Dr. Seyed Javad M. Moghaddam
The University of Texas MD Anderson Cancer Center
Department of Pulmonary Medicine
- Role of airway inflammation in lung carcinogenesis
The research in my lab focuses on airway inflammation and its role in airway epithelial carcinogenesis. Cigarette smoking is the principal cause of lung carcinogenesis. However, more than ten separate studies have found that smokers with chronic obstructive pulmonary disease (COPD), an inflammatory disease of the airways and alveoli, have an increased risk of lung cancer compared to smokers with comparable cigarette exposure but without COPD. This suggests a strong link between COPD-related airway inflammation and lung cancer. We have previously shown that COPD-like airway inflammation, but not asthma-like airway inflammation, promotes lung cancer in a K-ras mutant mouse model. We are currently dissecting the mechanism responsible for this phenomenon. To study these, we have generated/obtained knockout mice for each pathway, and cells, and we have also developed techniques to transgenically overexpress them.
This will provide a better understanding of the role of specific inflammatory pathways in lung carcinogenesis, and subsequently allow preclinical testing of the efficacy of anti-inflammatory agents in preventing lung cancer. This would have a major impact on preventing the leading cause of cancer death by providing the basis for rationally directed therapy in patients at high risk for lung cancer development, and patients with early stage tumors.
Students working in my laboratory will have the opportunity to study lung biology, airway inflammation, molecular aspects of lung cancer, and tumor microenvironment. Techniques include microscopic analysis, immunohistochemistry, molecular cloning, and transgenic modeling.
Moghaddam SJ, Clement CG, De la Garza MM, Zou X, Travis EL, Young HW, Evans CM, Tuvim MJ, Dickey BF. Haemophilus influenzae Lysate Induces Aspects of the Chronic Obstructive Pulmonary Disease Phenotype. Am J Respir Cell Mol Biol 38(6):629-38 (Cover), 6/2008. e-Pub 12/2007. PMCID: PMC2396243.
Moghaddam SJ, Li H, Cho SN, Dishop MK, Wistuba II, Ji L, Kurie JM, Dickey BF, Demayo FJ. Promotion of Lung Carcinogenesis by COPD-Like Airway Inflammation in a K ras Induced Mouse Model. Am J Respir Cell Mol Biol 40(4):443-53 (Cover Art), 4/2009. e-Pub 10/2008. PMCID: PMC2660561.
Moghaddam SJ, Barta P, Mirabolfathinejad SG, Ammar-Aouchiche Z, Garza NT, Vo TT, Newman RA, Aggarwal BB, Evans CM, Tuvim MJ, Lotan R, Dickey BF. Curcumin Inhibits COPD-Like Airway Inflammation and Lung Cancer Progression in Mice. Carcinogenesis. Carcinogenesis 30(11):1949-56, 11/2009. e-Pub 9/2009. PMCID: PMC2783007.
Ochoa CE, Mirabolfathinejad SG, Ruiz VA, Evans SE, Gagea M, Evans CM, Dickey BF, Moghaddam SJ. Interleukin 6 But Not T helper 2 Cytokines Promotes Lung Carcinogenesis. Cancer Prev Res (Phila). 2011 Jan;4(1):51-64. (PMID: 21098042) (PMCID: PMC3058282).
Barta P, Van Pelt C, Men T, Dickey BF, Lotan R, Moghaddam SJ. Enhancement of Lung Tumorigenesis in a Gprc5a Knockout Mouse by Chronic Extrinsic Airway Inflammation. Mol Cancer. 2012 Jan 12;11(1):4. (PMID: 22239913) (PMCID: PMC3281775).