Erwin G. Van Meir, PhD

 Erwin Van Meir

Erwin G. Van Meir, PhD
Professor, Departments of Neurosurgery and Hematology & Medical Oncology
Leader, Winship Cancer Institute Cancer Cell Biology Program
Founding Director, Graduate Program in Cancer Biology
Director, Laboratory for Molecular Neuro-Oncology
Emory University School of Medicine
1365C Clifton Rd. NE
Atlanta GA 30322

Dr. Van Meir, PhD directs the Laboratory of Molecular Neuro-Oncology and participates in a multidisciplinary neuro-oncology team that designs new approaches for brain tumor therapy. He is the Founding Director of the Laney Graduate School's Cancer Biology Graduate Program and the Leader of the Cancer Cell Biology program at the Winship Cancer Institute. Dr. Van Meir has extensive experience in cancer research. He was trained in molecular biology at the Universities of Fribourg and Lausanne, Switzerland where he obtained his PhD in 1989. Dr. Van Meir pursued postdoctoral work at the Ludwig Institute for Cancer Research in San Diego, and joined the Faculty of Emory University in 1998.

Dr. Van Meir and his colleagues have made many original contributions to cancer research. His team's research interest over the last 20 years has been in translational cancer research, with a major focus on neuro-oncology (gliomas and medulloblastomas) and more recently Ewing sarcoma and uveal melanoma. They strive to understand the molecular basis for human tumor development and how we can use this knowledge to devise new diagnostics and therapeutics that will improve patient survival. In studying how genetic alterations can affect brain cancer biology, they found that the p53 tumor suppressor pathway can control anti-angiogenic responses (see Van Meir et al, Nature Genetics, 1994; Zerrouqi et al, J. Clinical Investigation, 2012). They have taken a particular interest in Brain Angiogenesis Inhibitor-1 (BAI1), a GPCR-like molecule as a tumor suppressor and regulator of synaptogenesis in the brain. They showed that BAI1 expression is absent in a majority of gliomas due to epigenetic silencing (Zhu et al, Cancer Research, 2011) and that its N-terminus is cleaved to release 120 and 40 kDa fragments they named vasculostatins (Kaur et al, Oncogene, 2005; Cork et al, Oncogene, 2012). Vasculostatins are potent inhibitors of angiogenesis and can inhibit brain tumor growth (Kaur et al, Cancer Research, 2009). To better understand the physiological role of BAI1 in the brain they have generated a line of BAI1 knockout/LacZ knockin mice. They are using these mice to study roles for BAI1 in normal central nervous system development and brain tumor formation. They also develop novel therapeutic approaches for cancer using oncolytic adenoviruses and anti-angiogenic molecules including small molecule inhibitors of the hypoxia-inducible factor pathway (Tan et al, Cancer Research, 2005; Narita et al, Clinical Cancer Research, 2009; Tan et al, Biorg Med Chem Letters, 2011). They have further interest in identifying new biomarkers for neuro-oncology, using proteomic and metabolomic analyses of the cerebrospinal fluid (Khwaja et al, J. Proteomics Research, 2007; Kalinina et al, J. Molecular Medicine, 2012). They aim to translate these novel biomarkers and therapeutic agents to testing in clinical trials with the hope to improve cancer patient treatment. The principal modeling systems they use are glioblastoma, medulloblastoma, and Ewing sarcoma, all highly malignant cancers, although the experimental therapeutics they develop are applicable to the cure of many solid malignancies.

Dr. Van Meir's research, supported by the NIH and many private foundations, is described in more than 150 peer-reviewed international scientific publications that have cumulated over 10,000 citations. He is also the author of several US and foreign patents. His contributions have been presented in over 160 invited seminars worldwide and have furthered the understanding of brain tumor biology and genetics, as well as led to the development novel preclinical therapeutic approaches for cancer. He serves as a reviewer for over 30 international cancer research journals, is a current member of the editorial board of Frontiers in Bioscience and the International Journal of Oncology, and is a former editor of several other cancer journals. He has trained multiple undergraduate and graduate students, medical fellows and postdocs and is a member of the Graduate Division of Biological and Biochemical Sciences at Emory, where he participates in the programs in Cancer Biology, Genetics and Molecular Biology and Neurosciences. Dr. Van Meir is active in several scientific societies and foundations, including the Society for Neuro-Oncology and the Southeastern Brain Tumor Foundation.

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Refereed Publications (last 5 years)

Click here to see Dr. Van Meir's Google Scholar profile with all publications.

