Photo of Elena Levantini,  PhD

Elena Levantini, PhD

Beth Israel Deaconess Medical Center

Beth Israel Deaconess Medical Center
Phone: (617) 735-2233
Fax: (617) 735-2222

Elena Levantini, PhD

Beth Israel Deaconess Medical Center


  • Instructor, Medicine, Harvard Medical School
  • Research Associate, Hematology-Oncology, Beth Israel Deaconess Medical Center


Research Abstract

Lung cancer is the principal cause of cancer mortality in the world, and its frequency is increasing. Hence, improved therapeutic options are imperative. There is a strong correlation between tobacco exposure and lung carcinogenesis, and the best protection against lung cancer is the avoidance of smoking. Advances in lung cancer therapy require a greater understanding of the molecular pathogenesis of this disease. Previously, we showed that the leucine zipper family transcription factor CCAAT/enhancer binding protein alpha (C/EBPα), a proposed tumor suppressor in acute myeloid leukemia (AML), is down-regulated in non-small cell lung cancer. Furthermore, ectopic expression of C/EBPα in the lung cancer cell lines led to significant growth reduction attributable to proliferation arrest, morphological changes characteristic of differentiation, and apoptosis. Additionally, mice with specific conditional loss of C/EBPα in the lung showed symptoms of respiratory distress accompanied by perinatal death, therefore hinting to potential therapeutical benefits that might be obtained by exploring the C/EBPα pathway in patients with respiratory distress syndrome. Based on these observations, we are exploring the effects of C/EBPα down-regulation in experimental models of lung cancer and tobacco-damaged epithelium, using our inducible models of lung-specific C/EBPα deletion. We are also analyzing the differentiation and self-renewal capabilities of C/EBPα-deleted pulmonary stem cells, in order to gain knowledge on the molecular mechanisms that C/EBPα is orchestrating in lung stem cells.

Characterization of critical regulatory mechanisms governed by the master regulator C/EBPα as well as the aberrant differentiation pathways in C/EBPα-deleted pulmonary stem cells would be of critical relevance for our better understanding the pathogenesis of as well as the identification of novel treatment targets for tobacco-related lung diseases, such as lung cancer and emphysema.

