lett 9, no. 7 (July 12, 2018): 606–11. https://doi.org/10.1021/acsmedchemlett.7b00478.Full Text Link to Item
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Pirozzi, Christopher J., and Hai Yan. “Improved grading of IDH-mutated astrocytic gliomas.” Nat Rev Neurol 14, no. 7 (July 2018): 383–84. https://doi.org/10.1038/s41582-018-0019-6.Full Text Link to Item
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Diplas, Bill H., Xujun He, Jacqueline A. Brosnan-Cashman, Heng Liu, Lee H. Chen, Zhaohui Wang, Casey J. Moure, et al. “The genomic landscape of TERT promoter wildtype-IDH wildtype glioblastoma.” Nat Commun 9, no. 1 (May 25, 2018): 2087. https://doi.org/10.1038/s41467-018-04448-6.Full Text Link to Item
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Chitneni, Satish K., Zachary J. Reitman, Rebecca Spicehandler, David M. Gooden, Hai Yan, and Michael R. Zalutsky. “Synthesis and evaluation of radiolabeled AGI-5198 analogues as candidate radiotracers for imaging mutant IDH1 expression in tumors.” Bioorg Med Chem Lett 28, no. 4 (February 15, 2018): 694–99. https://doi.org/10.1016/j.bmcl.2018.01.015.Full Text Link to Item
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Tiburcio, Patricia D. B., Bing Xiao, Shauna Berg, Sydney Asper, Sean Lyne, Yan Zhang, Xingen Zhu, Hai Yan, and L Eric Huang. “Functional requirement of a wild-type allele for mutant IDH1 to suppress anchorage-independent growth through redox homeostasis.” Acta Neuropathol 135, no. 2 (February 2018): 285–98. https://doi.org/10.1007/s00401-017-1800-0.Full Text Link to Item
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Mao, K., and H. Yan. “Precise medicine and individualized diagnosis and treatment of bladder cancer.” Chinese Journal of Cancer Biotherapy 25, no. 1 (January 1, 2018): 17–22. https://doi.org/10.3872/j.issn.1007-385x.2018.01.003.Full Text
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Waitkus, Matthew S., Christopher J. Pirozzi, Casey J. Moure, Bill H. Diplas, Landon J. Hansen, Austin B. Carpenter, Rui Yang, et al. “Adaptive Evolution of the GDH2 Allosteric Domain Promotes Gliomagenesis by Resolving IDH1R132H-Induced Metabolic Liabilities.” Cancer Res 78, no. 1 (January 1, 2018): 36–50. https://doi.org/10.1158/0008-5472.CAN-17-1352.Full Text Link to Item
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Yang, Rui, Lee H. Chen, Landon J. Hansen, Austin B. Carpenter, Casey J. Moure, Heng Liu, Christopher J. Pirozzi, et al. “Cic Loss Promotes Gliomagenesis via Aberrant Neural Stem Cell Proliferation and Differentiation.” Cancer Res 77, no. 22 (November 15, 2017): 6097–6108. https://doi.org/10.1158/0008-5472.CAN-17-1018.Full Text Link to Item
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Xu, Cheng, Xiaoqing Liu, Yibo Geng, Qingran Bai, Changcun Pan, Yu Sun, Xin Chen, et al. “Patient-derived DIPG cells preserve stem-like characteristics and generate orthotopic tumors.” Oncotarget 8, no. 44 (September 29, 2017): 76644–55. https://doi.org/10.18632/oncotarget.19656.Full Text Link to Item
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Xu, Cheng, Xiaoqing Liu, Yibo Geng, Qingran Bai, Changcun Pan, Yu Sun, Xin Chen, et al. “Patient-derived DIPG cells preserve stem-like characteristics and generate orthotopic tumors.” Oncotarget, July 28, 2017. https://doi.org/10.18632/oncotarget.19656.Full Text Link to Item
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Zhang, Qilin, Cheng Peng, Jianping Song, Yichao Zhang, Jianhua Chen, Zhijian Song, Xuefei Shou, et al. “Germline Mutations in CDH23, Encoding Cadherin-Related 23, Are Associated with Both Familial and Sporadic Pituitary Adenomas.” Am J Hum Genet 100, no. 5 (May 4, 2017): 817–23. https://doi.org/10.1016/j.ajhg.2017.03.011.Full Text Link to Item
