Lori A. Hazlehurst, PhD

Our laboratory is focused on developing therapeutic strategies for targeting hematopoietic tumors in the context of the bone marrow microenvironment.  More recently the lab has been characterizing the role of CD44 and VLA-4 in mediating signaling and survival in the bone marrow.

• Schonbrunn E, Betzi S, Alam R, Martin MP, Becker A, Han H, Francis R, Chakrasali R, Jakkaraj S, Kazi A, Sebti SM, Cubitt CL, Gebhard AW, Hazlehurst LA, Tash JS, Georg GI. Development of Highly Potent and Selective Diaminothiazole Inhibitors of Cyclin-Dependent Kinases. J Med Chem. 2013 May. Pubmedid: 23600925.
• Nair RR, Tolentino JH, Argilagos RF, Zhang L, Pinilla-Ibarz J, Hazlehurst LA. Potentiation of Nilotinib-mediated cell death in the context of the bone marrow microenvironment requires a promiscuous JAK inhibitor in CML. Leuk Res. 2012 Jun;36(6):756-763. Pubmedid: 22209738. Pmcid: PMC3331955.
• Nair RR, Gebhard AW, Emmons MF, Hazlehurst LA. Emerging strategies for targeting cell adhesion in multiple myeloma. Adv Pharmacol. 2012;65:143-189. Pubmedid: 22959026.
• Nair RR, Tolentino JH, Hazlehurst LA. Role of STAT3 in Transformation and Drug Resistance in CML. Front Oncol. 2012;2:30. Pubmedid: 22649784. Pmcid: PMC3355894.
• Emmons MF, Gebhard AW, Nair RR, Baz R, McLaughlin ML, Cress AE, Hazlehurst LA. Acquisition of resistance toward HYD1 correlates with a reduction in cleaved α4 integrin expression and a compromised CAM-DR phenotype. Mol Cancer Ther. 2011 Dec;10(12):2257-2266. Pubmedid: 21980133. Pmcid: PMC3237739.
• Xiang Y, Remily-Wood ER, Oliveira V, Yarde D, He L, Cheng JQ, Mathews L, Boucher K, Cubitt C, Perez L, Gauthier TJ, Eschrich SA, Shain KH, Dalton WS, Hazlehurst L, Koomen JM. Monitoring a nuclear factor-κB signature of drug resistance in multiple myeloma. Mol Cell Proteomics. 2011 Nov;10(11):M110.005520. Pubmedid: 21846842. Pmcid: PMC3226396.
• Remily-Wood ER, Liu RZ, Xiang Y, Chen Y, Thomas CE, Rajyaguru N, Kaufman LM, Ochoa JE, Hazlehurst L, Pinilla-Ibarz J, Lancet J, Zhang G, Haura E, Shibata D, Yeatman T, Smalley KS, Dalton WS, Huang E, Scott E, Bloom GC, Eschrich SA, Koomen JM. A database of reaction monitoring mass spectrometry assays for elucidating therapeutic response in cancer. Proteomics Clin Appl. 2011 Aug;5(7-8):383-396. Pubmedid: 21656910. Pmcid: PMC3530891.
• Yanamandra N, Buzzeo RW, Gabriel M, Hazlehurst LA, Mari Y, Beaupre DM, Cuevas J. Tipifarnib-induced apoptosis in acute myeloid leukemia and multiple myeloma cells depends on Ca2+ influx through plasma membrane Ca2+ channels. J Pharmacol Exp Ther. 2011 Jun;337(3):636-643. Pubmedid: 21378206. Pmcid: PMC3101005.
• Padron E, Hazlehurst LE, Pinilla-Ibarz J. Molecular Pathogenesis of BCR-ABL in CML. Adv Malig Hematol. 2011;(62):71.
• Nair RR, Tolentino J, Hazlehurst LA. The bone marrow microenvironment as a sanctuary for minimal residual disease in CML. Biochem Pharmacol. 2010 Sep;80(5):602-612. Pubmedid: 20382130. Pmcid: PMC3285111.
• Yarde DN, Oliveira V, Mathews L, Wang X, Villagra A, Boulware D, Shain KH, Hazlehurst LA, Alsina M, Chen DT, Beg AA, Dalton WS. Targeting the Fanconi anemia/BRCA pathway circumvents drug resistance in multiple myeloma. Cancer Res. 2009 Dec;69(24):9367-9375. Pubmedid: 19934314.
• Turner JG, Marchion DC, Dawson JL, Emmons MF, Hazlehurst LA, Washausen P, Sullivan DM. Human multiple myeloma cells are sensitized to topoisomerase II inhibitors by CRM1 inhibition. Cancer Res. 2009 Sep;69(17):6899-6905. Pubmedid: 19690141. Pmcid: PMC2744372.
