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.


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  • 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
  • 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
  • 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 硫 Is Dispensable for Development of Lung Adenocarcinoma. PLoS ONE 2015; 10:e0120647. 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/EBP留 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 2008; 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 2008; 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
  • Bass. 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