Vanderbilt University School of
El-Rifai, Wael , M.D., Ph.D.
Professor of Surgery
Professor of Cancer Biology
H. William Scott, Jr., Chair in Surgery
Phone Number: 615-322 7934
1255 Light Hall
2215 Garland Avenue 1255 Light Hall 37232-2733
Cancer genetics, molecular genetics, cancer biology, epigenetics, gastric cancer, gastroesophageal cancer, Barrett's, drug resistrance, molecular targets, therapeutic targets,Apoptosis,Cancer,Cell cycle,Gene regulation,Genetics,Genome,Genomics,Human Genetics,Malignancy,Molecular medicine,Mutation,Proteomics,Signal transduction,Transcription,Transcription factor
Cancer Genetics, Molecular Biology, upper gastrointestinal cancer, Barrett's adenocarcinoma, gastric cancer
Wael El-Rifai, MD., Ph.D.
Professor, Surgery & Cancer Biology
Director, Surgical Oncology Research
Dr. El-Rifai has a long-standing interest in understanding the modulation of molecular pathways through genetic and epigenetic events. His research is focused on upper gastrointestinal carcinomas (UGCs) with two main goals:
1. Translational OncoGenomics in upper gastrointestinal carcinomas
The El-Rifai laboratory has extensive expertise in the dissection of genetic and epigenetic alterations in upper gastrointestinal carcinomas (UGC). This group of tumors includes distal gastric tumors and proximal adenocarcinomas of the gastroesophageal junctional (GEJ) and lower esophagus. Proximal adenocarcinomas are the fastest rising tumors in the United States as well as in the rest of the western world. In my laboratory, we apply comprehensive, molecular-analysis-approaches with the integration of data in order to understand the molecular anatomy of these tumors. Several high-throughput technologies are utilized in his research. These include comparative genomic hybridization, microarrays, serial analysis of gene expression, and proteomic approaches. The El-Rifai laboratory identified a number of genomic hot spots and has systematically characterized the 1q, 17q, and 20q amplicons by combining the genomic data with gene expression data. At 17q21 he identified and characterized a 168 kb critical amplicon region that contains several known oncogenes side-by-side such as ERBB2, GRB7, and TOP2A. We have collected more than 400 tumors on tissue microarrays. These TMAs are continuously analyzed for identification of the clinical and histopathological significance of molecular alterations. Dr. El-Rifai?s lab was the first group of investigators to reveal Darpp-32 and its isoforms as novel cancer genes.
Our research extends to encompass animal models as tools of identification of tumor development and progression. In this direction, we have obtained TFF1 knockout mice that develop premalignant gastric dysplasia. Dr. El-Rifai laboratory has characterized this model and used it to identify alterations in molecular pathways that occur in a premalignant state. Using this approach, his research group discovered a number of previously unknown genes in gastric tumorigenesis and was able to validate the findings in human premalignant conditions. These genes include GPx3, Claudin-7, and Caveolin.
Dr. El-Rifai has demonstrated DNA promoter hypermethylation as a mechanism of down-regulation and loss of expression of several novel genes such as MT3, MGMT, DAPK, and GPX3. He has further shown that some of these changes are early events initiated in premalignant states such as in Barrett?s dysplasia. Recently, we have added to our laboratory the cutting-edge, pyrosequencing technology (Biotage) for a high through-put, robust, quantitative analysis of promoter CpG methylation sites.
2. Cellular effects and signaling transduction in UGCs
In line with his translational research component, Dr. El-Rifai laboratory is primarily interested in identifying anti-apoptotic/pro-survival targets that contribute to drug resistance. At this time, the work is focused in understanding the p53-dependent and independent mechanisms that contribute to this phenotype. Our work has demonstrated that Darpp-32 is a potent antiapoptotic gene that provides a phenotype that is drug resistant to cancer cells against several chemotherapeutic agents. This drug resistant phenotype was through a p53-independent mechanism that included up-regulation and activation of mitochondrial Bcl2 prosurvival proteins. In my laboratory, we use normal and transformed cells, specific antibodies and purified protein kinases to show phosphorylation controls activity. We continue to establish the oncogenic properties and downstream targets of Darpp-32 and/or t-Darpp in order to understand the signaling pathways that are regulated by Darpp-32 in cancer. In addition to studies on Darpp-32, our lab has identified COBRA1 as a novel gene that regulates the transcription of TFF1 expression in UGCs. Our work continues to focus on investigating the oncogenic properties of both DARPP-32 and COBRA1 in these tumors.