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Pirozzi, Christopher J., Austin B. Carpenter, Matthew S. Waitkus, Catherine Y. Wang, Huishan Zhu, Landon J. Hansen, Lee H. Chen, et al. “Mutant IDH1 Disrupts the Mouse Subventricular Zone and Alters Brain Tumor Progression.” Mol Cancer Res 15, no. 5 (May 2017): 507–20. https://doi.org/10.1158/1541-7786.MCR-16-0485.Full Text Link to Item
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Song, Zhi-Jian, Zachary J. Reitman, Zeng-Yi Ma, Jian-Hua Chen, Qi-Lin Zhang, Xue-Fei Shou, Chuan-Xin Huang, et al. “The genome-wide mutational landscape of pituitary adenomas.” Cell Res 26, no. 11 (November 2016): 1255–59. https://doi.org/10.1038/cr.2016.114.Full Text Link to Item
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Chitneni, Satish K., Zachary J. Reitman, David M. Gooden, Hai Yan, and Michael R. Zalutsky. “Radiolabeled inhibitors as probes for imaging mutant IDH1 expression in gliomas: Synthesis and preliminary evaluation of labeled butyl-phenyl sulfonamide analogs.” Eur J Med Chem 119 (August 25, 2016): 218–30. https://doi.org/10.1016/j.ejmech.2016.04.066.Full Text Open Access Copy Link to Item
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Lu, Zheming, Jindong Sheng, Yujie Zhang, Jianhua Deng, Yong Li, Aiping Lu, Juan Zhang, et al. “Clonality analysis of multifocal papillary thyroid carcinoma by using genetic profiles.” J Pathol 239, no. 1 (May 2016): 72–83. https://doi.org/10.1002/path.4696.Full Text Link to Item
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Waitkus, Matthew S., Bill H. Diplas, and Hai Yan. “Isocitrate dehydrogenase mutations in gliomas.” Neuro Oncol 18, no. 1 (January 2016): 16–26. https://doi.org/10.1093/neuonc/nov136.Full Text Link to Item
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Huang, Dong-Sheng, Hou-Quan Tao, Xu-Jun He, Ming Long, Sheng Yu, Ying-Jie Xia, Zhang Wei, et al. “Prevalence of deleterious ATM germline mutations in gastric cancer patients.” Oncotarget 6, no. 38 (December 1, 2015): 40953–58. https://doi.org/10.18632/oncotarget.5944.Full Text Link to Item
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Feng, Jie, Shuyu Hao, Changcun Pan, Yu Wang, Zhen Wu, Junting Zhang, Hai Yan, Liwei Zhang, and Hong Wan. “The H3.3 K27M mutation results in a poorer prognosis in brainstem gliomas than thalamic gliomas in adults.” Hum Pathol 46, no. 11 (November 2015): 1626–32. https://doi.org/10.1016/j.humpath.2015.07.002.Full Text Link to Item
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Zhang, Zhen-Yu, Aden Ka-Yin Chan, Xiao-Jie Ding, Zhi-Yong Qin, Christopher S. Hong, Ling-Chao Chen, Xin Zhang, et al. “TERT promoter mutations contribute to IDH mutations in predicting differential responses to adjuvant therapies in WHO grade II and III diffuse gliomas.” Oncotarget 6, no. 28 (September 22, 2015): 24871–83. https://doi.org/10.18632/oncotarget.4549.Full Text Link to Item
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Gurzadyan, V. G., H. Yan, G. Vlahovic, A. Kashin, P. Killela, Z. Reitman, S. Sargsyan, G. Yegorian, G. Milledge, and B. Vlahovic. “Detecting somatic mutations in genomic sequences by means of Kolmogorov-Arnold analysis.” R Soc Open Sci 2, no. 8 (August 2015): 150143. https://doi.org/10.1098/rsos.150143.Full Text Link to Item
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Huang, Dong-Sheng, Zhaohui Wang, Xu-Jun He, Bill H. Diplas, Rui Yang, Patrick J. Killela, Qun Meng, et al. “Recurrent TERT promoter mutations identified in a large-scale study of multiple tumour types are associated with increased TERT expression and telomerase activation.” Eur J Cancer 51, no. 8 (May 2015): 969–76. https://doi.org/10.1016/j.ejca.2015.03.010.Full Text Link to Item
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Reitman, Zachary J., Sergey A. Sinenko, Eric P. Spana, and Hai Yan. “Genetic dissection of leukemia-associated IDH1 and IDH2 mutants and D-2-hydroxyglutarate in Drosophila.” Blood 125, no. 2 (January 8, 2015): 336–45. https://doi.org/10.1182/blood-2014-05-577940.Full Text Link to Item
