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Ralph B. Arlinghaus, Ph.D.

Present Title & Affiliation

Primary Appointment

Professor, Department Chair, Department of Molecular Pathology, Division of Pathology/Lab Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX
Hubert L. Stringer Chair in Cancer Research, The University of Texas MD Anderson Cancer Center, Houston, TX

Dual/Joint/Adjunct Appointment

Member of the Graduate Faculty, The University of Texas Graduate School of Biomedical Sciences, Houston, TX

Education & Training

Degree-Granting Education

1961 University of Cincinnati, College of Medicine, Cincinnati, OH, PHD, Biochemistry
1959 University of Cincinnati, Graduate School of Arts, Cincinnati, OH, MS, Pharmaceutical Chem
1957 University of Cincinnati, College of Pharmacy, Cincinnati, OH, BS, Pharmacy

Experience/Service

Academic Appointments

Professor, Chair, Deputy Division Head, Department of Molecular Pathology, Division of Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, 7/1986-8/1998
Visiting Investigator (Member), Scripps Clinic & Research Foundation, LaJolla, CA, 1/1983-1/1986
Professor, Chair Ad Interim, Deputy Division Head, Department of Tumor Virology, U.T. System Cancer Center, M. D. Anderson Hospital & Tumor Institute, Houston, TX, 1/1976-1/1983

Institutional Committee Activities

Member, Animal Research Science Advisory Committee, 9/2006-present
Member, Executive Committee of the Science Faculty, 2001-present