For a list of El-Rifai lab publications:
Sehdev, V, Katsha, A, Arras, J, Peng, D, Soutto, M, Ecsedy, J, Zaika, A, Belkhiri, A, El-Rifai, W. HDM2 Regulation by AURKA Promotes Cell Survival in Gastric Cancer. Clin Cancer Res, 20(1), 76-86, 2014.
Belkhiri, A, El-Rifai, W. 5-Methylcytosine hydroxylation-mediated LINE-1 hypomethylation: a novel mechanism of proto-oncogenes activation in colorectal cancer. Gut, , , 2013.
Chen, Z, Saad, R, Jia, P, Peng, D, Zhu, S, Washington, MK, Zhao, Z, Xu, Z, El-Rifai, W. Gastric adenocarcinoma has a unique microRNA signature not present in esophageal adenocarcinoma. Cancer, 119(11), 1985-93, 2013.
Cleveland, SM, Smith, S, Tripathi, R, Mathias, EM, Goodings, C, Elliott, N, Peng, D, El-Rifai, W, Yi, D, Chen, X, Li, L, Mullighan, C, Downing, JR, Love, P, Dav??, UP. Lmo2 induces hematopoietic stem cell-like features in T-cell progenitor cells prior to leukemia. Stem Cells, 31(5), 882-94, 2013.
Erdogan, B, Bosompem, A, Peng, D, Han, L, Smith, E, Kennedy, ME, Alford, CE, Wu, H, Zhao, Z, Mosse, CA, El-Rifai, W, Kim, AS. Methylation of promoters of microRNAs and their host genes in myelodysplastic syndromes. Leuk Lymphoma, 54(12), 2720-7, 2013.
Katsha, A, Soutto, M, Sehdev, V, Peng, D, Washington, MK, Piazuelo, MB, Tantawy, MN, Manning, HC, Lu, P, Shyr, Y, Ecsedy, J, Belkhiri, A, El-Rifai, W. Aurora kinase A promotes inflammation and tumorigenesis in mice and human gastric neoplasia. Gastroenterology, 145(6), 1312-22.e1-8, 2013.
Lim, J, Duong, T, Do, N, Do, P, Kim, J, Kim, H, El-Rifai, W, Ruley, HE, Jo, D. Antitumor activity of cell-permeable RUNX3 protein in gastric cancer cells. Clin Cancer Res, 19(3), 680-90, 2013.
Lim, J, Duong, T, Lee, G, Seong, BL, El-Rifai, W, Ruley, HE, Jo, D. The effect of intracellular protein delivery on the anti-tumor activity of recombinant human endostatin. Biomaterials, 34(26), 6261-71, 2013.
O''Neal, RL, Nam, KT, LaFleur, BJ, Barlow, B, Nozaki, K, Lee, HJ, Kim, WH, Yang, HK, Shi, C, Maitra, A, Montgomery, E, Washington, MK, El Rifai, W, Drapkin, RI, Goldenring, JR. Human epididymis protein 4 is up-regulated in gastric and pancreatic adenocarcinomas. Hum Pathol, 44(5), 734-42, 2013.
Peng, D, Hu, T, Soutto, M, Belkhiri, A, Zaika, A, El-Rifai, W. Glutathione peroxidase 7 has potential tumour suppressor functions that are silenced by location-specific methylation in oesophageal adenocarcinoma. Gut, , , 2013.
Saad, R, Chen, Z, Zhu, S, Jia, P, Zhao, Z, Washington, MK, Belkhiri, A, El-Rifai, W. Deciphering the unique microRNA signature in human esophageal adenocarcinoma. PLoS One, 8(5), e64463, 2013.
Schneider, BG, Piazuelo, MB, Sicinschi, LA, Mera, R, Peng, DF, Roa, JC, Romero-Gallo, J, Delgado, AG, de Sablet, T, Bravo, LE, Wilson, KT, El-Rifai, W, Peek, RM, Correa, P. Virulence of infecting Helicobacter pylori strains and intensity of mononuclear cell infiltration are associated with levels of DNA hypermethylation in gastric mucosae. Epigenetics, 8(11), 1153-61, 2013.
Sehdev, V, Katsha, A, Ecsedy, J, Zaika, A, Belkhiri, A, El-Rifai, W. The combination of alisertib, an investigational Aurora kinase A inhibitor, and docetaxel promotes cell death and reduces tumor growth in preclinical cell models of upper gastrointestinal adenocarcinomas. Cancer, 119(4), 904-14, 2013.
