Hai Yan

Overview:

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.

Positions:

Henry S. Friedman Distinguished Professor of Neuro-Oncology in the School of Medicine

Pathology
School of Medicine

Professor of Pathology

Pathology
School of Medicine

Professor of Pharmacology and Cancer Biology

Pharmacology & Cancer Biology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 1991

Beijing Medical University (China)

Ph.D. 1997

Columbia University

Research Associate, Howard Hughes Institute

Johns Hopkins University

Publications:

Brain tumor–polyposis (BTP) syndrome

© 2006 Roger E. McLendon, Marc K. Rosenblum, and Darell D. Bigner. All rights reserved. Brain tumor–polyposis (BTP) syndrome is a rare genetic disease characterized clinically by the concurrence of multiple colorectal adenomas and primary brain tumors. The BTP syndromes can be subdivided into two major categories based upon clinical phenotype, modes of inheritance and underlying gene mutations. Type I BTP syndrome (Turcot's syndrome) is characterized by the presence of malignant gliomas and multiple benign colorectal adenomas in the second or third decade. The frequent presence of consanguinity and the absence of parental disease indicate that Type I BTP syndrome is inherited in an autosomal recessive manner. The genes responsible for Type I BTP syndrome include the mismatch repair (MMR) genes, which are also linked to hereditary nonpolyposis colorectal cancer (HNPCC, or Lynch syndrome). The original BTP case described by Turcot fits into this category. In contrast, a second, Type II BTP syndrome (Crail's syndrome) typically presents with a medulloblastoma instead of astrocytic tumors, and the number and size of colonic polyps is similar to those in familial adenomatous polyposis (FAP). In this syndrome, colorectal polyposis usually occurs in multiple generations and evidence for consanguinity is lacking, indicative of an autosomal dominant mode of inheritance. Adenomatous polyposis coli (APC) tumor suppressor gene germ-line mutations have been found in most cases of Type II BTP syndrome patients. Also, FAP patients have a significant increase in the relative risk of developing a medulloblastoma compared to the general population. Therefore, Type II BTP syndrome may represent a manifestation of the APC gene defect in FAP families, as first described by Crail. Interestingly, APC somatic mutations are found in most sporadic colorectal adenomas as well as in a smaller fraction of sporadic medulloblastomas without associated FAP or BTP syndromes. Further illustration of the molecular mechanism of tumorigenesis, both of colorectal and primary brain tumors in BTP syndrome, will provide useful diagnostic and prognostic information and will elucidate important mechanisms in the more common sporadic forms of brain and colon tumors.
Authors
Yan, H; Giardiello, FM
MLA Citation
Yan, H., and F. M. Giardiello. “Brain tumor–polyposis (BTP) syndrome.” Russell and Rubinstein’s Pathology of Tumors of the Nervous System., 2006, pp. 1003–10.
URI
https://scholars.duke.edu/individual/pub1431947
Source
scopus
Published Date
Start Page
1003
End Page
1010

The integrated genomic and epigenomic landscape of brainstem glioma.

Brainstem gliomas are a heterogeneous group of tumors that encompass both benign tumors cured with surgical resection and highly lethal cancers with no efficacious therapies. We perform a comprehensive study incorporating epigenetic and genomic analyses on a large cohort of brainstem gliomas, including Diffuse Intrinsic Pontine Gliomas. Here we report, from DNA methylation data, distinct clusters termed H3-Pons, H3-Medulla, IDH, and PA-like, each associated with unique genomic and clinical profiles. The majority of tumors within H3-Pons and-H3-Medulla harbors H3F3A mutations but shows distinct methylation patterns that correlate with anatomical localization within the pons or medulla, respectively. Clinical data show significantly different overall survival between these clusters, and pathway analysis demonstrates different oncogenic mechanisms in these samples. Our findings indicate that the integration of genetic and epigenetic data can facilitate better understanding of brainstem gliomagenesis and classification, and guide future studies for the development of novel treatments for this disease.
Authors
Chen, LH; Pan, C; Diplas, BH; Xu, C; Hansen, LJ; Wu, Y; Chen, X; Geng, Y; Sun, T; Sun, Y; Zhang, P; Wu, Z; Zhang, J; Li, D; Zhang, Y; Wu, W; Wang, Y; Li, G; Yang, J; Wang, X; Xu, C; Wang, S; Waitkus, MS; He, Y; McLendon, RE; Ashley, DM; Yan, H; Zhang, L
MLA Citation
Chen, Lee H., et al. “The integrated genomic and epigenomic landscape of brainstem glioma.Nat Commun, vol. 11, no. 1, June 2020, p. 3077. Pubmed, doi:10.1038/s41467-020-16682-y.
URI
https://scholars.duke.edu/individual/pub1447966
PMID
32555164
Source
pubmed
Published In
Nature Communications
Volume
11
Published Date
Start Page
3077
DOI
10.1038/s41467-020-16682-y