Klenotic PA, et al (2010) Histidine-rich glycoprotein modulates the anti-angiogenic effects of Vasculostatin. Am J Pathol 176, 2039-50

Iskow RC, et al (2010) Natural mutagenesis of human genomes by endogenous retrotransposons Cell 141, 1253-1261

Cooper LAD, et al (2010) An integrative approach for in silico glioma research IEEE Trans BioMed Eng 57, 2617-21

Tan C, et al (2011) Sulfonamides as a New Scaffold for Hypoxia Inducible Factor Pathway Inhibitors. Bioorg Med Chem Lett 21, 5528-32

Zhu D, Hunter S, Vertino PM, and Van Meir EG (2011) Overexpression of MBD2 in Glioblastoma Maintains Epigenetic Silencing and Inhibits the Anti-Angiogenic Function of the Tumor Suppressor Gene BAI1. Cancer Research 71, 5859-70

Kong J, et al (2011) Integrative, Multi-modal Analysis of Glioblastoma Using TCGA Molecular Data, Pathology Images and Clinical Outcomes. IEEE Trans BioMed Eng 58, 3469-74

Reid-Mooring S, et al (2011) Design and synthesis of novel small molecule inhibitors of the Hypoxia Inducible Factor Pathway. J Med Chem 54, 8471-89

Zerrouqi A, et al (2012) P14ARF inhibits human glioblastoma-induced angiogenesis by upregulating the expression of TIMP3. J Clin Invest 122, 1283-95

Cooper LAD, et al (2012) The tumor microenvironment strongly impacts master transcriptional regulators and gene expression class of glioblastoma. Am J Pathology 180, 2108-19

Mun J, et al (2012) Structure-activity relationship of 2,2-dimethyl-2H-chromene based arylsulfonamide analogs of 3,4-dimethoxy-N-[(2,2-dimethyl-2H-chromen-6-yl)methyl]-N-phenylbenzenesulfonamide, a novel small molecule Hypoxia Inducible Factor-1 (HIF-1) pathway inhibitor and anti-cancer agent. Bioorg Med Chemistry 20, 4590-97

Northcott PA, et al (2012) Subgroup specific structural variation across 1,000 medulloblastoma genomes. Nature 488, 49-56

Mun J, et al (2012) Design and in vitro activities of N-alkyl-N-[(8-R-2,2-dimethyl-2H-chromen-6-yl)methyl] heteroarylsulfonamides, novel small molecule Hypoxia Inducible Factor-1 (HIF-1) pathway inhibitors and anti-cancer agents. J Med Chemistry 55, 6738-50

Shi Q, et al (2012) Binding Model for the Interaction of Anti-cancer Arylsulfonamides with the p300 Transcription co-factor. ACS Med Chem Letters 3, 620-5

Kalinina J, et al (2012) Detection of "Oncometabolite" 2-Hydroxyglutarate by Magnetic Resonance Analysis as a Biomarker of IDH1/2 Mutations in Glioma. J Mol Medicine 90, 1161-71

Wang W, et al (2012) KCN1, a novel synthetic sulfonamide anticancer agent: In vitro and in vivo anti-pancreatic cancer activities and preclinical pharmacology. PLoS ONE 7: e44883

Cork S, et al (2012) A proprotein convertase/MMP-14 proteolytic cascade releases a novel 40 kDa vasculostatin from tumor suppressor BAI1. Oncogene 31, 5144-52 PMID: 22330140

Yin S, et al (2012) Arylsulfonamide KCN1 inhibits in vivo glioma growth and blocks HIF signaling by disrupting HIF-1α interaction with co-factors p300/CBP. Clinical Cancer Res 18, 6623-33

Shao J, et al (2013) Design, synthesis and evaluation of the cytotoxicity of a N-mustard and paclitaxel conjugate prodrug. J Chin Pharm Sciences 22: 137-143

Zhukova N, et al (2013) Subgroup Specific Prognostic Implications of TP53 Mutation in Medulloblastoma. J Clinical Oncology 31, 2927-35

Stephenson JR, et al (2013) Brain-Specific Angiogenesis Inhibitor-1 Signaling, Regulation and Enrichment in the Postsynaptic Density. J Biological Chemistry 288, 22248-56

Brennan C, et al (2013) The Somatic Genomic Landscape of Glioblastoma. Cell 155, 462-477

Akers JC, et al (2013) miR-21 in the Extracellular Vesicles (EVs) of Cerebrospinal Fluid (CSF): a Platform for Glioblastoma Biomarker Development. PloS ONE 8:e78115

Remke M, et al (2013) TERT promoter mutations are highly recurrent in SHH subgroup medulloblastoma. Acta Neuropathologica 126, 917-29

Shih DJH et al (2013) Cytogenetic Prognostication within Medulloblastoma Subgroups. J Clinical Oncology (in press)

Fan J, et al (2013) Tyr-phosphorylation of PDP1 toggles recruitment between ACAT1 and SIRT3 to regulate pyruvate dehydrogenase complex. Molecular Cell (in press)

Zerrouqi A, et al (2013) p14ARF suppresses tumor-induced thrombosis by regulating the tissue factor pathway. Cancer Research (in revision)

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Review Articles (last 10 years)

Post D.E, et al (2004) Replicative oncolytic herpes simplex viruses in combination cancer therapies. Curr Gene Ther 4, 41-51

Brat DJ and Van Meir EG (2004) Vaso-occlusive and pro-thrombotic mechanisms associated with tumor hypoxia, necrosis and accelerated growth in glioblastoma. Lab Invest 84, 397-405

Bellail A, et al (2004) Microregional extracellular matrix heterogeneity in brain modulates glioma cell invasion. Int J Biochem & Cell Biol 36, 1046-69