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Reitman, Zachary J., Christopher G. Duncan, Ethan Poteet, Ali Winters, Liang-Jun Yan, David M. Gooden, Ivan Spasojevic, Laszlo G. Boros, Shao-Hua Yang, and Hai Yan. “Cancer-associated isocitrate dehydrogenase 1 (IDH1) R132H mutation and d-2-hydroxyglutarate stimulate glutamine metabolism under hypoxia.” J Biol Chem 289, no. 34 (August 22, 2014): 23318–28. https://doi.org/10.1074/jbc.M114.575183.Full Text Link to Item
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Archer, G. E., E. Reap, P. Norberg, X. Cui, R. Schmittling, J. Herndon, V. Chandramohan, et al. “Idh1 mutations as a immunotherapeutic target for brain tumors.” Neuro Oncol 16 Suppl 3 (July 2014): iii40. https://doi.org/10.1093/neuonc/nou208.65.Full Text Link to Item
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Yan, H., P. J. Killela, Z. J. Reitman, Y. Jiao, C. Bettegowda, N. Agrawal, L. A. Diaz, et al. “Tert promoter mutations occur frequently in gliomas and a subset of tumors derived from cells with low rates of self-renewal.” Neuro Oncol 16 Suppl 3 (July 2014): iii5–6. https://doi.org/10.1093/neuonc/nou206.18.Full Text Link to Item
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Jin, Genglin, Christopher J. Pirozzi, Lee H. Chen, Giselle Y. Lopez, Christopher G. Duncan, Jie Feng, Ivan Spasojevic, Darell D. Bigner, Yiping He, and Hai Yan. “Mutant IDH1 is required for IDH1 mutated tumor cell growth.” Oncotarget 3, no. 8 (August 2012): 774–82. https://doi.org/10.18632/oncotarget.577.Full Text Open Access Copy Link to Item
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Wortham, Matthew, Genglin Jin, Julia Lailai Sun, Darell D. Bigner, Yiping He, and Hai Yan. “Aberrant Otx2 expression enhances migration and induces ectopic proliferation of hindbrain neuronal progenitor cells.” Plos One 7, no. 4 (2012): e36211. https://doi.org/10.1371/journal.pone.0036211.Full Text Link to Item
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Duncan, Christopher G., and Hai Yan. “Genomic alterations and the pathogenesis of glioblastoma.” Cell Cycle 10, no. 8 (April 15, 2011): 1174–75. https://doi.org/10.4161/cc.10.8.15225.Full Text Link to Item
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Lopez, Giselle Y., Zachary J. Reitman, David Solomon, Todd Waldman, Darell D. Bigner, Roger E. McLendon, Steven A. Rosenberg, Yardena Samuels, and Hai Yan. “IDH1(R132) mutation identified in one human melanoma metastasis, but not correlated with metastases to the brain.” Biochem Biophys Res Commun 398, no. 3 (July 30, 2010): 585–87. https://doi.org/10.1016/j.bbrc.2010.06.125.Full Text Open Access Copy Link to Item
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Reitman, Zachary J., Natasha J. Olby, Christopher L. Mariani, Rachael Thomas, Matthew Breen, Darell D. Bigner, Roger E. McLendon, and Hai Yan. “IDH1 and IDH2 hotspot mutations are not found in canine glioma.” Int J Cancer 127, no. 1 (July 1, 2010): 245–46. https://doi.org/10.1002/ijc.25017.Full Text Link to Item
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Reitman, Zachary J., D Williams Parsons, and Hai Yan. “IDH1 and IDH2: not your typical oncogenes.” Cancer Cell 17, no. 3 (March 16, 2010): 215–16. https://doi.org/10.1016/j.ccr.2010.02.024.Full Text Link to Item
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Kanu, Okezie O., Betsy Hughes, Chunhui Di, Ningjing Lin, Jinrong Fu, Darell D. Bigner, Hai Yan, and Cory Adamson. “Glioblastoma Multiforme Oncogenomics and Signaling Pathways.” Clin Med Oncol 3 (April 8, 2009): 39–52. https://doi.org/10.4137/cmo.s1008.Full Text Link to Item
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Guruiangan, Sridharan, Hai Yan, Cory Adamson, Qun Shi, Roger McLendon, and Darell Bigner. “OTX2 IS ONCOGENIC AND PREDICTS DECREASED SURVIVAL IN MEDULLOBLASTOMA PATIENTS.” Neuro Oncology 11, no. 2 (April 1, 2009): 234–234.Link to Item
