Pathology and Microbiology

Timothy C. Greiner, M.D.

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ACADEMIC DEGREES:

Medical/Graduate School:
M.S., Preventive Medicine and Environmental Health, University of Iowa Graduate College, August 1981-December 1983
Doctor of Medicine, University of Iowa College of Medicine, Iowa City, Iowa, August 1982-May 1986
Residency/ Post-doctoral Fellowship Training:
Pathology Residency, Combined Anatomic and Clinical Pathology, University of Iowa Hospitals and Clinics, Iowa City, IA, July 1986 - June 1991
Research Fellowship, Molecular Pathology, University of Iowa, Iowa City, IA, October 1989 to September 1990.
Hematopathology Fellowship, National Cancer Institute/National Institutes of Health, Bethesda, MD, July 1991 - September 1993

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Contact name: Timothy Greiner, M.D.
Phone Number: 402-559-8707 ofc
                        402-559-6018 fax
                        888-1664 pager
e-mail address: tgreiner@unmc.edu

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• GRANT SUPPORT (last 3 years):

Molecular Signatures to Improve Diagnosis and Outcome Prediction in NHL, National Cancer Institute, P.I.: W. C. Chan, $9,000,000, 6/1/05-4/30/10, 2%, (Co-I: Timothy C. Greiner)

The Role of Mdm2 in Lymphoma Development, National Institute of Health, 7/03-7/08), 5%, P.I.: Christine Eischen, Ph.D. (Co-I: Timothy C. Greiner, M.D)

Methylation Analysis in Mantle Cell Lymphoma, Lymphoma Research Foundation, $620,000, 2/1/04-1/31/07, 10%, P.I.: Timothy C. Greiner, M.D. (Co-I: J. Christman, W.C. Chan, D.D. Weisenburger)

p53 Mutation Analysis in OL1-p53 Trial, ELEOS, Inc., $6,000, P.I.: Timothy C. Greiner, M.D., 7/04-6/06

MMP Regulation by Doxycycline in Aortic Aneurysm, National Institute of Health, HL62400-02, $752,379, 2000 – 2005, 5%, P.I. B. Timothy Baxter, M.D.

Analysis of Posttransplant Lymphomas by cDNA Microarray, Leukemia and Lymphoma Society,September 1, 2000 – August 31, 2003, $300,000, P.I. Timothy C. Greiner, M.D., Translational Research Grant 6605-01

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• PUBLICATIONS (last 5 years):

Alizadeh AA, Eisen MB, Davis RE, Ma C, Lossos IS, Rosenwald A, Boldrick JC, Sabet H, Tran T, Yu X, Powell JI, Yang L, Marti GE, Moore T, Hudson J Jr, Lu L, Lewis DB, Tibshirani R, Sherlock G, Chan WC,

Greiner TC, Weisenburger DD, Armitage JO, Warnke R, Levy R, Wilson W, Grever MR, Byrd JC,  Botstein D, Brown PO, Staudt LM. Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling.  Nature 405:503-511, 2000. 

Greiner TC, Abou-Elella AA, Smir BN, Orazi A, Hinrichs S, Anderson J, Gross T, Bierman P, Hauke R.  Molecular Epidemiology of EBNA-1 Substrains of Epstein-Barr Virus in Posttransplant Lymphoproliferative Disorders Which Have Infrequent p53 Mutations. Leuk Lymphoma 38:563-576, 2000. 

Abou-Elella A, Shafer M, Wan X, Velanker M, Weisenburger D, Nathwani B, Gascoyne R, Greiner T, Chan W.  Lymphomas with Follicular and Monocytoid B-cell Components: Evidence for a Common Clonal Origin from Follicle Center Cells.  Am J Clin Pathol 114:516-522, 2000. 

Weisenburger DD, Vose JM, Greiner TC, Lynch JC, Chan WC, Bierman PJ, Dave BJ, Sanger WG, Armitage JO.  Mantle Cell Lymphoma.  A Clinicopathologic Study of 68 cases from the Nebraska Lymphoma Study Group.  Am J Hematol 64:190-196, 2000. 