Publications from Harvard Catalyst Profiles

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  • Maroni G, Bassal MA, Krishnan I, Fhu CW, Savova V, Zilionis R, Maymi VA, Pandell N, Csizmadia E, Zhang J, Storti B, Castaño J, Panella R, Li J, Gustafson CE, Fox S, Levy RD, Meyerovitz CV, Tramontozzi PJ, Vermilya K, De Rienzo A, Crucitta S, Bassères DS, Weetall M, Branstrom A, Giorgetti A, Ciampi R, Del Re M, Danesi R, Bizzarri R, Yang H, Kocher O, Klein AM, Welner RS, Bueno R, Magli MC, Clohessy JG, Ali A, Tenen DG, Levantini E. Identification of a targetable KRAS-mutant epithelial population in non-small cell lung cancer. Commun Biol 2021; 4:370. PubMed
  • Trinh BQ, Ummarino S, Zhang Y, Ebralidze AK, Bassal MA, Nguyen TM, Heller G, Coffey R, Tenen DE, van der Kouwe E, Fabiani E, Gurnari C, Wu CS, Espinosa Angarica V, Yang H, Chen S, Zhang H, Thurm AR, Marchi F, Levantini E, Staber PB, Zhang P, Voso MT, Pandolfi PP, Kobayashi SS, Chai L, Di Ruscio A, Tenen DG. Myeloid lncRNA LOUP Mediates Opposing Regulatory Effects of RUNX1 and RUNX1-ETO in t(8;21) AML. Blood 2021. PubMed
  • Rodrigues FS, Miranda VS, Carneiro-Lobo TC, Scalabrini LC, Kruspig B, Levantini E, Murphy DJ, Bassères DS. IKKβ Kinase Promotes Stemness, Migration, and Invasion in KRAS-Driven Lung Adenocarcinoma Cells. Int J Mol Sci 2020. PubMed
  • Gomes-Filho SM, Dos Santos EO, Bertoldi ERM, Scalabrini LC, Heidrich V, Dazzani B, Levantini E, Reis EM, Bassères DS. Aurora A kinase and its activator TPX2 are potential therapeutic targets in KRAS-induced pancreatic cancer. Cell Oncol (Dordr) 2020. PubMed
  • Chin TM, Boopathy GTK, Man EPS, Clohessy JG, Csizmadia E, Quinlan MP, Putti T, Wan SC, Xie C, Ali A, Wai FC, Ong YS, Goh BC, Settleman J, Hong W, Levantini E, Tenen DG. Targeting microtubules sensitizes drug resistant lung cancer cells to lysosomal pathway inhibitors. Theranostics 2020; 10:2727-2743. PubMed
  • Storti B, Civita S, Faraci P, Maroni G, Krishnan I, Levantini E, Bizzarri R. Fluorescence imaging of biochemical relationship between ubiquitinated histone 2A and Polycomb complex protein BMI1. Biophys. Chem. 2019; 253:106225. PubMed
  • Maroni G, Panetta D, Luongo R, Krishnan I, La Rosa F, Campani D, Salvadori P, Iozzo P, Blasi F, Penkov D, Levantini E, Magli MC. The Role of Prep1 in the Regulation of Mesenchymal Stromal Cells. Int J Mol Sci 2019. PubMed
  • Zilionis R, Engblom C, Pfirschke C, Savova V, Zemmour D, Saatcioglu HD, Krishnan I, Maroni G, Meyerovitz CV, Kerwin CM, Choi S, Richards WG, De Rienzo A, Tenen DG, Bueno R, Levantini E, Pittet MJ, Klein AM. Single-Cell Transcriptomics of Human and Mouse Lung Cancers Reveals Conserved Myeloid Populations across Individuals and Species. Immunity 2019; 50:1317-1334.e10. PubMed
  • Carneiro-Lobo TC, Scalabrini LC, Magalhães LDS, Cardeal LB, Rodrigues FS, Dos Santos EO, Baldwin AS, Levantini E, Giordano RJ, Bassères DS. IKKβ targeting reduces KRAS-induced lung cancer angiogenesis in vitro and in vivo: A potential anti-angiogenic therapeutic target. Lung Cancer 2019; 130:169-178. PubMed
  • Ali A, Levantini E, Fhu CW, Teo JT, Clohessy JG, Goggi JL, Wu CS, Chen L, Chin TM, Tenen DG. CAV1 - GLUT3 signaling is important for cellular energy and can be targeted by Atorvastatin in Non-Small Cell Lung Cancer. Theranostics 2019; 9:6157-6174. PubMed
