Lia E. Perez, MD

The research efforts of Dr. Perez’s group have concentrated on understanding how the tumor microenvironment regulates immune-mediated apoptosis of cancer cells. They investigated whether tumor microenvironment induces resistance to APO2L/TRAIL apoptosis in multiple myeloma. The hypothesis is that bone marrow stroma provides a sanctuary where tumor can resist APO2L/TRAIL mediated killing by evading in vivo homeostatic tumor surveillance mechanisms. Data generated has led to publications describing the role of stroma:myeloma cytokine network on TRAIL mediated killing, establishing a novel concept on immune resistance: Environmental Mediated-Immune Resistance (EM-IR).  Extensive mechanistic work has elucidated that the anti-apoptotic protein c-FLIP plays a pivotal role in immune resistance.  They tested the hypothesis that proteosome inhibition or HDAC inhibitors may reverse APO2L/TRAIL EM-IR through its effects on APO2L/TRAIL signaling pathways and/or related to modifications of stroma induced signals. They discovered that pretreatment with bortezomib effectively overcomes APO2L/TRAIL apoptosis resistance. The findings provide the rationale to combine therapeutics agents to disrupt the influence of the stroma microenvironment on myeloma cells.

• Kharfan-Dabaja MA, Anasetti C, Fernandez HF, Perkins J, Ochoa-Bayona JL, Pidala J, Perez LE, Ayala E, Field T, Alsina M, Nishihori T, Locke F, Pinilla-Ibarz J, Tomblyn M. Phase II study of CD4+guided pentostatin lymphodepletion and pharmacokinetically-targeted busulfan as conditioning for hematopoietic cell allografting. Biol Blood Marrow Transplant. 2013 Apr. Pubmedid: 23632090.
• Pidala J, Kim J, Schell M, Lee SJ, Hillgruber R, Nye V, Ayala E, Alsina M, Betts B, Bookout R, Fernandez HF, Field T, Locke FL, Nishihori T, Ochoa JL, Perez L, Perkins J, Shapiro J, Tate C, Tomblyn M, Anasetti C. Race/ethnicity affects the probability of finding an HLA-A, -B, -C and -DRB1 allele-matched unrelated donor and likelihood of subsequent transplant utilization. Bone Marrow Transplant. 2013 Mar;48(3):346-350. Pubmedid: 22863723.
• Pidala J, Kim J, Jim H, Kharfan-Dabaja MA, Nishihori T, Fernandez HF, Tomblyn M, Perez L, Perkins J, Xu M, Janssen WE, Veerapathran A, Betts BC, Locke FL, Ayala E, Field T, Ochoa L, Alsina M, Anasetti C. A randomized phase II study to evaluate tacrolimus in combination with sirolimus or methotrexate after allogeneic hematopoietic cell transplantation. Haematologica. 2012 Dec;97(12):1882-1889. Pubmedid: 22689677.
• Boucher K, Parquet N, Widen R, Shain K, Baz R, Alsina M, Koomen J, Anasetti C, Dalton W, Perez LE. Stemness of B-cell Progenitors in Multiple Myeloma Bone Marrow. Clin Cancer Res. 2012 Nov;18(22):6155-6168. Pubmedid: 22988056.
• Perkins JB, Kim J, Anasetti C, Fernandez HF, Perez LE, Ayala E, Kharfan-Dabaja MA, Tomblyn MR, Sullivan DM, Pidala JA, Field TL. Maximally Tolerated Busulfan Systemic Exposure in Combination with Fludarabine as Conditioning before Allogeneic Hematopoietic Cell Transplantation. Biol Blood Marrow Transplant. 2012 Jul;18(7):1099-1107. Pubmedid: 22198540.
• Nishihori T, Alekshun TJ, Shain K, Sullivan DM, Baz R, Perez L, Pidala J, Kharfan-Dabaja MA, Ochoa-Bayona JL, Fernandez HF, Yarde DN, Oliveira V, Fulp W, Han G, Kim J, Chen DT, Raychaudhuri J, Dalton W, Anasetti C, Alsina M. Bortezomib salvage followed by a Phase I/II study of bortezomib plus high-dose melphalan and tandem autologous transplantation for patients with primary resistant myeloma. Br J Haematol. 2012 Jun;157(5):553-563. Pubmedid: 22449149.
• Liu JJ, Zhang L, Ayala E, Field T, Ochoa-Bayona JL, Perez L, Bello CM, Chervenick PA, Bruno S, Cultrera JL, Baz RC, Kharfan-Dabaja MA, Raychaudhuri J, Sotomayor EM, Sokol L. Human immunodeficiency virus (HIV)-negative plasmablastic lymphoma: a single institutional experience and literature review. Leuk Res. 2011 Dec;35(12):1571-1577. Pubmedid: 21752466.