Lossos IS, Okada C, Tibshirani R, Warnke R, Vose JM, Greiner TC, Allen J, Levy R.  Molecular Analysis of Immunoglobulin Genes in Diffuse Large Cell Lymphomas.  Blood 95:1797-1803, 2000. 

Vose JM, Bierman PJ, Weisenburger DD, Lynch JC, Bociek Y, Chan WC, Greiner TC, Armitage JO.  Autologous hematopoietic stem cell transplantation for mantle cell lymphoma. Biol Blood Marrow Transplant  6(6):640-5, 2000.          

Wan X, Tarantolo S, Orton DF, Greiner TC.  Primary extramedullary plasmacytoma in the atria of the heart.  Cardiovasc Pathol  10(3):137-9, 2001.  

Nollendorfs A, Greiner TC, Nagase H, Baxter BT. The expression and localization of membrane type-1 matrix melloproteinase in human abdominal aortic aneurysms. J Vasc Surg  34(2):316-22, 2001. 

Hauke R, Smir B, Greiner T, Bierman P, Tarantolo S, Anderson J, Shaw B, Armitage J. Clinical and pathological features of post-transplant proliferative disorders: influence on survival and response to treatment. Ann Oncol 12(6): 831-4, 2001.  

Sharp JG, Bishop MR, Copple B, Greiner TC, Iversen PL, Jackson JD, Joshi SS, Benner EJ, Mann SL, Rao AK, Vose JM.  Oligonucleotide Enhanced Cytotoxicity of Idarubicin for Lymphoma Cells.  Leuk Lymphoma, 42(3):417-27, 2001.  

Dave BJ, Nelson M, Pickering DL, Chan WC, Greiner TC, Weisenburger DD, Armitage JO, Sanger WG.  Cytogenetic Characterization of Diffuse Large Cell Lymphoma Using Multi-Color Fluorescence in situ hybridization. Cancer Genet Cytogenet 132(2):125-132, 2002.   

Huang JZ, Sanger WG, Greiner TC, Staudt LM, Weisenburger DD, Pickering DL, Lynch JC, Armitage JO, Warnk RA, Alizadeh  AA, Lossos IS, Levy R, Chan WC. The t(14;18) Defines A Unique Subset of Diffuse Large B-Cell Lymphoma With A Germinal Center B-Cell Gene Expression Profile. Blood  99:2285-2290, 2002.   

Vose JM, Weisenburger DW, Lynch JC, Bierman PJ; Chan JC, Bast M, Aoun P, Bociek G, Greiner T, Armitage JO, and the Nebraska Lymphoma Study Group.  CNOP for diffuse aggressive non-Hodgkin's lymphoma: The Nebraska Lymphoma Study Group.  Leuk Lymphoma 43(4):799-804, 2002.   

Rosenwald A, Wright G, Chan WC, Connors JM, Campo E, Fisher RI, Gascoyne RD, Muller-Hermelink HK, Smeland EB, Giltnane JM, Hurt EM, Zhao H, Averett L, Yang L, Wilson WH, Jaffe ES, Simon R, Klausner RD, Powell J, Duffey PL, Longo DL, Greiner TC, Weisenburger DD, Staudt LM.  The Use of Molecular Profiling to Predict Survival After Chemotherapy for Diffuse Large B-cell Lymphoma. New Engl J Med  346(25):1937-47, 2002. 

Greiner TC, Rubocki RJ.  Effectiveness of Capillary Electrophoresis Using Florescent Labeled Primers in Detecting T-Cell Receptor Gamma Gene Rearrangements. J Molec Diag 4(3):137-43, 2002.  

Longo GM, Xiong W, Greiner TC, Zhao Y, Fiotti N, Baxter BT. Matrix Metalloproteinases 2 and 9 Work in Concert to Produce Aortic Aneurysms. J Clin Invest 110(5):625-32, 2002.  

Lawnicki LC, Weisenburger DD, Aoun P, Chan WC, Wickert RS, Greiner TC. The t(14;18) and Bcl-2 Expression are Present in a Subset of Primary Cutaneous Follicular Lymphoma: Association With Lower Grade.  Am J Clin Path 118(5):765-72, 2002.  