Zaika, E, Bhardwaj, V, Wei, J, Washington, MK, Souza, R, El-Rifai, W, Zaika, A. Proinflammatory cytokines and bile acids upregulate ??Np73 protein, an inhibitor of p53 and p73 tumor suppressors. PLoS One, 8(5), e64306, 2013.
Zhu, S, Hong, J, Tripathi, MK, Sehdev, V, Belkhiri, A, El-Rifai, W. Regulation of CXCR4-mediated invasion by DARPP-32 in gastric cancer cells. Mol Cancer Res, 11(1), 86-94, 2013.
Feng, J, Pan, X, Yu, J, Chen, Z, Xu, H, El-Rifai, W, Zhang, G, Xu, Z. Functional PstI/RsaI polymorphism in CYP2E1 is associated with the development, progression and poor outcome of gastric cancer. PLoS One, 7(9), e44478, 2012.
Hong, J, Katsha, A, Lu, P, Shyr, Y, Belkhiri, A, El-Rifai, W. Regulation of ERBB2 receptor by t-DARPP mediates trastuzumab resistance in human esophageal adenocarcinoma. Cancer Res, 72(17), 4504-14, 2012.
Peng, DF, Hu, TL, Schneider, BG, Chen, Z, Xu, ZK, El-Rifai, W. Silencing of glutathione peroxidase 3 through DNA hypermethylation is associated with lymph node metastasis in gastric carcinomas. PLoS One, 7(10), e46214, 2012.
Rau, TT, Rogler, A, Frischauf, M, Jung, A, Konturek, PC, Dimmler, A, Faller, G, Sehnert, B, El-Rifai, W, Hartmann, A, Voll, RE, Schneider-Stock, R. Methylation-dependent activation of CDX1 through NF-??B: a link from inflammation to intestinal metaplasia in the human stomach. Am J Pathol, 181(2), 487-98, 2012.
Wei, J, Noto, J, Zaika, E, Romero-Gallo, J, Correa, P, El-Rifai, W, Peek, RM, Zaika, A. Pathogenic bacterium Helicobacter pylori alters the expression profile of p53 protein isoforms and p53 response to cellular stresses. Proc Natl Acad Sci U S A, 109(38), E2543-50, 2012.
Belkhiri, A, Dar, AA, Zaika, A, Kelley, M, El-Rifai, W. t-Darpp promotes cancer cell survival by up-regulation of Bcl2 through Akt-dependent mechanism. Cancer Res, 68(2), 395-403, 2008.
Dar, AA, Zaika, A, Piazuelo, MB, Correa, P, Koyama, T, Belkhiri, A, Washington, K, Castells, A, Pera, M, El-Rifai, W. Frequent overexpression of Aurora Kinase A in upper gastrointestinal adenocarcinomas correlates with potent antiapoptotic functions. Cancer, 112(8), 1688-98, 2008.
Peng, D, Sheta, EA, Powell, SM, Moskaluk, CA, Washington, K, Goldknopf, IL, El-Rifai, W. Alterations in Barrett''s-related adenocarcinomas: a proteomic approach. Int J Cancer, 122(6), 1303-10, 2008.
Vilgelm, A, Wei, JX, Piazuelo, MB, Washington, MK, Prassolov, V, El-Rifai, W, Zaika, A. DeltaNp73alpha regulates MDR1 expression by inhibiting p53 function. Oncogene, 27(15), 2170-6, 2008.
Wei, J, O''Brien, D, Vilgelm, A, Piazuelo, MB, Correa, P, Washington, MK, El-Rifai, W, Peek, RM, Zaika, A. Interaction of Helicobacter pylori with gastric epithelial cells is mediated by the p53 protein family. Gastroenterology, 134(5), 1412-23, 2008. PMCID:2430883
Kuester, D, Dar, AA, Moskaluk, CC, Krueger, S, Meyer, F, Hartig, R, Stolte, M, Malfertheiner, P, Lippert, H, Roessner, A, El-Rifai, W, Schneider-Stock, R. Early involvement of death-associated protein kinase promoter hypermethylation in the carcinogenesis of Barrett''s esophageal adenocarcinoma and its association with clinical progression. Neoplasia, 9(3), 236-45, 2007. PMCID:1838580
Razvi, MH, Peng, D, Dar, AA, Powell, SM, Frierson, HF, Moskaluk, CA, Washington, K, El-Rifai, W. Transcriptional oncogenomic hot spots in Barrett''s adenocarcinomas: serial analysis of gene expression. Genes Chromosomes Cancer, 46(10), 914-28, 2007.