• Nair RR, Emmons MF, Cress AE, Argilagos RF, Lam K, Kerr WT, Wang HG, Dalton WS, Hazlehurst LA. HYD1-induced increase in reactive oxygen species leads to autophagy and necrotic cell death in multiple myeloma cells. Mol Cancer Ther. 2009 Aug;8(8):2441-2451. Pubmedid: 19671765. Pmcid: PMC2761715.
• Hazlehurst LA, Bewry NN, Nair RR, Pinilla-Ibarz J. Signaling networks associated with BCR-ABL-dependent transformation. Cancer Control. 2009 Apr;16(2):100-107. Pubmedid: 19337196.
• Shain KH, Yarde DN, Meads MB, Huang M, Jove R, Hazlehurst LA, Dalton WS. Beta1 integrin adhesion enhances IL-6-mediated STAT3 signaling in myeloma cells: implications for microenvironment influence on tumor survival and proliferation. Cancer Res. 2009 Feb;69(3):1009-1015. Pubmedid: 19155309. Pmcid: PMC2680075.
• Hazlehurst LA. Detection of DNA damage induced by topoisomerase II inhibitors, gamma radiation and crosslinking agents using the comet assay. Methods Mol Biol. 2009;523:169-176. Pubmedid: 19381939.
• Bewry NN, Nair RR, Emmons MF, Boulware D, Pinilla-Ibarz J, Hazlehurst LA. Stat3 contributes to resistance toward BCR-ABL inhibitors in a bone marrow microenvironment model of drug resistance. Mol Cancer Ther. 2008 Oct;7(10):3169-3175. Pubmedid: 18852120. Pmcid: PMC2676735.
• Koomen JM, Haura EB, Bepler G, Sutphen R, Remily-Wood ER, Benson K, Hussein M, Hazlehurst LA, Yeatman TJ, Hildreth LT, Sellers TA, Jacobsen PB, Fenstermacher DA, Dalton WS. Proteomic contributions to personalized cancer care. Mol Cell Proteomics. 2008 Oct;7(10):1780-1794. Pubmedid: 18664563. Pmcid: PMC2559938.
• Meads M, Hazlehurst L, Dalton W. The bone marrow microenvironment as a tumor sanctuary and contributor to drug resistance. Clin Cancer Res. 2008 May;14(9):2519-2526. Pubmedid: 18451212.
• Lwin T, Hazlehurst LA, Dessureault S, Lai R, Bai W, Sotomayor E, Moscinski LC, Dalton WS, Tao J. Cell adhesion induces p27Kip1-associated cell-cycle arrest through down-regulation of the SCFSkp2 ubiquitin ligase pathway in mantle-cell and other non-Hodgkin B-cell lymphomas. Blood. 2007 Sep;110(5):1631-1638. Pubmedid: 17502456. Pmcid: PMC1975846.
• Lwin T, Hazlehurst LA, Li Z, Dessureault S, Sotomayor E, Moscinski LC, Dalton WS, Tao J. Bone marrow stromal cells prevent apoptosis of lymphoma cells by upregulation of anti-apoptotic proteins associated with activation of NF-kappaB (RelB/p52) in non-Hodgkin's lymphoma cells. Leukemia. 2007 Jul;21(7):1521-1531. Pubmedid: 17476277.
• Hazlehurst LA, Argilagos RF, Dalton WS. Beta1 integrin mediated adhesion increases Bim protein degradation and contributes to drug resistance in leukaemia cells. Br J Haematol. 2007 Jan;136(2):269-275. Pubmedid: 17233818.
• Turner JG, Gump JL, Zhang C, Cook JM, Marchion D, Hazlehurst L, Munster P, Schell MJ, Dalton WS, Sullivan DM. ABCG2 expression, function, and promoter methylation in human multiple myeloma. Blood. 2006 Dec;108(12):3881-3889. Pubmedid: 16917002.
• Emmons M, Boulware D, Sullivan DM, Hazlehurst LA. Topoisomerase II beta levels are a determinant of melphalan-induced DNA crosslinks and sensitivity to cell death. Biochem Pharmacol. 2006 Jun;72(1):11-18. Pubmedid: 16678798.
• Hazlehurst L, Argilagos R, Emmons M, Boulware D, Beam C, Sullivan D, Dalton W. Cell adhesion to fibronectin (CAM-DR) influences acquired mitoxantrone resistance in U937 cells. Cancer Res. 2006 Feb;66(4):2338-2345. Pubmedid: 16489039.