  • Ali A, Levantini E, Teo JT, Goggi J, Clohessy JG, Wu CS, Chen L, Yang H, Krishnan I, Kocher O, Zhang J, Soo RA, Bhakoo K, Chin TM, Tenen DG. Fatty acid synthase mediates EGFR palmitoylation in EGFR mutated non-small cell lung cancer. EMBO Mol Med 2018. PubMed
  • Maroni G, Tkachuk VA, Egorov A, Morelli MJ, Luongo R, Levantini E, Blasi F, Magli MC, Penkov D. Prep1 prevents premature adipogenesis of mesenchymal progenitors. Sci Rep 2017; 7:15573. PubMed
  • Gonzalez D, Luyten A, Bartholdy B, Zhou Q, Kardosova M, Ebralidze A, Swanson KD, Radomska H, Zhang P, Kobayashi SS, Welner RS, Levantini E, Steidl U, Chong G, Collombet S, Choi MH, Friedman AD, Scott LM, Alberich-Jorda M, Tenen DG. ZNF143 is an important regulator of the myeloid transcription factor C/EBPα. J Biol Chem 2017. PubMed
  • Patnaik A, Swanson KD, Csizmadia E, Solanki A, Landon-Brace N, Gehring MP, Helenius K, Olson BM, Pyzer AR, Wang LC, Elemento O, Novak J, Thornley TB, Asara JM, Montaser L, Timmons JJ, Morgan TM, Wang Y, Levantini E, Clohessy JG, Kelly K, Pandolfi PP, Rosenblatt JM, Avigan DE, Ye H, Karp JM, Signoretti S, Balk SP, Cantley LC. Cabozantinib Eradicates Advanced Murine Prostate Cancer by Activating Anti-Tumor Innate Immunity. 2017. PubMed
  • Bonifer C, Levantini E, Kouskoff V, Lacaud G. Runx1 Structure and Function in Blood Cell Development. Adv Exp Med Biol 2017; 962:65-81. PubMed
  • Yong KJ, Basseres DS, Welner RS, Zhang WC, Yang H, Yan B, Alberich-Jorda M, Zhang J, de Figueiredo-Pontes LL, Battelli C, Hetherington CJ, Ye M, Zhang H, Maroni G, O'Brien K, Magli MC, Borczuk AC, Varticovski L, Kocher O, Zhang P, Moon YC, Sydorenko N, Cao L, Davis TW, Thakkar BM, Soo RA, Iwama A, Lim B, Halmos B, Neuberg D, Tenen DG, Levantini E. Targeted BMI1 inhibition impairs tumor growth in lung adenocarcinomas with low CEBPα expression. Sci Transl Med 2016; 8:350ra104. PubMed
  • Dos Santos EO, Carneiro-Lobo TC, Aoki MN, Levantini E, Bassères DS. Aurora kinase targeting in lung cancer reduces KRAS-induced transformation. Mol Cancer 2016; 15:12. PubMed
  • Bararia D, Kwok HS, Welner RS, Numata A, Sárosi MB, Yang H, Wee S, Tschuri S, Ray D, Weigert O, Levantini E, Ebralidze AK, Gunaratne J, Tenen DG. Acetylation of C/EBPα inhibits its granulopoietic function. Nat Commun 2016; 7:10968. PubMed
  • Ye M, Zhang H, Yang H, Koche R, Staber PB, Cusan M, Levantini E, Welner RS, Bach CS, Zhang J, Krivtsov AV, Armstrong SA, Tenen DG. Hematopoietic Differentiation Is Required for Initiation of Acute Myeloid Leukemia. Cell Stem Cell 2015. PubMed
  • Welner RS, Amabile G, Bararia D, Czibere A, Yang H, Zhang H, Pontes LL, Ye M, Levantini E, Di Ruscio A, Martinelli G, Tenen DG. Treatment of chronic myelogenous leukemia by blocking cytokine alterations found in normal stem and progenitor cells. Cancer Cell 2015; 27:671-81. PubMed
  • Cai Y, Hirata A, Nakayama S, VanderLaan PA, Levantini E, Yamamoto M, Hirai H, Wong KK, Costa DB, Watanabe H, Kobayashi SS. CCAAT/enhancer binding protein β is dispensable for development of lung adenocarcinoma. PLoS ONE 2015; 10:e0120647. PubMed