Gutierrez M, Ibrahim  M, Dale J, Greiner T, Straus S, Bhatia K.  Discrete Alterations in the BZFL1 Promotor Identify Tumor and Non-Tumor Associated EBV.  J Natl Cancer Inst  94(23):1757-63, 2002. 

Fang NY, Greiner TC, Weisenburger DD, Chan WC, Vose J, Armitage JO, Mayer A, Pike BL, Collins FS, Hacia JG.  Oligonucleotide microarrays demonstrate the highest frequency of ATM mutations in the mantle cell subtype of lymphoma.  Proceedings of the National Academy of the Science (PNAS) 100(9):5372-7, 2003.   

Wan X, Cochran G, Greiner T.  Removal of Mercuric Chloride Deposits From B5 Fixed Tissue Will Affect the Performance of Immunoperoxidase Staining of Selected Antibodies.  Appl Immunohistochem Mol Morphol 11(1):92-5, 2003. 

Hans CP, Weisenburger DD, Vose JM, Hock LM, Lynch JC, Aoun P, Greiner TC, Chan WC, Bocieck RG, Bierman PJ, Armitage JO.  A Significant Diffuse Component Predicts for Inferior Survival in Grade 3 Lymphoma, But Cytological Subtypes Do Not Predict Survival. Blood 101(6):2363-7, 2003. 

Alt JR, Greiner TC, Cleveland JL, Eischen CM.  Profound Effect of Mdm2 Haplo-Insufficiency on Myc-Induced Apoptosis and Lymphomagenesis. EMBO 22(6):1442-50, 2003.  

Lawnicki LC, Rubocki RJ, Chan WC, Lytle DM, Greiner TC. The Distribution of Gene Segments in T-cell Receptor Gamma Gene Rearrangements Demonstrates the Need for Complete Primers Sets. J Molec Diag  5(2):82-7, 2003. 

Rosenwald A, Wright G, Wiestner A, Chan WC, Connors JM, and 34 other authors including Greiner TC, for the Lymphoma/Leukemia Molecular Profiling Project. The Proliferation Gene Expression Signature is a Quantitative Integrator of Oncogenic Events that Predicts Survival in Mantle Cell Lymphoma. Cancer Cell 3(2):185-97, 2003. 

Pan  Z, Shen Y, Du C, Zhou G, Rosenwald A, Staudt LM, Greiner TC, McKeithan TW, Chan WC.  Two newly characterized germinal center B-cell-associated genes, GCET1 and GCET2, have differential expression in normal and neoplastic B cells. Am J Pathol 163(1):135-44, 2003. 

Rosenwald A, Wright G, Leroy K, Yu X, Gaulard P, Gascoyne RD, Chan WC, Zhao T, Haioun C, Greiner TC, Weisenburger DD, Lynch JC, Vose J, Armitage JO, Staudt LM.  Molecular diagnosis of primary mediastinal B cell lymphoma identifies a clinically favorable subgroup of diffuse large B cell lymphoma related to Hodgkin lymphoma. J Exp Med Sep 15;198(6):851-62, 2003. 

Hans CP, Weisenburger DD, Greiner TC, Gascoyne RD, Delabie J, Ott G, Muller-Hermelink HK, Campo E, Braziel RM, Jaffe ES, Pan Z, Farinha P, Smith LM, Falini B, Banham AH, Rosenwald A, Staudt LM, Connors JM, Armitage JO, Chan WC. Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray. Blood 103(1):275-82, 2004. 

Xiong W, Zhao Y, Prall A, Greiner TC, Baxter BT. Key Roles of CD4+ Cells and IFN-gamma in the Development of Abdominal Aortic Aneurysms in a Murine Model. J Immunol 172(4):2607-12, 2004. 

Iqbal J, Sanger WG, Horsman DE, Rosenwald A, Pickering DL, Dave B, Dave S, Xiao L, Cao K, Zhu Q, Sherman S, Hans CP, Weisenburger DD, Greiner TC, Gascoyne RD, Ott G, Muller-Hermelink HK, Delabie J, Braziel RM, Jaffe ES, Campo E, Lynch JC, Connors JM, Vose JM, Armitage JO, Grogan TM, Staudt LM, Chan WC.  BCL2 translocation defines a unique tumor subset within the germinal center B-cell-like diffuse large B-cell lymphoma. Am J Pathol 165(1):159-66, 2004.