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Butz, James A., Hai Yan, Venugopal Mikkilineni, and Jeremy S. Edwards. “Detection of allelic variations of human gene expression by polymerase colonies.” Bmc Genet 5 (February 16, 2004): 3. https://doi.org/10.1186/1471-2156-5-3.Full Text Link to Item
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Davis, E., K. Krishnan, H. Yan, E. W. Newcomb, and J. J. Krolewski. “A mutant form of p135tyk2, an interferon-alpha inducible tyrosine kinase, suppresses the transformed phenotype of Daudi cells.” Leukemia 10, no. 3 (March 1996): 543–51.Link to Item
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Gupta, S., H. Yan, L. H. Wong, S. Ralph, J. Krolewski, and C. Schindler. “The SH2 domains of Stat1 and Stat2 mediate multiple interactions in the transduction of IFN-alpha signals.” Embo J 15, no. 5 (March 1, 1996): 1075–84.Link to Item
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Yan, H., K. Krishnan, A. C. Greenlund, S. Gupta, J. T. Lim, R. D. Schreiber, C. W. Schindler, and J. J. Krolewski. “Phosphorylated interferon-alpha receptor 1 subunit (IFNaR1) acts as a docking site for the latent form of the 113 kDa STAT2 protein.” Embo J 15, no. 5 (March 1, 1996): 1064–74.Link to Item
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Domanski, P., H. Yan, M. M. Witte, J. Krolewski, and O. R. Colamonici. “Homodimerization and intermolecular tyrosine phosphorylation of the Tyk-2 tyrosine kinase.” Febs Lett 374, no. 3 (November 6, 1995): 317–22. https://doi.org/10.1016/0014-5793(95)01094-u.Full Text Link to Item
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Yan, H., J. T. Lim, L. G. Contillo, and J. J. Krolewski. “Glutathione S-transferase fusion proteins mimic receptor dimerization in permeabilized cells.” Anal Biochem 231, no. 2 (November 1, 1995): 455–58. https://doi.org/10.1006/abio.1995.0080.Full Text Link to Item
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Greenlund, A. C., M. O. Morales, B. L. Viviano, H. Yan, J. Krolewski, and R. D. Schreiber. “Stat recruitment by tyrosine-phosphorylated cytokine receptors: an ordered reversible affinity-driven process.” Immunity 2, no. 6 (June 1995): 677–87. https://doi.org/10.1016/1074-7613(95)90012-8.Full Text Link to Item
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Colamonici, O., H. Yan, P. Domanski, R. Handa, D. Smalley, J. Mullersman, M. Witte, K. Krishnan, and J. Krolewski. “Direct binding to and tyrosine phosphorylation of the alpha subunit of the type I interferon receptor by p135tyk2 tyrosine kinase.” Mol Cell Biol 14, no. 12 (December 1994): 8133–42. https://doi.org/10.1128/mcb.14.12.8133-8142.1994.Full Text Link to Item
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Colamonici, O. R., H. Uyttendaele, P. Domanski, H. Yan, and J. J. Krolewski. “p135tyk2, an interferon-alpha-activated tyrosine kinase, is physically associated with an interferon-alpha receptor.” J Biol Chem 269, no. 5 (February 4, 1994): 3518–22.Link to Item
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Book Sections
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Pirozzi, C. J., A. B. Carpenter, T. Hennika, O. J. Becher, and H. Yan. “Tumor-Specific Mutations in Gliomas and their Implications for Immunotherapy.” In Translational Immunotherapy of Brain Tumors, 83–107, 2017. https://doi.org/10.1016/B978-0-12-802420-1.00005-3.Full Text
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hansen, L. H., B. Diplas, B. becher, and B. Yan. “Genetics of glioma.” In The Duke Glioma Handbook, translated by J. H. S. Sampson. Cambridge University Press, 2016.Link to Item
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López, G. Y., M. Samsky, R. Jones, C. Adamson, and H. Yan. “Genetic alterations in glioblastoma multiforme.” In Systems Biology of Cancer, 323–44, 2015. https://doi.org/10.1017/9780511979811.022.Full Text
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Adamson, D. C., and H. Yan. “Overview of oncogenesis.” In Garner and Klintworth’s Pathobiology of Ocular Disease Part B, Third Edition, 1163–74, 2007.