Lee, OJ, Hong, SM, Razvi, MH, Peng, D, Powell, SM, Smoklin, M, Moskaluk, CA, El-Rifai, W. Expression of calcium-binding proteins S100A2 and S100A4 in Barrett''s adenocarcinomas. Neoplasia, 8(10), 843-50, 2006. PMCID:1715926
Maqani, N, Belkhiri, A, Moskaluk, C, Knuutila, S, Dar, AA, El-Rifai, W. Molecular dissection of 17q12 amplicon in upper gastrointestinal adenocarcinomas. Mol Cancer Res, 4(7), 449-55, 2006.
McChesney, PA, Aiyar, SE, Lee, OJ, Zaika, A, Moskaluk, C, Li, R, El-Rifai, W. Cofactor of BRCA1: a novel transcription factor regulator in upper gastrointestinal
adenocarcinomas. Cancer Res, 66(3), 1346-53, 2006.
Tomkova, K, El-Rifai, W, Vilgelm, A, Kelly, MC, Wang, TC, Zaika, AI. The gastrin gene promoter is regulated by p73 isoforms in tumor cells. Oncogene, , , 2006.
Wu, Z, Siadaty, MS, Riddick, G, Frierson, HF, Lee, JK, Golden, W, Knuutila, S, Hampton, GM, El-Rifai, W, Theodorescu, D. A novel method for gene expression mapping of metastatic competence in human
bladder cancer. Neoplasia, 8(3), 181-9, 2006. PMCID:1578518
Zaika, AI, El-Rifai, W. The role of p53 protein family in gastrointestinal malignancies. Cell Death Differ, 13(6), 935-40, 2006.
Belkhiri, A, Zaika, A, Pidkovka, N, Knuutila, S, Moskaluk, C, El-Rifai, W. Darpp-32: a novel antiapoptotic gene in upper gastrointestinal carcinomas. Cancer Res, 65(15), 6583-92, 2005.
Johnson, AH, Frierson, HF, Zaika, A, Powell, SM, Roche, J, Crowe, S, Moskaluk, CA, El-Rifai, W. Expression of tight-junction protein claudin-7 is an early event in gastric
tumorigenesis. Am J Pathol, 167(2), 577-84, 2005. PMCID:1603560
Lee, OJ, Schneider-Stock, R, McChesney, PA, Kuester, D, Roessner, A, Vieth, M, Moskaluk, CA, El-Rifai, W. Hypermethylation and Loss of Expression of Glutathione Peroxidase-3 in Barrett''s
Tumorigenesis. Neoplasia, 7(9), 854-61, 2005. PMCID:1501938
Guti??rrez, MI, Siraj, AK, Khaled, H, Koon, N, El-Rifai, W, Bhatia, K. CpG island methylation in Schistosoma- and non-Schistosoma-associated bladder
cancer. Mod Pathol, 17(10), 1268-74, 2004.
Koon, N, Schneider-Stock, R, Sarlomo-Rikala, M, Lasota, J, Smolkin, M, Petroni, G, Zaika, A, Boltze, C, Meyer, F, Andersson, L, Knuutila, S, Miettinen, M, El-Rifai, W. Molecular targets for tumour progression in gastrointestinal stromal tumours. Gut, 53(2), 235-40, 2004. PMCID:1774925
Koon, N, Zaika, A, Moskaluk, CA, Frierson, HF, Knuutila, S, Powell, SM, El-Rifai, W. Clustering of molecular alterations in gastroesophageal carcinomas. Neoplasia, 6(2), 143-9, 2004. PMCID:1502088
Tomkova, K, Belkhiri, A, El-Rifai, W, Zaika, AI. p73 isoforms can induce T-cell factor-dependent transcription in gastrointestinal
cells. Cancer Res, 64(18), 6390-3, 2004.
Varis, A, Zaika, A, Puolakkainen, P, Nagy, B, Madrigal, I, Kokkola, A, V??yrynen, A, K??rkk??inen, P, Moskaluk, C, El-Rifai, W, Knuutila, S. Coamplified and overexpressed genes at ERBB2 locus in gastric cancer. Int J Cancer, 109(4), 548-53, 2004.
Wagner, KW, Sapinoso, LM, El-Rifai, W, Frierson, HF, Butz, N, Mestan, J, Hofmann, F, Deveraux, QL, Hampton, GM. Overexpression, genomic amplification and therapeutic potential of inhibiting
the UbcH10 ubiquitin conjugase in human carcinomas of diverse anatomic origin. Oncogene, 23(39), 6621-9, 2004.
