Beth Israel Deaconess Medical Center 330 Brookline Ave; HM-907
Boston, MA 02215
Advanced Degree And Training Info:
Year
Institution
Area or Rank
2000
FMRP - University of Sao Paulo - Brazil
MD
2001
Yale University School of Medicine
Intern Medicine
2002
Yale University School of Medicine
Resident Medicine
2004
Beth Israel Deaconess Medical Center - Harvard Medical School
Fellow Hem Oncology
2007
Beth Israel Deaconess Medical Center
Hem Oncology Staff
2007
Harvard Medical School
Instructor Med
2007
Harvard-MIT Division of Health Sciences and Technology
MMSc Fellow Clin Invest
Research Team Listing
No team members listed
Areas of Interest:
Cancer & Hematologic
Patient Oriented / Translational
Major Research Theme:
(co-investigators: Daniel G. Tenen, MD and Susumu Kobayashi, MD, PhD) Lung cancer is the leading cause of death from cancer in the United States. Better understanding of oncogenes and tumor suppressor genes involved in lung cancer hold the promise of improving clinical care of afflicted patients.
Our group is the lead site for Project 2 of the Lung SPORE at DFHCC. The transcription factors C/EBPalpha and Foxa2 play an essential role in airway epithelial differentiation, and are likely candidates in the pathogenesis of non-small cell lung cancer (NSCLC). Our group observed that many lung cancer cell lines have down-regulation of both C/EBPalpha and Foxa2 protein and mRNA, and hypothesized these transcription factors are novel tumor suppressor genes. We have started to correlate the immunohistochemical expression of C/EBPalpha and Foxa2 with pathological characteristics of primary lung tumors and the patients’ clinical outcomes. We also plan to identify the molecular mechanism of down-regulation of these genes, by studying if epigenetic or genetic changes are culprits. The last step of our project consists of testing compounds that can either re-establish C/EBPalpha-mediated pathways abrogated in NSCLC with special interest resides in the synthetic triterpenoids (CDDO and derivatives).
Another area of intense research by our laboratories is in the study of mechanisms of acquired resistance to gefitinib and erlotinib in EGFR-mutant NSCLCs and clinical response of patients with EGFR mutations to tyrosine kinase inhibitors (TKIs). Our group was one of the first to describe the T790M and L747S secondary resistant mutations. Current work will define a pharmacological response pattern of these T790M and non-T790M secondary mutations to established and novel EGFR inhibitors, with an aim of translating these findings into the clinic. We also have identified a key effector of TKI-induced apoptosis in the pro-apoptotic BH3-only peptide BIM. Efforts are underway on how to integrate these findings into clinical care of TKI-resistant patients.
I also am part of the clinical research effort at DFHCC, with a focus in non-small cell lung cancer. BIDMC is part of ongoing clinical trials at the DFHCC for EGFR mutated patients that progress after gefitinib and erlotinib (such as novel EGFR TKIs: DF-HCC 07-204 XL-647, 08-021 PF-00299804 among others; or MET TKIs: XL-184). Clinical trials are run in collaboration with Mark Huberman-BIDMC, Pasi Janne, Bruce Johnson, David Jackman-DFCI, Thomas Lynch, Jeffrey Engelman and Lecia Sequist-MGH).
Costa DB, Halmos B, Kumar A, Schumer ST, Huberman MS, Boggon TJ, Tenen DG, Kobayashi S. BIM mediates EGFR tyrosine kinase inhibitor-induced apoptosis in lung cancers with oncogenic EGFR mutations. PLoS Med 2007 Oct; 4(10):1669-1679; discussion 1680
Costa DB, Schumer ST, Tenen DG, Kobayashi S. Differential responses to erlotinib in EGFR mutated lung cancers with acquired resistance to gefitinib carrying the L747S or T790M secondary mutations. J Clin Oncol 2008; 26(7):1182-1184
Costa DB, Li S, Kocher O, Feins RH, Keller SM, Schiller JH, Johnson DH, Tenen DG, Halmos B. Immunohistochemical analysis of C/EBPalpha in non-small cell lung cancer reveals frequent down-regulation in stage II and IIIA tumors: A correlative study of E3590. Lung Cancer 2007 Apr; 56(1):97-103
Costa DB, Kobayashi S, Tenen DG, Huberman MS. Pooled analysis of the prospective trials of gefitinib monotherapy for EGFR-mutant non-small cell lung cancers. Lung Cancer 2007 Oct; 58(1):95-103
Costa DB, Dayaram T, D'Alo F, Wouters BJ, Tenen DG, Meyerson M, Tsao MS, Halmos B. C/EBPalpha mutations in lung cancer. Lung Cancer 2006 Aug; 53(2):253-254
External Recognition:
2007 Senior Research Training Fellowship – American Lung Association
2007 Young Investigator Award – American Society of Clinical Oncology (ASCO)
2007 Clinical Investigator Training Program – Beth Israel Deaconess Medical Center, Harvard Medical School/MIT
2007 AACR Fellowship in Translational Lung Cancer Research - American Association for Cancer Research (AACR)-AstraZeneca-Cancer Research and Prevention Foundation
Major Collaborative Activities:
Co-Leader - Lung Cancer SPORE DFHCC (2P50 CA090578-06, overall PI: Johnson DFCI): Project 2. “Foxa 2 and C/EBP transcription factors in the pathogenesis and treatment of lung cancer”