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Yan, H., and F. M. Giardiello. “Brain tumor–polyposis (BTP) syndrome.” In Russell and Rubinstein’s Pathology of Tumors of the Nervous System., 1003–10, 2006.
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Conference Papers
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Liu, Heng, Cheng Xu, Lee H. Chen, Bill H. Diplas, Jinjie Ling, Paula K. Greer, Martin Roskoski, et al. “Abstract 5821: The role of SMARCAL1 loss-of-function mutations in glioblastoma telomere maintenance.” In Cancer Research, 80:5821–5821. American Association for Cancer Research (AACR), 2020. https://doi.org/10.1158/1538-7445.am2020-5821.Full Text
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Peters, Katherine, Kendra Congdon, Gary Archer, Sarah Woodring, Denise Jaggers, Eric Lipp, Patrick Healy, et al. “SAFETY OF TUMOR-SPECIFIC PEPTIDE VACCINE TARGETING ISOCITRATE DEHYDROGENASE 1 MUTATION IN RECURRENT RESECTABLE LOW GRADE GLIOMA PATIENTS.” In Neuro Oncology, 21:vi8–vi8. OXFORD UNIV PRESS INC, 2019. https://doi.org/10.1093/neuonc/noz175.030.Full Text Link to Item
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Bowie, Michelle, Seethalakshmi Hariharan, Janell Hostettler, Kristen Roso, Yiping He, Christopher Pirozzi, Martin Roskoski, et al. “ATRX MUTATIONS PREDICT RESPONSE TO INNATE BASED THERAPY IN GLIOMA.” In Neuro Oncology, 21:126–126. OXFORD UNIV PRESS INC, 2019.Link to Item
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Gromeier, Matthias, Michael Brown, Nike Beuabier, Hai Yan, Yiping He, Gao Zhang, Annick Desjardins, et al. “TUMOR MUTATIONAL BURDEN PREDICTS RESPONSE TO ONCOLYTIC POLIO/RHINOVIRUS RECOMBINANT (PVSRIPO) IN MALIGNANT GLIOMA PATIENTS: ASSESSMENT OF TRANSCRIPTIONAL AND IMMUNOLOGICAL CORRELATES.” In Neuro Oncology, 21:7–7. OXFORD UNIV PRESS INC, 2019.Link to Item
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Diplas, Bill, Matthew Waitkus, Xujun He, Jackie Brosnan-Cashman, Heng Liu, Lee Chen, Zhaohui Wang, et al. “THE GENOMIC LANDSCAPE OF TRIPLE-NEGATIVE GLIOBLASTOMA.” In Neuro Oncology, 20:112–112. OXFORD UNIV PRESS INC, 2018.Link to Item
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Keir, Stephen, Matthew Waitkus, Martin Roskoski, Henry Friedman, Darell Bigner, Hai Yan, and David Ashley. “ESTABLISHMENT AND PRELIMINARY EVALUATION OF BEVACIZUMAB-RESISTANT GLIOMA XENOGRAFT MODELS.” In Neuro Oncology, 20:275–275. OXFORD UNIV PRESS INC, 2018.Link to Item
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Pirozzi, Christopher J., Catherine Y. Wang, Austin B. Carpenter, Huishan Zhu, Paula K. Greer, Roger E. McLendon, Darell D. Bigner, Yiping He, and Hai Yan. “Abstract 63: Driving brain tumorigenesis: Generation of a mutant IDH1 mouse model of progressive glioma.” In Cancer Research, 74:63–63. American Association for Cancer Research (AACR), 2014. https://doi.org/10.1158/1538-7445.am2014-63.Full Text