Beckler, A, Moskaluk, CA, Zaika, A, Hampton, GM, Powell, SM, Frierson, HF, El-Rifai, W. Overexpression of the 32-kilodalton dopamine and cyclic adenosine 3'',5''-monophosphate-regulated
phosphoprotein in common adenocarcinomas. Cancer, 98(7), 1547-51, 2003.
Beckler, AD, Roche, JK, Harper, JC, Petroni, G, Frierson, HF, Moskaluk, CA, El-Rifai, W, Powell, SM. Decreased abundance of trefoil factor 1 transcript in the majority of gastric
carcinomas. Cancer, 98(10), 2184-91, 2003.
Berr, SS, Roche, JK, El-Rifai, W, Smith, MF, Powell, SM. Magnetic resonance imaging of gastric cancer in Tff1 knock-out mice. Magn Reson Med, 49(6), 1033-6, 2003.
Deng, D, El-Rifai, W, Ji, J, Zhu, B, Trampont, P, Li, J, Smith, MF, Powel, SM. Hypermethylation of metallothionein-3 CpG island in gastric carcinoma. Carcinogenesis, 24(1), 25-9, 2003.
Dematteo, RP, Heinrich, MC, El-Rifai, WM, Demetri, G. Clinical management of gastrointestinal stromal tumors: before and after STI-571. Hum Pathol, 33(5), 466-77, 2002.
El-Rifai, W, Moskaluk, CA, Abdrabbo, MK, Harper, J, Yoshida, C, Riggins, GJ, Frierson, HF, Powell, SM. Gastric cancers overexpress S100A calcium-binding proteins. Cancer Res, 62(23), 6823-6, 2002.
El-Rifai, W, Powell, SM. Molecular biology of gastric cancer. Semin Radiat Oncol, 12(2), 128-40, 2002.
El-Rifai, W, Smith, MF, Li, G, Beckler, A, Carl, VS, Montgomery, E, Knuutila, S, Moskaluk, CA, Frierson, HF, Powell, SM. Gastric cancers overexpress DARPP-32 and a novel isoform, t-DARPP. Cancer Res, 62(14), 4061-4, 2002.
Miettinen, M, El-Rifai, W, H L Sobin, L, Lasota, J. Evaluation of malignancy and prognosis of gastrointestinal stromal tumors:
a review. Hum Pathol, 33(5), 478-83, 2002.
Shuber, AP, Asca??o, JJ, Boynton, KA, Mitchell, A, Frierson, HF, El-Rifai, W, Powell, SM. Accurate, noninvasive detection of Helicobacter pylori DNA from stool samples:
potential usefulness for monitoring treatment. J Clin Microbiol, 40(1), 262-4, 2002. PMCID:120120
Varis, A, Wolf, M, Monni, O, Vakkari, ML, Kokkola, A, Moskaluk, C, Frierson, H, Powell, SM, Knuutila, S, Kallioniemi, A, El-Rifai, W. Targets of gene amplification and overexpression at 17q in gastric cancer. Cancer Res, 62(9), 2625-9, 2002.
el-Rifai, W, Powell, SM. Molecular and biologic basis of upper gastrointestinal malignancy. Gastric
carcinoma. Surg Oncol Clin N Am, 11(2), 273-91, viii, 2002.
Asca??o, JJ, Frierson, H, Moskaluk, CA, Harper, JC, Roviello, F, Jackson, CE, El-Rifai, W, Vindigni, C, Tosi, P, Powell, SM. Inactivation of the E-cadherin gene in sporadic diffuse-type gastric cancer. Mod Pathol, 14(10), 942-9, 2001.
El-Rifai, W, Frierson , HF, Moskaluk, CA, Harper, JC, Petroni, GR, Bissonette, EA, Jones, DR, Knuutila, S, Powell, SM. Genetic differences between adenocarcinomas arising in Barrett''s esophagus
and gastric mucosa. Gastroenterology, 121(3), 592-8, 2001.
El-Rifai, W, Frierson, HF, Harper, JC, Powell, SM, Knuutila, S. Expression profiling of gastric adenocarcinoma using cDNA array. Int J Cancer, 92(6), 832-8, 2001.
El-Rifai, W, Rutherford, S, Knuutila, S, Frierson, HF, Moskaluk, CA. Novel DNA copy number losses in chromosome 12q12--q13 in adenoid cystic carcinoma. Neoplasia, 3(3), 173-8, 2001. PMCID:1505590
Kettunen, E, Niss??n, AM, Ollikainen, T, Taavitsainen, M, Tapper, J, Mattson, K, Linnainmaa, K, Knuutila, S, El-Rifai, W. Gene expression profiling of malignant mesothelioma cell lines: cDNA array
study. Int J Cancer, 91(4), 492-6, 2001.