Van Meir EG, et al (2004) Emerging molecular therapies for brain tumors. Semin Oncol 31, 38-46

Chu RL, et al (2004). Use of replicative oncolytic adenoviruses in combination therapy for cancer. Clin Cancer Res 10, 5299-5312

Kaur B, et al (2004) Genetic and hypoxic regulation of angiogenesis in gliomas. J Neuro-Oncol 70, 229-243

Kaur B, et al (2005) Hypoxia and the hypoxia-inducible-factor pathway in glioma growth and angiogenesis. Neuro-Oncol 7, 134-153

Brat DJ, et al (2005) The role of Interleukin-8 and its receptors in gliomagenesis and tumoral angiogenesis. Neuro-Oncol 7, 122-133

Post DE, et al (2005) Cancer Scene Investigation: how a cold virus became a cancer killer. Future Oncology 1, 247-258

Belozerov V and Van Meir EG (2005) Hypoxia Inducible factor-1: a novel target for cancer therapy. Anti-Cancer Drugs 16, 901-909

Rong Y, et al (2006) “Pseudopalisading” necrosis in glioblastoma: a familiar morphologic feature that links vascular pathology, hypoxia and angiogenesis. J Neuropathol Exp Neurol 65, 529-539

Belozerov V and Van Meir EG (2006) Inhibitors of Hypoxia Inducible Factor-1 signaling. Current Opinion in Investigational Drugs 7, 1067-1076

Hadjipanayis CG and Van Meir EG (2009) Tumor initiating cells in malignant gliomas: biology and implications for therapy. J Mol Medicine 87, 363-374

Hadjipanayis CG and Van Meir EG (2009) Brain cancer propagating cells: biology, genetics, and targeted therapies. Trends Mol Medicine 15, 519-30

Van Meir EG, Hadjipanayis CG, Norden AD, Shu HK, Wen PY and Olson JJ (2010) Exciting new advances in neuro-oncology: the avenue to a cure for malignant glioma. CA Cancer J Clin 60, 166-193

Cork S, and Van Meir EG (2011) Emerging roles for the BAI1 protein family in phagocytosis, synaptogenesis, neurovasculature and tumor development. J Mol Medicine 89, 743-752

Kalinina J, et al (2011) Proteomics of gliomas: initial biomarker discovery and evolution of technology. Neuro-Oncology 13, 926-42

Nduom, EKE, et al (2012) Glioblastoma cancer stem-like cells: Implications for Pathogenesis and Treatment. The Cancer Journal 18, 100-1067

Burroughs, S, et al (2013) Hypoxia Inducible Factor pathway inhibitors as anti-cancer therapeuticsFuture Medicinal Chemistry 5, 553-72


Books

CHAPTERS:

Rosenblum MK, Matsutani M, and Van Meir EG (2000). Central nervous system germ cell tumors. In Tumors of the Nervous System. Kleihues, P. and Cavenee, W.K. (eds.), World Health Organization Classification of Tumors, International Agency for Research on Cancer, Lyon p.207-214

Cavenee WK, Burger PC and Van Meir EG (2000). Turcot syndrome. In Tumors of the Nervous System. Kleihues, P. and Cavenee, W.K. (eds.), World Health Organization Classification of Tumors, International Agency for Research on Cancer, Lyon p.238-239

Van Meir EG, Hao C, Post DE, Liau L and Brat DJ (2003). Therapeutic targeting of molecular pathways that induce brain tumor development. In Genomic and Molecular Neuro-Oncology. Zhang W. and Fuller GN (eds.) Jones and Bartlett Publishers Inc. p.303-331

Dey, N, Durden DL and Van Meir EG (2006) Cytokine expression and signaling in CNS tumors. In Cytokines and the CNS II. Benveniste EN and Ransohoff RM (eds) CRC Press. p.193-242.

Cavenee WK, Burger PC, Leung SY and Van Meir EG (2007) Turcot syndrome. In WHO Classification of Tumors of the Central Nervous System. Louis D, Ohgaki H, Wiestler O and Cavenee, W.K. (eds.), International Agency for Research on Cancer, Lyon p.229-231

Khwaja FW and Van Meir EG (2009) Past, present and future of proteomics for CNS tumors In CNS cancer: Models, Prognostic Factors and Targets, Van Meir EG (ed.) Humana Press, Springer

Post DE and Van Meir EG (2009) The development of targeted cancer therapy adenoviruses for malignant glioma treatment In CNS cancer: Models, Prognostic Factors and Targets, Van Meir EG (ed.) Humana Press, Springer

Yin S and Van Meir EG (2009) The p53 pathway in CNS tumors In CNS cancer: Models, Prognostic Factors and Targets, Van Meir EG (ed.) Humana Press, Springer

BOOK REVIEWS:

Van Meir EG (1997) Cytokines and the CNS (book review) Chem Neuroanat 13, 141-144.

BOOK EDITOR:

CNS Cancer: Models, Prognostic Factors and Targets., Erwin G Van Meir, Editor Humana Press (Springer) In Progress-2009 print date. Cancer Drug Discovery and Development series, Dr. Beverly Teicher, series Editor

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