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Cheng, S., H. Feng, G. Y. Lopez, C. K. Kim, C. G. Duncan, A. Alvarez, R. Nishikawa, et al. “EGFR PHOSPHORYLATION OF DCBLD2 RECRUITS TRAF6 AND STIMULATES AKT-PROMOTED TUMORIGENESIS.” In Neuro Oncology, 16:iii16–17. Oxford University Press (OUP), 2014. https://doi.org/10.1093/neuonc/nou206.60.Full Text
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Chitneni, Satish, Zachary Reitman, Hai Yan, and Michael Zalutsky. “Radioiodinated AGI-5198 for in vivo imaging of isocitrate dehydrogenase 1 (IDH1) mutation in gliomas.” In Journal of Nuclear Medicine, Vol. 55. SOC NUCLEAR MEDICINE INC, 2014.Link to Item
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Guo, Changcun, Lee H. Chen, Yafen Huang, Chun-chi Chang, Ping Wang, Christopher J. Pirozzi, Xiaoxia Qin, et al. “MLL2 maintains neoplastic cell growth and global histone H3 lysine 4 monomethylation.” In Cancer Research, Vol. 74, 2014. https://doi.org/10.1158/1538-7445.AM2014-LB-82.Full Text Link to Item
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Reap, Elizabeth, Gerald Archer, Luis Sanchez-Perez, Pamela Norberg, Robert Schmittling, Smita Nair, Xiuyu Cui, et al. “TARGETING IDH1 MUTATIONS USING PEPTIDE VACCINES IN BRAIN TUMORS.” In Neuro Oncology, 15:71–71. OXFORD UNIV PRESS INC, 2013.Link to Item
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Killela, Patrick, Zachary Reitman, Yuchen Jiao, Roger McLendon, Bert Vogelstein, Darell Bigner, Luis Diaz, and Hai Yan. “Frequent ATRX, CIC, FUBP1 and IDH1 Mutations Refine the Classification of Malignant Gliomas.” In Journal of Neuropathology and Experimental Neurology, 72:542–542. LIPPINCOTT WILLIAMS & WILKINS, 2013.Link to Item
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Guo, Changcun, Chun-Chi Chang, Matthew Wortham, Lee Chen, Dawn Kernagis, Xiaoxia Qin, Young-wook Cho, et al. “GLOBAL IDENTIFICATION OF MLL2-TARGETED LOCI REVEALS MLL2'S ROLE IN DIVERSE SIGNALING PATHWAYS.” In Neuro Oncology, 15:9–9. OXFORD UNIV PRESS INC, 2013.Link to Item
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Keir, Stephen, Charles Pegram, Eric Lipp, Ahmed Rasheed, Vidyalakshmi Chandramohan, Chien-Tsun Kuan, Madan Kwatra, Hai Yan, and Darell Bigner. “ESTABLISHMENT OF SEVEN NEW PERMANENT PEDIATRIC BRAIN TUMOR LINES.” In Neuro Oncology, 15:10–10. OXFORD UNIV PRESS INC, 2013.Link to Item
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Wortham, Matthew, Zach Reitman, Yiping He, Darell Bigner, and Hai Yan. “ABERRANT Otx2 EXPRESSION ENHANCES MIGRATION AND INDUCES ECTOPIC PROLIFERATION OF HINDBRAIN NEURONAL PROGENITOR CELLS.” In Neuro Oncology, 15:2–2. OXFORD UNIV PRESS INC, 2013.Link to Item
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Wortham, Matthew, Genglin Jin, Julia Lailai Sun, Dare D. Bigner, and Hai Yan. “The medulloblastoma oncogene Otx2 enhances migration and permits ectopic proliferation of neuronal progenitor cells of the cerebellum and brainstem.” In Cancer Research, Vol. 72, 2012. https://doi.org/10.1158/1538-7445.AM2012-3352.Full Text Link to Item