Huang JZ, Weisenburger DD, Vose JM, Greiner TC, Aoun P, Chan WC, Lynch JC, Bierman PJ, Armitage JO. Diffuse large B-cell lymphoma arising in nodular lymphocyte predominant Hodgkin lymphoma: a report of 21 cases from the Nebraska Lymphoma Study Group. Leuk Lymphoma 45(8):1551-7, 2004. 

Dave SS, Wright G, Tan B, Rosenwald A, Gascoyne RD, Chan WC, Fisher RI, Braziel RM, Rimsza LM, Grogan TM, Miller TP, LeBlanc M, Greiner TC, Weisenburger DD, Lynch JC, Vose J, Armitage JO, Smeland EB, Kvaloy S, Holte H, Delabie J, Connors JM, Lansdorp PM, Ouyang Q, Lister TA, Davies AJ, Norton AJ, Muller-Hermelink HK, Ott G, Campo E, Montserrat E, Wilson WH, Jaffe ES, Simon R, Yang L, Powell J, Zhao H, Goldschmidt N, Chiorazzi M, Staudt LM. Prediction of survival in follicular lymphoma based on molecular features of tumor-infiltrating immune cells. N Engl J Med 351(21):2159-69, 2004. 

Gross TG, Bucuvalas JC, Park JR, Greiner TC, Hinrich SH, Kaufman SS, Langnas AN, McDonald RA, Ryckman FC, Shaw BW, Sudan DL, Lynch JC. Low-dose chemotherapy for Epstein-Barr virus-positive post-transplantation lymphoproliferative disease in children after solid organ transplantation. J Clin Oncol 23(27):6481-8, 2005.  

Fu K, Weisenburger DD, Greiner TC, Dave S, Wright G, Rosenwald A, Chiorazzi M, Iqbal J, Gesk S, Siebert R, De Jong D, Jaffe ES, Wilson WH, Delabie J, Ott G, Dave BJ, Sanger WG, Smith LM, Rimsza L, Braziel RM, Muller-Hermelink HK, Campo E, Gascoyne RD, Staudt LM, Chan WC. Cyclin D1-negative mantle cell lymphoma: a clinicopathologic study based on gene expression profiling.  Blood 106(13):4315-21, 2005.  

Bea S, Zettl A, Wright G, Salaverria I, Jehn P, Moreno V, Burek C, Ott G, Puig X, Yang L, Lopez-Guillermo A, Chan WC, Greiner TC, Weisenburger DD, Armitage JO, Gascoyne RD, Connors JM, Grogan TM, Braziel R, Fisher RI, Smeland EB, Kvaloy S, Holte H, Delabie J, Simon R, Powell J, Wilson WH, Jaffe ES, Montserrat E, Muller-Hermelink HK, Staudt LM. Diffuse large B-cell lymphoma subgroups have distinct genetic profiles that influence tumor biology and improve gene-expression-based survival prediction. Blood 106(9):3183-90, 2005.   

Hans CP, Weisenburger DD, Greiner TC, Chan WC, Aoun P, Cochran GT, Pan Z, Smith LM, Lynch JC, Bociek RG, Bierman PJ, Vose JM, Armitage JO.  Expression of PKC-beta or cyclin D2 predicts for inferior survival in diffuse large B-cell lymphoma. Mod Pathol (10):1377-84, 2005. 

Iqbal J, Neppalli VT, Wright G, Dave BJ, Horsman DE, Rosenwald A, Lynch J, Hans CP, Weisenburger DD, Greiner TC, Gascoyne RD, Campo E, Ott G, Muller-Hermelink HK, Delabie J, Jaffe ES, Grogan TM, Connors JM, Vose JM, Armitage JO, Staudt LM, Chan WC. BCL2 expression is a prognostic marker for the activated B-cell-like type of diffuse large B-cell lymphoma. J Clin Oncol 24(6):961-8, 2006. 