Kiuru-Kuhlefelt, S, El-Rifai, W, Fanburg-Smith, J, Kere, J, Miettinen, M, Knuutila, S. Concomitant DNA copy number amplification at 17q and 22q in dermatofibrosarcoma
protuberans. Cytogenet Cell Genet, 92(3-4), 192-5, 2001.
Tapper, J, Kettunen, E, El-Rifai, W, Sepp??l??, M, Andersson, LC, Knuutila, S. Changes in gene expression during progression of ovarian carcinoma. Cancer Genet Cytogenet, 128(1), 1-6, 2001.
El-Rifai, W, Kamel, D, Larramendy, ML, Shoman, S, Gad, Y, Baithun, S, El-Awady, M, Eissa, S, Khaled, H, Soloneski, S, Sheaff, M, Knuutila, S. DNA copy number changes in Schistosoma-associated and non-Schistosoma-associated
bladder cancer. Am J Pathol, 156(3), 871-8, 2000. PMCID:1876852
El-Rifai, W, Sarlomo-Rikala, M, Andersson, LC, Knuutila, S, Miettinen, M. DNA sequence copy number changes in gastrointestinal stromal tumors: tumor
progression and prognostic significance. Cancer Res, 60(14), 3899-903, 2000.
El-Rifai, W, Sarlomo-Rikala, M, Andersson, LC, Miettinen, M, Knuutila, S. High-resolution deletion mapping of chromosome 14 in stromal tumors of the
gastrointestinal tract suggests two distinct tumor suppressor loci. Genes Chromosomes Cancer, 27(4), 387-91, 2000.
Kettunen, E, el-Rifai, W, Bj??rkqvist, AM, Wolff, H, Karjalainen, A, Anttila, S, Mattson, K, Husgafvel-Pursiainen, K, Knuutila, S. A broad amplification pattern at 3q in squamous cell lung cancer--a fluorescence
in situ hybridization study. Cancer Genet Cytogenet, 117(1), 66-70, 2000.
Wolf, M, El-Rifai, W, Tarkkanen, M, Kononen, J, Serra, M, Eriksen, EF, Elomaa, I, Kallioniemi, A, Kallioniemi, OP, Knuutila, S. Novel findings in gene expression detected in human osteosarcoma by cDNA microarray. Cancer Genet Cytogenet, 123(2), 128-32, 2000.
Knuutila, S, Aalto, Y, Autio, K, Bj??rkqvist, AM, El-Rifai, W, Hemmer, S, Huhta, T, Kettunen, E, Kiuru-Kuhlefelt, S, Larramendy, ML, Lushnikova, T, Monni, O, Pere, H, Tapper, J, Tarkkanen, M, Varis, A, Wasenius, VM, Wolf, M, Zhu, Y. DNA copy number losses in human neoplasms. Am J Pathol, 155(3), 683-94, 1999. PMCID:1866903
Plass, C, Yu, F, Yu, L, Strout, MP, El-Rifai, W, Elonen, E, Knuutila, S, Marcucci, G, Young, DC, Held, WA, Bloomfield, CD, Caligiuri, MA. Restriction landmark genome scanning for aberrant methylation in primary refractory
and relapsed acute myeloid leukemia; involvement of the WIT-1 gene. Oncogene, 18(20), 3159-65, 1999.
Zhu, Y, Monni, O, El-Rifai, W, Siitonen, SM, Vilpo, L, Vilpo, J, Knuutila, S. Discontinuous deletions at 11q23 in B cell chronic lymphocytic leukemia. Leukemia, 13(5), 708-12, 1999.
el-Rifai, W, Tarmo, L, Hemmer, S, F??rsti, A, Pedersen, N, Lichtenstein, P, Ahlbom, A, S??derberg, M, Knuutila, S, Hemminki, K. DNA copy number losses at 1p32-pter in monozygotic twins concordant for breast
cancer. Cancer Genet Cytogenet, 112(2), 169-72, 1999.
El-Rifai, W, Harper, JC, Cummings, OW, Hyytinen, ER, Frierson, HF, Knuutila, S, Powell, SM. Consistent genetic alterations in xenografts of proximal stomach and gastro-esophageal
junction adenocarcinomas. Cancer Res, 58(1), 34-7, 1998.