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Parsons, Donald W., Hai Yan, Darell D. Bigner, Michael D. Taylor, Tom Curran, Mitchel S. Berger, and Victor E. Velculescu. “THE GENETIC LANDSCAPE OF MEDULLOBLASTOMA.” In Neuro Oncology, 13:I28–29. OXFORD UNIV PRESS INC, 2011.Link to Item
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Reitman, Zachary J., Genglin Jin, Edward D. Karoly, Ivan Spasojevic, Jian Yang, Kenneth W. Kinzler, Yiping He, Darell D. Bigner, Bert Vogelstein, and Hai Yan. “METABOLOMIC PROFILING OF A GLIOMA CELL LINE EXPRESSING IDH1 AND IDH2 MUTANTS.” In Neuro Oncology, 13:I22–23. OXFORD UNIV PRESS INC, 2011.Link to Item
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Wortham, Matthew, David C. Adamson, Qun Shi, Paul Northcott, Chunhui Di, Christopher Duncan, Jianjun Li, et al. “OTX2 IS A PREVALENT BUT TARGETABLE ONCOGENE IN Shh-INDEPENDENT MEDULLOBLASTOMAS.” In Neuro Oncology, 13:I30–I30. OXFORD UNIV PRESS INC, 2011.Link to Item
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Yan, Hai, Zachary J. Reitman, Genglin Jin, Ivan Spasojevic, Yiping He, Dare D. Bigner, Edward D. Karoly, Jian Yang, Kenneth W. Kinzler, and Bert Vogelstein. “Profiling the effects of IDH1 and IDH2 mutants on the glioma cell metabolome.” In Cancer Research, Vol. 71, 2011. https://doi.org/10.1158/1538-7445.AM2011-LB-257.Full Text Link to Item
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Duncan, Chris, Rebecca Leary, Jordan Cummins, Chunhui Di, Tian-Li Wang, Darell Bigner, Levy Kopelovich, Bert Vogelstein, Victor Velculescu, and Hai Yan. “IDENTIFICATION OF MICROBIAL DNAS IN BRAIN TUMORS.” In Neuro Oncology, 10:800–800. OXFORD UNIV PRESS INC, 2008.Link to Item
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Killela, Patrick, Chris Duncan, Roger Mclendon, Darell Bigner, and Hai Yan. “GENOMIC LANDSCAPE OF GLIOBLASTOMA.” In Neuro Oncology, 10:800–801. OXFORD UNIV PRESS INC, 2008.Link to Item
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Yan, Hai, Cory Adamson, Qun Shi, Chunhui Di, Chris Duncan, Roger Mclendon, and Darell Bigner. “The oncogenic role of OTX2 in medulloblastoma pathogenesis and its clinical implications as a tumor marker and therapeutic target.” In Neuro Oncology, 10:390–390. DUKE UNIV PRESS, 2008.Link to Item
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Yan, Hai, Qun Shi, Chunhui Di, Chris Duncan, and Darell Bigner. “Deregulation of an extraordinarily important developmental gene promotes medulloblastoma tumorigenesis.” In Neuro Oncology, 9:555–555. DUKE UNIV PRESS, 2007.Link to Item
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Adamson, D Cory, Chunhui Di, Qun Shi, Roger E. McLendon, Darell D. Bigner, and Hai Yan. “Prognostic significance of OTX2 in medulloblastoma.” In Cancer Research, Vol. 66. AMER ASSOC CANCER RESEARCH, 2006.Link to Item
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Shi, Qun, Chunhui Di, Chris Duncan, David C. Adamson, Roger McLendon, Darell D. Bigner, and Hai Yan. “Molecular characterization of the role of OTX2 in medulloblastoma pathogenesis.” In Cancer Research, Vol. 66. AMER ASSOC CANCER RESEARCH, 2006.Link to Item
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