• Perkins J, Field T, Kim J, Kharfan-Dabaja MA, Ayala E, Perez L, Fernandez H, Fancher K, Tate C, Shaw LM, Milone MC, Gardiner JA, Miller S, Anasetti C. Pharmacokinetic targeting of i.v. BU with fludarabine as conditioning before hematopoietic cell transplant: the effect of first-dose area under the concentration time curve on transplant-related outcomes. Bone Marrow Transplant. 2011 Nov;46(11):1418-1425. Pubmedid: 21132026.
• 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.
• Perez L, Anasetti C, Pidala J. Have we improved in preventing and treating acute graft-versus-host disease?. Curr Opin Hematol. 2011 Nov;18(6):408-413. Pubmedid: 21912253. Pmcid: PMC3432261.
• Perez LE. Outcomes from unrelated donor hematopoietic stem cell transplantation. Cancer Control. 2011 Oct;18(4):216-221. Pubmedid: 21976240.
• Santarone S, Pidala J, Di Nicola M, Field T, Alsina M, Ayala E, Janssen W, Kharfan-Dabaja MA, Ochoa L, Perez L, Perkins J, Raychaudhuri J, Fernandez H, Anasetti C. Fludarabine and pharmacokinetic-targeted busulfan before allografting for adults with acute lymphoid leukemia. Biol Blood Marrow Transplant. 2011 Oct;17(10):1505-1511. Pubmedid: 21385623.
• Pidala J, Tomblyn M, Nishihori T, Field T, Ayala E, Perkins J, Fernandez H, Locke F, Perez L, Ochoa JL, Alsina M, Anasetti C. Sirolimus demonstrates activity in the primary therapy of acute graft-versus-host disease without systemic glucocorticoids. Haematologica. 2011 Sep;96(9):1351-1356. Pubmedid: 21565902. Pmcid: PMC3166106.
• Pidala J, Tomblyn M, Nishihori T, Ayala E, Field T, Fernandez H, Perez L, Locke F, Alsina M, Ochoa JL, Perkins J, Tate C, Shapiro J, Conwell M, Bookout R, Anasetti C. ATG Prevents Severe Acute Graft-versus-Host Disease in Mismatched Unrelated Donor Hematopoietic Cell Transplantation. Biol Blood Marrow Transplant. 2011 Aug;17(8):1237-1244. Pubmedid: 21215811.
• Pidala J, Kim J, Anasetti C, Kharfan-Dabaja MA, Field T, Perkins J, Ayala E, Perez L, Fernandez H. Targeted i.v. BU and fludarabine (t-i.v. BU/Flu) provides effective control of AML in adults with reduced toxicity. Bone Marrow Transplant. 2011 May;46(5):641-649. Pubmedid: 20711242.
• Kharfan-Dabaja MA, Chavez JC, Yu D, Zhu W, Fernandez-Vertiz EI, Perkins J, Shapiro J, Bookout R, Perez L, Fernandez HF, Komrokji RS, Lancetf J, Brand L, Field T, Ayala E, Janssen W, List AF, Anasetti C. Severe hypoalbuminemia at day 90 predicts worse nonrelapse mortality and overall survival after allogeneic hematopoietic stem cell transplantation for acute myelogenous leukemia and myelodysplastic syndrome. Biol Blood Marrow Transplant. 2011 Mar;17(3):384-393. Pubmedid: 20655389.
• Pidala J, Kim J, Kharfan-Dabaja MA, Nishihori T, Field T, Perkins J, Perez L, Fernandez H, Anasetti C. Dysglycemia Following Glucocorticoid Therapy for Acute Graft-versus-Host Disease Adversely Affects Transplantation Outcomes. Biol Blood Marrow Transplant. 2011 Feb;17(2):239-248. Pubmedid: 20637884.
• Hoda D, Pidala J, Salgado-Vila N, Kim J, Perkins J, Bookout R, Field T, Perez L, Ayala E, Ochoa-Bayona JL, Raychaudhuri J, Alsina M, Greene J, Janssen W, Fernandez HF, Anasetti C, Kharfan-Dabaja MA. Sirolimus for treatment of steroid-refractory acute graft-versus-host disease. Bone Marrow Transplant. 2010 Aug;45(8):1347-1351. Pubmedid: 19966849.