El-Rifai, W, Sarlomo-Rikala, M, Knuutila, S, Miettinen, M. DNA copy number changes in development and progression in leiomyosarcomas of
soft tissues. Am J Pathol, 153(3), 985-90, 1998. PMCID:1853026
Kiuru-Kuhlefelt, S, El-Rifai, W, Sarlomo-Rikala, M, Knuutila, S, Miettinen, M. DNA copy number changes in alveolar soft part sarcoma: a comparative genomic
hybridization study. Mod Pathol, 11(3), 227-31, 1998.
Knuutila, S, Armengol, G, Bj??rkqvist, AM, el-Rifai, W, Larramendy, ML, Monni, O, Szymanska, J. Comparative genomic hybridization study on pooled DNAs from tumors of one clinical-pathological
entity. Cancer Genet Cytogenet, 100(1), 25-30, 1998.
Knuutila, S, Bj??rkqvist, AM, Autio, K, Tarkkanen, M, Wolf, M, Monni, O, Szymanska, J, Larramendy, ML, Tapper, J, Pere, H, El-Rifai, W, Hemmer, S, Wasenius, VM, Vidgren, V, Zhu, Y. DNA copy number amplifications in human neoplasms: review of comparative genomic
hybridization studies. Am J Pathol, 152(5), 1107-23, 1998. PMCID:1858578
Larramendy, ML, El-Rifai, W, Knuutila, S. Comparison of fluorescein isothiocyanate- and Texas red-conjugated nucleotides
for direct labeling in comparative genomic hybridization. Cytometry, 31(3), 174-9, 1998.
Larramendy, ML, Huhta, T, Vettenranta, K, El-Rifai, W, Lundin, J, Pakkala, S, Saarinen-Pihkala, UM, Knuutila, S. Comparative genomic hybridization in childhood acute lymphoblastic leukemia. Leukemia, 12(10), 1638-44, 1998.
Larramendy, ML, el-Rifai, W, Kokkola, A, Puolakkainen, P, Monni, O, Salovaara, R, Aarnio, M, Knuutila, S. Comparative genomic hybridization reveals differences in DNA copy number changes
between sporadic gastric carcinomas and gastric carcinomas from patients with hereditary nonpolyposis
colorectal cancer. Cancer Genet Cytogenet, 106(1), 62-5, 1998.
Sarlomo-Rikala, M, El-Rifai, W, Lahtinen, T, Andersson, LC, Miettinen, M, Knuutila, S. Different patterns of DNA copy number changes in gastrointestinal stromal tumors,
leiomyomas, and schwannomas. Hum Pathol, 29(5), 476-81, 1998.
el-Rifai, W, Sarlomo-Rikala, M, Andersson, LC, Miettinen, M, Knuutila, S. DNA copy number changes in gastrointestinal stromal tumors--a distinct genetic
entity. Ann Chir Gynaecol, 87(4), 287-90, 1998.
Billstr??m, R, Johansson, B, Str??mbeck, B, el-Rifai, W, Larramendy, M, Olofsson, T, Mitelman, F, Knuutila, S. Clonal CD5-positive B lymphocytes in myelodysplastic syndrome with systemic
vasculitis and trisomy 8. Ann Hematol, 74(1), 37-40, 1997.
El-Rifai, W, Elonen, E, Larramendy, M, Ruutu, T, Knuutila, S. Chromosomal breakpoints and changes in DNA copy number in refractory acute
myeloid leukemia. Leukemia, 11(7), 958-63, 1997.
El-Rifai, W, Ruutu, T, Elonen, E, Volin, L, Knuutila, S. Prognostic value of metaphase-fluorescence in situ hybridization in follow-up
of patients with acute myeloid leukemia in remission. Blood, 89(9), 3330-4, 1997.
El-Rifai, W, Ruutu, T, Vettenranta, K, Elonen, E, Saarinen, UM, Volin, L, Knuutila, S. Follow-up of residual disease using metaphase-FISH in patients with acute lymphoblastic
leukemia in remission. Leukemia, 11(5), 633-8, 1997.
Miettinen, MM, el-Rifai, W, Sarlomo-Rikala, M, Andersson, LC, Knuutila, S. Tumor size-related DNA copy number changes occur in solitary fibrous tumors
but not in hemangiopericytomas. Mod Pathol, 10(12), 1194-200, 1997.
Sulisalo, T, M??kitie, O, Sistonen, P, Ridanp????, M, el-Rifai, W, Ruuskanen, O, de la Chapelle, A, Kaitila, I. Uniparental disomy in cartilage-hair hypoplasia. Eur J Hum Genet, 5(1), 35-42, 1997.
el-Rifai, W, Larramendy, ML, Bj??rkqvist, AM, Hemmer, S, Knuutila, S. Optimization of comparative genomic hybridization using fluorochrome conjugated
to dCTP and dUTP nucleotides. Lab Invest, 77(6), 699-700, 1997.