• Chen Q, Van der Sluis P, Boulware D, Hazlehurst L, Dalton W. The FA/BRCA pathway is involved in melphalan-induced DNA interstrand cross-link repair and accounts for melphalan resistance in multiple myeloma cells. Blood. 2005 Jul;106(2):698-705. Pubmedid: 15802532.
• Dalton W, Hazlehurst L, Shain K, Landowski T, Alsina M. Targeting the bone marrow microenvironment in hematologic malignancies. Semin Hematol. 2004;41(2):1-5. Pubmedid: 15190509.
• Engel R, Valkov N, Gump J, Hazlehurst L, Dalton W, Sullivan D. The cytoplasmic trafficking of DNA topoisomerase IIalpha correlates with etoposide resistance in human myeloma cells. Exp Cell Res. 2004;295(2):421-431. Pubmedid: 15093741.
• Hazlehurst L, Enkemann S, Beam C, Argilagos R, Painter J, Shain K, Saporta S, Boulware L, Moscinski L, Alsina M, Dalton W. Genotypic and phenotypic comparisons of de-novo and acquired melphalan resistance in an isogenic multiple myeloma cell line model. Cancer Res. 2003;63(22):7900-7906. Pubmedid: 14633719.
• Hazlehurst L, Landowski T, Dalton W. Role of the tumor microenvironment in mediating de novo resistance to drugs and physiological mediators of cell death. Oncogene. 2003;22(47):7396-7402. Pubmedid: 14576847.
• Oshiro MM, Landowski TH, Catlett-Falcone R, Hazlehurst LA, Huang M, Jove R, Dalton WS. Inhibition of JAK kinase activity enhances Fas-mediated apoptosis but reduces cytotoxic activity of topoisomerase II inhibitors in U266 myeloma cells. Clin Cancer Res. 2001 Dec;7(12):4262-4271. Pubmedid: 11751528.
• Hazelhurst LA, Valkov N, Wisner L, Storey JA, Boulware D, Sullivan DM, Dalton WS. Reduction in drug-induced DNA double-strand breaks associated with beta1 integrin-mediated adhesion correlates with drug resistance in U937 cells. Blood. 2001 Sep;98(6):1897-1903. Pubmedid: 11535527.
• Damiano JS, Hazlehurst LA, Dalton WS. Cell adhesion-mediated drug resistance (CAM-DR) protects the K562 chronic myelogenous leukemia cell line from apoptosis induced by BCR/ABL inhibition, cytotoxic drugs, and gamma-irradiation. Leukemia. 2001 Aug;15(8):1232-1239. Pubmedid: 11480565.
• Hazlehurst L, Dalton W. Mechanisms associated with cell adhesion mediated drug resistance (CAM-DR) in hematopoietic malignancies. Cancer Metastasis Rev. 2001;20(1-2):43-50. Pubmedid: 11831646.
• Hazlehurst LA, Damiano JS, Buyuksal I, Pledger WJ, Dalton WS. Adhesion to fibronectin via beta1 integrins regulates p27kip1 levels and contributes to cell adhesion mediated drug resistance (CAM-DR). Oncogene. 2000 Sep;19(38):4319-4327. Pubmedid: 10980607.
• Anderson K, Kyle R, Dalton W, Landowski T, Shain K, Jove R, Hazlehurst L, Berenson J. Multiple Myeloma: New Insights and Therapeutic Approaches. Hematology (Am Soc Hematol Educ Program). 2000;147-165. Pubmedid: 11701540.
• Damiano J, Cress A, Hazlehurst L, Shtil A, Dalton W. Cell adhesion mediated drug resistance (CAM-DR): role of integrins and resistance to apoptosis in human myeloma cell lines. Blood. 1999;93(5):1658-1667. Pubmedid: 10029595.
• Hazlehurst L, Foley N, Gleason-Guzman M, Hacker M, Cress A, Greenberger L, De Jong M, Dalton W. Multiple mechanisms confer drug resistance to mitroxantrone in the human 8226 myeloma cell line. Cancer Res. 1999;59(5):1021-1028. Pubmedid: 10070958.
• Hazlehurst L, Gros P, Dalton W. Chromosome mediated gene tranfer of drug resistance to mitoxantrone. Anticancer Res. 1998;18:1005-1010. Pubmedid: 9615755.
• Hazlehurst L, Krapcho A, Hacker M. Comparison of aza-anthracenedione-induced DNA damage and cytotoxicity in experimental tumor cells. Biochem Pharmacol. 1995;50:1087-1094. Pubmedid: 7575665.
• Hazlehurst L, Krapcho A, Hacker M. Correlation of DNA reactivity and cytotoxicity of a new class of anticancer agents: aza-anthracenediones. Cancer Lett. 1995;91(1):115-124. Pubmedid: 7750086.