Selected Publications

Peer-Reviewed Original Research Articles
1. Shi P, Chandra J, Sun X, Gergely M, Cortes J, Garcia-Manera G, Arlinghaus R, Lai R, Amin H. Inhibition of IGF-IR tyrosine kinase induces apoptosis and cell cycle arrest in imatinib-resistant chronic myeloid leukemia cells. J Cell Mol Med(6B):1777-92, 6/2010. e-Pub 6/2009. PMCID: PMC19508387.
2. Samanta AK, Chakraborty SN, Wang Y, Schlette E, Reddy ER, Arlinghaus RB. Destabilization of Bcr-Abl/Jak2 network by a Jak2/Abl kinase inhibitor ON044580 overcomes drug resistance in blast crisis chronic myelogenous leukemia (CML). Genes & Cancer 1(4):346-59, 5/2010. PMCID: PMC2927857.
3. Leng X, Ding T, Lin H, Wang Y, Lin F, Zen B, Hu L, Yan K, Xing Y, Qi Y, Anderson K, Hu J, Feig B, Chiao P, Zhang W, Pusztai L, Symmans WF, Wu Y, Arlinghaus RB. Inhibition of Lipocalin 2 Impairs Breast Tumorigenesis and Metastasis. Cancer Res 69(22):8579-84, 11/2009. e-Pub 11/2009. PMID: 19887608.
4. Hu L, Hittelman W, Lu T, Ji P, Arlinghaus R, Shmulevich I, Hamilton SR, Zhang W. NGAL decreases E-cadherin-mediated cell-cell adhesion and increases cell motility and invasion through Rac1 in colon carcinoma cells. Lab Invest 89(5):531-48, 5/2009. e-Pub 3/2009. PMID: 19308044.
5. Samanta AK, Chakraborty, SN, Wang Y, Kantarjian H, Sun X, Perrotti D, Hood J, Arlinghaus RB. Jak2 inhibition deactivates Lyn kinase through the SET-PP2A-SHP1 pathway causing apoptosis in drug-resistant cells from chronic myelogenous leukemia patients. Oncogene 28(14):1669-81, 4/2009. e-Pub 2/2009. PMID: 19234487.
6. Muehlberg F, Song YH, Krohn A, Pinilla S, Droll L, Leng X, Seidensticker M, Ricke J, Altman A, Devarajan E, Liu W, Arlinghaus R, Alt E.. Tissue resident stem cells promote breast cancer growth and metastasis. Carcinogenesis 30(4):588-97, 4/2009. e-Pub 1/2009. PMID: 19181699.
7. Leng X, Lin H, Ding T, Wang Y, Wu Y, Klumpp S, Monaco P, Belmont J, Aderem A, Akira S, Strong R, Arlinghaus RB. Lipocalin 2 is required for BCR-ABL-induced tumorigenesis. Oncogene 27(47):6110-9, 10/2008. e-Pub 7/2008. PMCID: PMC2756829.
8. Tao W, Lin H, Sun T, Arlinghaus R. BCR-ABL oncogenic transformation of NIH 3T3 fibroblasts requires the IL-3 receptor. Oncogene 27(22):3194-200, 5/2008. e-Pub 12/2007. PMCID: PMC2756828.
9. Zhang H, Trachootham D, Lu W, Carew J, Giles FJ, Keating MJ, Arlinghaus RB, Huang P. Effective Killing of Gleevec-Resistant CML-Cells with T3151 Mutation by a Natural Compound PEITC through Redox-Mediated Mechanism. Leukemia 22(6):1191-9, 4/2008. PMCID: PMC18385754.
10. Perazzona B, Lin H, Sun T, Wang Y, Arlinghaus R. Kinase domain mutants of Bcr enhance Bcr-Abl oncogenic effects. Oncogene 27(15):2208-14, 4/2008. e-Pub 10/2007. PMCID: PMC2585769.
11. Arlinghaus R, Leng X. Requirement of lipocalin 2 for chronic myeloid leukemia. Leuk Lymphoma 49(4):600-3, 4/2008. PMID: 18398717.
12. Ban K, Gao Y, Amin HM, Howard A, Miller C, Lin Q, Leng X, Munsell M, Bar-Eli M, Arlinghaus RB Chandra J. BCR-ABL1 Mediates Up-Regulation of Fyn in Chronic Myelogenous Leukemia. Blood 111(5):2904-8, 3/2008. e-Pub 1/2008. PMCID: PMC2254539.
13. Tari, AM, Gutierrez-Puente, Y, Monaco G, Stephens C, Sun T, Rosenblum M, Belmont J, Arlinghaus RB, Lopez-Berestein G. Liposome-incorporated Grb2 antisense oligodeoxynucleotide increases the survival of mice bearing bcr-abl-positive leukemia xenografts. Int J Oncol 31(5):1243-50, 11/2007. PMID: 17912453.
14. Saldanha J, Silvy M, Beaufils N, Arlinghaus R, Barbany G, Branford S, Cayuela JM, Cazzaniga G, Gonzalez M, Grimwade D, Kairisto V, Miyamura K, Lawler M, Lion T, Macintyre E, Mahon FX, Muller MC, Ostergaard M, Pfeifer H, Saglio G, Sawyers C, Spinelli O, van der Velden VH, Wang JQ, Zoi K, Patel V, Phillips P, Matejtschuk P, Gabert J. Characterization of a reference material for BCR-ABL (M-BCR) mRNA quantitation by real-time amplification assays: towards new standards for gene expression measurements. Leukemia 21(7):1481-7, 7/2007. PMCID: PMC17476280.
15. Lin J, Sun T, Ji L, Deng W, Roth J, Minna J, Arlinghaus R. Oncogenic activation of c-Abl in non-small cell lung cancer cells lacking FUS1 expression: inhibition of c-Abl by the tumor suppressor gene product Fus1. Oncogene 26(49):6989-96, 5/2007. e-Pub 5/2007. PMCID: PMC17486070.
16. Trachootham D, Zhou Y, Zhang H, Demizu Y, Chen Z, Pelicano H, Chiao PJ, Achanta G, Arlinghaus RB, Liu J, Huang P. Selective killing of oncogenically transformed cells through a ROS-mediated mechanism by beta-phenylethyl isothiocyanate. Cancer Cell 10(3):241-52, 9/2006. PMID: 16959615.
17. Samanta AK, Lin H, Sun T, Kantarjian H, Arlinghaus RB. Janus kinase 2: a critical target in chronic myelogenous leukemia. Cancer Res 66(13):6468-72, 7/2006. PMID: 16818614.
18. Ling, X., Wang, Y., Dietrich, M.F., Andreeff, M., Arlinghaus, R.B. Vaccination with Leukemia cells expressing cell surface-associated GM-CSF blocks leukemia induction in immunocompetent mice. Oncogene 25(32):4483-90, 7/2006. PMCID: PMC16547503.
19. Verstovsek S, Golemovic M, Kantarjian H, Manshouri T, Estrov Z, Manley P, Sun T, Arlinghaus RB, Alland L, Dugan M, Cortes J, Giles F, Beran M. AMN107, a novel aminopyrimidine inhibitor of p190 Bcr-Abl activation and of in vitro proliferation of Philadelphia-positive acute lymphoblastic leukemia cells. Cancer 104(6):1230-6, 9/2005. PMID: 16078266.