Rimsza LM, Roberts RA, Campo E, Grogan TM, Bea S, Salaverria I, Zettl A, Rosenwald A, Ott G, Muller-Hermelink K, Delabie J, Fisher RI, Unger JM, Leblanc M, Staudt LM, Jaffe ES, Gascoyne RD, Chan WC, Weisenburger DD, Greiner TC, Braziel RM, Miller TP. Loss of major histocompatibility class II expression in non-immune privileged site diffuse large B cell lymphoma is highly coordinated and not due to chromosomal deletions. Blood 107(3):1101-7, 2006.  

Greiner TC, Dasgupta C, Ho VV, Weisenburger DD, Smith LM, Lynch JC, Vose JM, Fu K, Armitage JO, Braziel RM, Campo E, Delabie J, Gascoyne RD, Jaffe ES, Muller-Hermelink HK, Ott G, Rosenwald A, Staudt LM, Im MY, Karaman MW, Pike BL, Chan WC, Hacia JG. Mutation and genomic deletion status of ataxia telangiectasia mutated (ATM) and p53 confer specific gene expression profiles in mantle cell lymphoma. Proc Natl Acad Sci USA 103(7):2352-7, 2006.

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• PREVIOUS GRADUATE STUDENTS/POST-DOCTORAL FELLOWS (present location):

Postdoctoral leve	Medical Students
Anne Tierens, M.D. - Researcher, Oslo, Norway	Desiree Langdell, M.D. Pathologist, Mayo
Bassam Smir, M.D. - Pathologist, N.C.	Yulia Demidovich, M.D. - Residency
Ashraf Abou-Elella - Pathologist, S.C.	David Scanlan, M.D. - Residency
Lyle Lawnicki, M.D. - Pathologist, WI
Kai Fu, M.D. - Pathologist, UNMC

 

Pathology Residents	Undergraduate Students
Cary Buresh, M.D., Pathologist, ID	Rick Mowery - DK
Poonam Sharma, M.D. - Pathologist, NE	Mike Ruma - Resdency
Xiaoying Wan, M.D. - Pathologiist, IN	Mike Brumm - Medical School

 

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ATM Mutations in Lymphoma.  We are collaborating with Joe Hacia, Ph.D. (USC), and have described the gene expression profiles of ATM mutations in mantle cell lymphoma utilizing an Affymetrix-based microarray system.  We plan to investigate the cause for the elevated ATM mutations and the effect in lymphoma development.

In 2006, we will begin using an ATM knockout mouse model to study the effect of environmental agents on the generation of abnormal hybrid T-cell receptor gamma-beta gene rearrangements.  

Gene Expression Analysis in Post-transplant Lymphoproliferative Disorders (PTLD).  In collaboration with Dr. Lou Staudt at the NCI, we have examined gene expression utilizing a cDNA microarray (Lymphochip) in PTLD.  We have studied 34 cases from this institution, and 10 cases from the University of Minnesota.  In addition, we have performed comparative genomic hybridization analysis on tumor DNA.  Comparative analyses will be performed between these disorders, infectious mononucleosis caused by Epstein Barr virus, and de novo subtypes of diffuse large cell lymphoma. 

Correlation of Gene Expression Array Data and Mutation Status in Diffuse Large Cell, Mantle Cell and Follicular Lymphoma.  In collaboration with Dr. John Chan, we are examining the gene expression patterns in the five major subtypes of lymphoma under the NCI Director’s Challenge “Towards a Molecular Classification of Tumors”.  Our laboratories are analyzing the p53 and bcl-6 mutation status in diffuse large cell lymphoma, and have published on ATM and p53 in mantle cell lymphoma to correlate with mRNA gene expression.  We aim to identify new targets or patterns of gene expression associated with mutation status.

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• SPECIALIZED LABORATORY/CLINICAL RESEARCH RESOURCES:

Mutation screening – we utilize both denaturing grading gel electrophoresis and the Transgenomic WAVE DNA fragment analysis system. Opticon real time PCR instrument and laser capture microdissection are also available.

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