• Lu SX, Holland AM, Na IK, Terwey TH, Alpdogan O, Bautista JL, Smith OM, Suh D, King C, Kochman A, Hubbard VM, Rao UK, Yim N, Liu C, Laga AC, Murphy G, Jenq RR, Zakrzewski JL, Penack O, Dykstra L, Bampoe K, Perez L, Furie B, Furie B, van den Brink MR. Absence of P-selectin in recipients of allogeneic bone marrow transplantation ameliorates experimental graft-versus-host disease. J Immunol. 2010 Aug;185(3):1912-1919. Pubmedid: 20622117.
• Perkins J, Field T, Kim J, Kharfan-Dabaja MA, Fernandez H, Ayala E, Perez L, Xu M, Alsina M, Ochoa L, Sullivan D, Janssen W, Anasetti C. A Randomized Phase II Trial Comparing Tacrolimus and Mycophenolate Mofetil to Tacrolimus and Methotrexate for Acute Graft-versus-Host Disease Prophylaxis. Biol Blood Marrow Transplant. 2010 Jul;16(7):937-947. Pubmedid: 20102746.
• Pidala J, Kim J, Perkins J, Field T, Fernandez H, Perez L, Ayala E, Kharfan-Dabaja M, Anasetti C. Mycophenolate mofetil for the management of steroid-refractory acute graft vs host disease. Bone Marrow Transplant. 2010 May;45(5):919-924. Pubmedid: 19767783.
• Perez LE, Parquet N, Meads M, Anasetti C, Dalton W. Bortezomib restores stroma-mediated APO2L/TRAIL apoptosis resistance in multiple myeloma. Eur J Haematol. 2010 Mar;84(3):212-222. Pubmedid: 19922463.
• Field T, Perkins J, Huang Y, Kharfan-Dabaja MA, Alsina M, Ayala E, Fernandez HF, Janssen W, Lancet J, Perez L, Sullivan D, List A, Anasetti C. 5-Azacitidine for myelodysplasia before allogeneic hematopoietic cell transplantation. Bone Marrow Transplant. 2010 Feb;45(2):255-260. Pubmedid: 19543327.
• Pidala J, Kim J, Anasetti C, Kharfan-Dabaja MA, Nishihori T, Field T, Perkins J, Perez L, Fernandez HF. Pharmacokinetic targeting of intravenous busulfan reduces conditioning regimen related toxicity following allogeneic hematopoietic cell transplantation for acute myelogenous leukemia. J Hematol Oncol. 2010;3:36. Pubmedid: 20925957. Pmcid: PMC2958877.
• Pidala J, Kim J, Field T, McBride A, Kharfan-Dabaja M, Perkins J, Fernandez H, Perez L, Ayala E, Anasetti C. Infliximab for managing steroid-refractory acute graft-versus-host disease. Biol Blood Marrow Transplant. 2009 Sep;15(9):1116-1121. Pubmedid: 19660725.
• Perez L, Parquet N, Shain K, Nimmanapalli R, Alsina M, Anasetti C, Dalton W. Bone Marrow Stroma Confers Resistance to Apo2 Ligand/TRAIL in Multiple Myeloma inPart by Regulating c-FLIP. J Immunol. 2008 Feb;180(3):1545-1555. Pubmedid: 18209050.
• Perez LE, Desponts C, Parquet N, Kerr WG. SH2-inositol phosphatase 1 negatively influences early megakaryocyte progenitors. PLoS One. 2008;3(10):e3565-e3565. Pubmedid: 18958162.
• Yanamandra N, Colaco N, Parquet N, Buzzeo R, Boulware D, Wright G, Perez LE, Dalton W, Beaupre D. Tipifarnib and bortezomib are synergistic and overcome cell adhesion-mediated drug resistance in multiple myeloma and acute myeloid leukemia. Clin Cancer Res. 2006 Jan;12(2):591-599. Pubmedid: 16428505.
• Perez L, Alpdogan O, Shieh J, Wong D, Merzouk A, Salari H, Oreilley R, van den Brink M, Moore M. Increased plasma levels of stromal-derived factor-1 (SDF-1/CXCL12) enhance human thrombopoiesis and mobilize human colony forming cells (CFC) in NOD/SCID mice. Exp Hematol. 2004;32(3):300-307. Pubmedid: 15003316.
• Anstead GM, Chandrasekar B, Zhao W, Yang J, Perez LE, Melby PC. Malnutrition alters the innate immune response and increases early visceralization following Leishmania donovani infection. Infect Immun. 2001 Aug;69(8):4709-4718. Pubmedid: 11447142. Pmcid: PMC98556.
• Rathbun ED, Perez LE, Barry RE. Prenatal laboratory screening. Tex Med. 1990 Mar;86(3):52-57. Pubmedid: 2185578.