20. Golemovic M, Verstovsek S, Giles F, Cortes J, Manshouri T, Manley PW, Mestan J, Dugan M, Alland L, Griffin JD, Arlinghaus RB, Sun T, Kantarjian H, Beran M. AMN107, a novel aminopyrimidine inhibitor of Bcr-Abl, has in vitro activity against imatinib-resistant chronic myeloid leukemia. Clin Cancer Res 11(13):4941-7, 7/2005. PMID: 16000593.
21. Lin H, Monaco G, Sun T, Ling X, Stephens C, Xie S, Belmont J, Arlinghaus RB. Bcr-Abl-mediated suppression of normal hematopoiesis in leukemia. Oncogene 24(20):3246-56, 5/2005. PMID: 15735695.
22. Ling X, Arlinghaus RB. Knockdown of STAT3 expression by RNA interference inhibits the induction of breast tumors in immunocompetent mice. Cancer Res 65(7):2532-6, 4/2005. PMID: 15805244.
23. Donato NJ, Wu JY, Stapley J, Lin H, Arlinghaus R, Aggarwal BB, Shishodia S, Albitar M, Hayes K, Kantarjian H, Talpaz M. Imatinib mesylate resistance through BCR-ABL independence in chronic myelogenous leukemia. Cancer Res 64(2):672-7, 1/2004. PMID: 14744784.
24. Katayama H, Sasai K, Kawai H, Yuan ZM, Bondaruk J, Suzuki F, Fujii S, Arlinghaus RB, Czerniak BA, Sen S. Phosphorylation by aurora kinase A induces Mdm2-mediated destabilization and inhibition of p53. Nat Genet 36(1):55-62, 1/2004. e-Pub 12/2003. PMID: 14702041.
25. Wang L, Duke L, Zhang PS, Arlinghaus RB, Symmans WF, Sahin A, Mendez R, Dai JL. Alternative splicing disrupts a nuclear localization signal in spleen tyrosine kinase that is required for invasion suppression in breast cancer. Cancer Res 63(15):4724-30, 8/2003. PMID: 12907655.
26. Mahon GM, Wang Y, Korus M, Kostenko E, Cheng L, Sun T, Arlinghaus RB, Whitehead IP. The c-Myc Oncoprotein Interacts with Bcr. Curr Biol 13(5):437-41, 3/2003. PMID: 12620195.
27. Ling X, Ma G, Sun T, Liu J, Arlinghaus RB. Bcr and Abl interaction: oncogenic activation of c-Abl by sequestering Bcr. Cancer Res 63(2):298-303, 1/2003. PMID: 12543778.
28. Donato NJ, Wu JY, Stapley J, Gallick G, Lin H, Arlinghaus R, Talpaz M. BCR-ABL independence and LYN kinase overexpression in chronic myelogenous leukemia cells selected for resistance to STI571. Blood 101(2):690-8, 1/2003. PMID: 12509383.
29. Kantarjian HM, Cortes JE, O'Brien S, Giles F, Garcia-Manero G, Faderl S, Thomas D, Jeha S, Rios MB, Letvak L, Bochinski K, Arlinghaus R, Talpaz M. Imatinib mesylate therapy in newly diagnosed patients with Philadelphia chromosome-positive chronic myelogenous leukemia: high incidence of early complete and major cytogenetic responses. Blood 101(1):97-100, 1/2003. e-Pub 8/2002. PMID: 12393600.
30. Kantarjian HM, Talpaz M, Cortes J, O'Brien S, Faderl S, Thomas D, Giles F, Rios MB, Shan J, Arlinghaus R. Quantitative polymerase chain reaction monitoring of BCR-ABL during therapy with imatinib mesylate (STI571; gleevec) in chronic-phase chronic myelogenous leukemia. Clin Cancer Res 9(1):160-6, 1/2003. PMID: 12538464.
31. Arlinghaus RB. Bcr: a negative regulator of the Bcr-Abl oncoprotein in leukemia. Oncogene 21(56):8560-7, 12/2002. PMID: 12476302.
32. Xie, S, Lin H, Sun T, Arlinghaus RB. Jak2 is involved in c-Myc induction by Bcr-Abl. Oncogene 21(47):7137-46, 10/2002. PMID: 12370803.
33. Kantarjian HM, O'Brien S, Cortes JE, Giralt SA, Rios MB, Shan J, Giles FJ, Thomas DA, Faderl S, De Lima M, Garcia-Manero G, Champlin R, Arlinghaus R, Talpaz M. Imatinib mesylate therapy for relapse after allogeneic stem cell transplantation for chronic myelogenous leukemia. Blood 100(5):1590-5, 9/2002. PMID: 12176876.
34. Atallah E, Talpaz M, O'Brien S, Rios MB, Guo JQ, Arlinghaus R, Fernandes-Reese S, Kantarjian H. Chronic myelogenous leukemia in T cell lymphoid blastic phase achieving durable complete cytogenetic and molecular remission with imatinib mesylate (STI571; Gleevec) therapy. Cancer 94(11):2996-9, 6/2002. PMID: 12115389.
35. Verstovsek S, Lin H, Kantarjian H, Saglio G, De Micheli D, Pane F, Garcia-Manero G, Intrieri M, Rotoli B, Salvatore F, Guo JQ, Talpaz M, Specchia G, Pizzolo G, Liberati AM, Cortes J, Quackenbush RC, Arlinghaus RB. Neutrophilic-chronic myeloid leukemia: low levels of p230 BCR/ABL mRNA and undetectable BCR/ABL protein may predict an indolent course. Cancer 94(9):2416-25, 5/2002. PMID: 12015767.
36. Tan M, Jing T, Lan KH, Neal CL, Li P, Lee S, Fang D, Nagata Y, Liu J, Arlinghaus R, Hung MC, Yu D. Phosphorylation on tyrosine-15 of p34(Cdc2) by ErbB2 inhibits p34(Cdc2) activation and is involved in resistance to taxol-induced apoptosis. Mol Cell 9(5):993-1004, 5/2002. PMID: 12049736.
37. Lin H, Guo JQ, Andreeff M, Arlinghaus RB. Detection of dual TEL-ABL transcripts and a Tel-Abl protein containing phosphotyrosine in a chronic myeloid leukemia patient. Leukemia 16(2):294-7, 2/2002. PMID: 11840298.
38. Hawk N, Sun T, Xie S, Wang Y, Wu Y, Liu J, Arlinghaus RB. Inhibition of the Bcr-Abl oncoprotein by Bcr requires phosphoserine 354. Cancer Res 62(2):386-90, 1/2002. PMID: 11809685.
39. Arlinghaus RB. The Involvement of Bcr in leukemias with the Philadelphia Chromosome. Critical Reviews in Oncogenesis 1:1-18, 9/1998.
40. Wu Y, Liu J, Arlinghaus RB. Requirement of two specific tyrosine residues for the catalytic activity of Bcr serine/threonine kinase. Oncogene 16:141-6, 1/1998. PMID: 9467953.
41. Liu J, Wu Y, Arlinghaus RB. Sequences within the first exon of BCR inhibit the activated tyrosine kinases of c-Abl and the Bcr-Abl oncoprotein. Cancer Res 56:5120-4, 11/1996. PMID: 8912843.
42. Wilson-Rawls J, Xie S, Liu J, Laneuville P, Arlinghaus RB. P210 Bcr-Abl interacts with the interleukin 3 receptor beta(c) subunit and constitutively induces its tyrosine phosphorylation. Cancer Res 56:3426-30, 8/1996. PMID: 8758906.