  • Amabile G, Di Ruscio A, Müller F, Welner RS, Yang H, Ebralidze AK, Zhang H, Levantini E, Qi L, Martinelli G, Brummelkamp T, Le Beau MM, Figueroa ME, Bock C, Tenen DG. Dissecting the role of aberrant DNA methylation in human leukaemia. Nat Commun 2015; 6:7091. PubMed
  • Staber PB, Zhang P, Ye M, Welner RS, Levantini E, Di Ruscio A, Ebralidze AK, Bach C, Zhang H, Zhang J, Vanura K, Delwel R, Yang H, Huang G, Tenen DG. The Runx-PU.1 pathway preserves normal and AML/ETO9a leukemic stem cells. Blood 2014; 124:2391-9. PubMed
  • Zhang H, Alberich-Jorda M, Amabile G, Yang H, Staber PB, Di Ruscio A, Diruscio A, Welner RS, Ebralidze A, Zhang J, Levantini E, Lefebvre V, Valk PJ, Delwel R, Hoogenkamp M, Nerlov C, Cammenga J, Saez B, Scadden DT, Bonifer C, Ye M, Tenen DG. Sox4 is a key oncogenic target in C/EBPα mutant acute myeloid leukemia. Cancer Cell 2013; 24:575-88. PubMed
  • Ye M, Zhang H, Amabile G, Yang H, Staber PB, Zhang P, Levantini E, Alberich-Jordà M, Zhang J, Kawasaki A, Tenen DG. C/EBPa controls acquisition and maintenance of adult haematopoietic stem cell quiescence. Nat Cell Biol 2013; 15:385-94. PubMed
  • O'Brien KB, Alberich-Jordà M, Yadav N, Kocher O, Diruscio A, Ebralidze A, Levantini E, Sng NJ, Bhasin M, Caron T, Kim D, Steidl U, Huang G, Halmos B, Rodig SJ, Bedford MT, Tenen DG, Kobayashi S. CARM1 is required for proper control of proliferation and differentiation of pulmonary epithelial cells. Development 2010; 137:2147-56. PubMed
  • Bassères DS, Ebbs A, Levantini E, Baldwin AS. Requirement of the NF-kappaB subunit p65/RelA for K-Ras-induced lung tumorigenesis. Cancer Res 2010; 70:3537-46. PubMed
  • Guibal FC, Alberich-Jorda M, Hirai H, Ebralidze A, Levantini E, Di Ruscio A, Zhang P, Santana-Lemos BA, Neuberg D, Wagers AJ, Rego EM, Tenen DG. Identification of a myeloid committed progenitor as the cancer-initiating cell in acute promyelocytic leukemia. Blood 2009; 114:5415-25. PubMed
  • Peter Y,Comellas A,Levantini E,Ingenito EP,Shapiro SD. Epidermal growth factor receptor and claudin-2 participate in A549 permeability and remodeling: implications for non-small cell lung cancer tumor colonization. Mol Carcinog 2009; 48:488-97. PubMed
  • Koschmieder S,Halmos B,Levantini E,Tenen DG. Dysregulation of the C/EBPalpha differentiation pathway in human cancer. J Clin Oncol 2009; 27:619-28. PubMed
  • Koschmieder S, D'Alo F, Radomska H, Schoneich C, Chang JS, Konopleva M, Kobayashi S, Levantini E, Suh N, Di Ruscio A, Voso MT, Watt JC, Santhanam R, Sargin B, Kantarjian H, Andreeff M, Sporn MB, Perrotti D, Berdel WE, Muller-Tidow C, Serve H, Tenen DG. CDDO induces granulocytic differentiation of myeloid leukemic blasts through translational up-regulation of p42 CCAAT enhancer binding protein alpha. Blood 2007; 110:3695-705. PubMed
  • Kubo S, Levantini E, Kobayashi S, Kocher O, Halmos B, Tenen DG, Takahashi M. Three-dimensional magnetic resonance microscopy of pulmonary solitary tumors in transgenic mice. Magn Reson Med 2006; 56:698-703. PubMed
  • Bassères DS, Levantini E, Ji H, Monti S, Elf S, Dayaram T, Fenyus M, Kocher O, Golub T, Wong KK, Halmos B, Tenen DG. Respiratory failure due to differentiation arrest and expansion of alveolar cells following lung-specific loss of the transcription factor C/EBPalpha in mice. Mol Cell Biol 2006; 26:1109-23. PubMed