El-Rifai, W, Larramendy, ML, Ruutu, T, Knuutila, S. Lymphoid involvement in a patient with acute myeloid leukemia: a direct phenotypic
and genotypic study of single cells. Genes Chromosomes Cancer, 15(1), 34-7, 1996.
Mertens, F, P?Ylsson, E, Lindstrand, A, Toksvig-Larsen, S, Knuutila, S, Larramendy, ML, el-Rifai, W, Limon, J, Mitelman, F, Mandahl, N. Evidence of somatic mutations in osteoarthritis. Hum Genet, 98(6), 651-6, 1996.
Slunga-Tallberg, A, el-Rifai, W, Kein??nen, M, Ylinen, K, Kurki, T, Klinger, K, Ylikorkala, O, Larramendy, ML, Knuutila, S. Maternal origin of transferrin receptor positive cells in venous blood of pregnant
women. Clin Genet, 49(4), 196-9, 1996.
el Rifai, W, Knuutila, S. Fluorescent in situ hybridization on archival G-banded slides. Cytogenet Cell Genet, 73(4), 322-4, 1996.
el-Rifai, W, Ruutu, T, Vettenranta, K, Temtamy, S, Knuutila, S. Minimal residual disease after allogeneic bone marrow transplantation for chronic
myeloid leukaemia: a metaphase-FISH study. Br J Haematol, 92(2), 365-9, 1996.
el-Rifai, W, Sarlomo-Rikala, M, Miettinen, M, Knuutila, S, Andersson, LC. DNA copy number losses in chromosome 14: an early change in gastrointestinal
stromal tumors. Cancer Res, 56(14), 3230-3, 1996.
Knuutila, S, Larramendy, ML, Elfving, P, el-Rifai, W, Miettinen, A, Mitelman, F. Trisomy 7 in non-neoplastic tubular epithelial cells of the kidney. Hum Genet, 95(2), 149-56, 1995.
Larramendy, M, el-Rifai, W, Saarinen, U, Alitalo, R, Luomahaara, S, Knuutila, S. Myeloid lineage involvement in acute lymphoblastic leukemia: a morphology antibody
chromosomes (MAC) study. Exp Hematol, 23(14), 1563-7, 1995.
Slunga-Tallberg, A, el-Rifai, W, Kein??nen, M, Ylinen, K, Kurki, T, Klinger, K, Ylikorkala, O, Knuutila, S. Maternal origin of nucleated erythrocytes in peripheral venous blood of pregnant
women. Hum Genet, 96(1), 53-7, 1995.
el-Rifai, W, Leisti, J, K??hk??nen, M, Pietarinen, A, Altherr, MR, Knuutila, S. A patient with Wolf-Hirschhorn syndrome originating from translocation t(4;8)
(p16.3;q24.3)pat. J Med Genet, 32(1), 65-7, 1995. PMCID:1050183
el-Rifai, W, Pettersson, T, Larramendy, ML, Knuutila, S. Lineage involvement and karyotype in a patient with myelodysplasia and blood
basophilia. Eur J Haematol, 53(5), 288-92, 1994.
A post-doctoral position is available in Dr. El-Rifai Laboratory, laboratories of Surgical Oncology and Cancer Biology. The laboratory is well equipped with access to outstanding core facilities at the University of Vanderbilt School of Medicine and Cancer Center. University of Vanderbilt School of Medicine is one of the top academic institutes in the US.
The laboratory is focused on understanding the molecular events in development and progression of gastric and esophageal cancer as well as drug resistance and targeted therapy approaches. A list of the laboratory publications and interests can be viewed at:
There is particular interest in understanding the signaling mechanism of novel molecular targets that are related to apoptosis and drug resistance. Candidates with experience in cancer genetics, epigenetics, molecular biology, and cell biology techniques are encouraged to apply. Candidates should have excellent experience dealing with cell lines, and performing basic molecular biology techniques such as real time RT PCR, Western blots, EMSA, ChIP, and immunofluorescence. An experience in working with animal models is desired. Applicants must have experience in two or more of the areas of interest that are outlined above, in order to be considered. Salaries are highly competitive and commensurate with experience. Candidates should have a Ph.D or equivalent.
Candidates with publications in peer-reviewed journals are strongly encouraged to apply. Send curriculum vitae, statement of research interest, and names and contact information of at least two references.
Vanderbilt University is committed to principles of equal opportunity and affirmative action.
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