Invited Articles
1. Leng X, Wu Y, Arlinghaus RB. Relationships of Lipocalin 2 with Breast Tumorigenesis and Metastasis. Journal of Cellular Physiology. e-Pub 9/2010. PMID: 20857428.
2. Lin J, and Arlinghaus RB. Activated c-Abl tyrosine kinase in malignant solid tumors. Oncogene 27(32):4385-91, 4/2008.
3. Guo JQ, Lian J, Xian YM, Arlinghaus RB. Enhanced detection of BCR-ABL protein in blood cells of Philadelphia chromsome positive leukemia patients using ECL. Amersham Corporation, Arlington Heights, IL. 2006.

Book Chapters
1. Arlinghaus RB. Involvement of the abl proto-oncogene in human leukemias. In: Genes and Cancer. John Wiley & Sons, Ltd. London, England, 65-71. Chapter 6, 2006.
2. Arlinghaus RB, Sun T. Signal transduction pathways in Bcr-Abl transformed cells. In: Cancer Treat Res. 119. Kluwer Academic Publishers: Norwell, MA, 119:239-70, 2004. PMID: 15164881.

Grant & Contract Support

Title: Interfering Breast Cancer Metastasis by Blocking NGAL Function
Funding Source: Susan G. Komen Breast Cancer Foundation
Role: Co- Principal Investigator
Principal Investigator: Wu
Duration: 9/1/2008 - 8/31/2011
 
Title: Proposal for in vitro studies of HSP 90 inhibitor, AUY922 and BEP800, in the context of its potential to increase AMN107 activity in CM: and PH-positive ALL
Funding Source: Novartis Pharmaceuticals
Role: Principal Investigator
Duration: 11/6/2006 - 3/31/2010
 
Title: A non-ATP competitive inhibitor or BCR-ABL for the therapy of imatinib-resistant CMLs(one year extension without funding)
Funding Source: DOD U.S. Army subcontract w/ Temple University
Role: PI of Subcontract
Principal Investigator: Premkumar Reddy, M.D.
Duration: 4/1/2006 - 3/31/2010
 
Title: Therapy of CML: Molecular mechanisms of Bcr-Abl oncogenesis (no cost extension through 2/28/10)
Funding Source: NIH/NCI
Role: Project Director
Principal Investigator: Richard Champlin, M.D.
Duration: 9/1/1998 - 2/28/2010

Last updated: 11/30/2010