SAFETY OF TUMOR-SPECIFIC PEPTIDE VACCINE TARGETING ISOCITRATE DEHYDROGENASE 1 MUTATION IN RECURRENT RESECTABLE LOW GRADE GLIOMA PATIENTS

Authors
Peters, K; Congdon, K; Archer, G; Woodring, S; Jaggers, D; Lipp, E; Healy, P; Herndon, J; Soher, B; Vlahovic, G; Johnson, M; Randazzo, D; Desjardins, A; Friedman, H; Friedman, A; Ashley, D; Yan, H; Sampson, J
MLA Citation
Peters, Katherine, et al. “SAFETY OF TUMOR-SPECIFIC PEPTIDE VACCINE TARGETING ISOCITRATE DEHYDROGENASE 1 MUTATION IN RECURRENT RESECTABLE LOW GRADE GLIOMA PATIENTS.” Neuro Oncology, vol. 21, OXFORD UNIV PRESS INC, 2019, pp. 8–8.
URI
https://scholars.duke.edu/individual/pub1432783
Source
wos
Published In
Neuro Oncology
Volume
21
Published Date
Start Page
8
End Page
8

TUMOR MUTATIONAL BURDEN PREDICTS RESPONSE TO ONCOLYTIC POLIO/RHINOVIRUS RECOMBINANT (PVSRIPO) IN MALIGNANT GLIOMA PATIENTS: ASSESSMENT OF TRANSCRIPTIONAL AND IMMUNOLOGICAL CORRELATES

Authors
Gromeier, M; Brown, M; Beuabier, N; Yan, H; He, Y; Zhang, G; Desjardins, A; Herndon, J; Bolognesi, D; Friedman, A; Friedman, H; McSherry, F; Lin, X; Wei, Z; Nair, S; Peters, K; Randazzo, D; Sampson, J; McLendon, R; Bigner, D; Ashley, D
URI
https://scholars.duke.edu/individual/pub1433193
Source
wos
Published In
Neuro Oncology
Volume
21
Published Date
Start Page
7
End Page
7

Overview of oncogenesis

© 2008 by Informa Healthcare USA, Inc. The beginning of this century brought with it an explosion of knowledge in the field of oncogenesis. Perhaps the most prominent aspect of our collective knowledge of carcinogenesis is its heterogeneous nature in every respect, from the gene mutating events that initiate the process to the histological and clinical presentations. Instead of isolated specific carcinogenic culprits, cancer-related research has uncovered a plethora of different contributing factors leading to its pathogenesis. The explosion of studies in this field has taught us that this is a disease with multiple causes, which will likely require a similar multitude of therapeutic approaches.
Authors
MLA Citation
Adamson, D. C., and H. Yan. “Overview of oncogenesis.” Garner and Klintworth’s Pathobiology of Ocular Disease Part B, Third Edition, 2007, pp. 1163–74.
URI
https://scholars.duke.edu/individual/pub1431945
Source
scopus
Published Date
Start Page
1163
End Page
1174

Research Areas:

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
CD4 Antigens
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
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