Our research focuses on the molecular mechanisms that lead to oncogenesis and determine cancer risk and outcome. Currently, we are deciphering the molecular mechanisms by which secondhand smoke and electronic cigarette aerosols increase cancer risk. Our long term goals are to develop personalized preventive and therapeutic strategies. Our major areas of research are:
- DNA Damage and Repair: DNA damage is ultimately the main cause of cancer. Strikingly, chemo- and radio-therapy rely precisely on the induction of DNA damage to kill cancer cells. Hence, the inclusion of DNA damage parameters in cancer prediction models is anticipated to improve the accuracy of cancer risk and outcome estimation. Recently, we filled a major methodological gap in the field of DNA damage detection by developing a novel and highly sensitive assay (PADDA) to map and quantify in vivo DNA damage. PADDA has high sensitivity to detect DNA damage induced by diverse genotoxics including, UV light, tobacco smoke, and electronic cigarette aerosol. We are now exploring PADDA as a tool for the assessment of tobacco- and HPV-induced cancer risk.
- Cell Signaling and Stem Cells: We are using in vitro and in vivo models, as well as human patient samples, to study the mechanisms by which tobacco and electronic nicotine delivery systems interfere with stem cell regulation. We have shown that tobacco smoking selectively modifies the expression of specific Wnt pathway proteins leading to an increase in stem cells and resistance to chemotherapy. These studies have major clinical implications and might lead to the identification of novel prognostic markers and the development of new drugs targeting cancer stem cells.
Select Publications: (58% of peer-reviewed publications as first/last author)
- Muthusami S, Kumaran RI, Babu KN, Krishnamoorthy S, Guruswamy A, Queimado L, Chaudhuri G, and Ramachandran I. Role of inflammation in the development of colorectal cancer. Endocrine, Metabolic & Immune Disorders – Drug Targets . 2020 Sep 8; 20(1). doi: 10.2174/1871530320666200909092908. PMID: 32901590.
- Muthusami S, Ramachandran I, Krishnamoorthy S, Ramadoss S, Queimado L, Chaudhuri G, and Kumarans RI. Regulation of microRNAs in inflammation associated colorectal cancer: A Mechanistic Approach. Endocrine, Metabolic & Immune Disorders – Drug Targets . 2020 Sep17; 20(1). doi: 10.2174/1871530320666200917112802. PMID: 32940190.
- Floyd EL, Queimado L, Wang J, Regens JL, and Johnson DL. Electronic cigarette power affects count concentration and particle size distribution of vaping aerosol. PLoS One. 2018 Dec 31;13(12):e0210147. doi: 10.1371/journal.pone.0210147. eCollection 2018. PubMed PMID: 30596800.
- Queimado L, Wagener T, and Ganapathy V. Electronic cigarette aerosols induce DNA damage and reduce DNA repair: Consistency across species. Proc Natl Acad Sci USA. 2018 Jun 12;115(24):E5437-E5438. doi: 10.1073/pnas.1807411115. Epub 2018 May 25. PMCID: PMC6004470 (IF: 9.661).
- Ganapathy V, Manyanga J, Brame L, McGuire D, Sadhasivam B, Floyd E, Rubenstein DA, Ramachandran I, Wagener T, and Queimado L. Electronic cigarette aerosols suppress cellular antioxidant defenses and induce significant oxidative DNA damage. PLoS One. 2017, May 18;12(5):e0177780. doi: 10.1371/journal.pone.0177780. PMCID: PMC5436899 (IF: 3.54).
- Wagener TL, Floyd EL, Stepanov I, Driskill LM, Frank SG, Meier E, Leavens EL, Tackett AP, Molina N, and Queimado L. Have combustible cigarettes met their match? The nicotine delivery profiles and harmful constituent exposures of second- and third-generation electronic cigarette users. Tob Control, Online First. Oct 11, 2016; doi:10.1136/tobaccocontrol-2016-053041. PMID: 27729564 (IF: 5.933).
- Drier Y, Cotton MJ, Williamson KE, Gillespie SM, Ryan RJ, Kluk MJ, Carey CD, Rodig SJ, Sholl LM, Afrogheh AH, Faquin WC, Queimado L, Qi J, Wick MJ, El-Naggar AK, Bradner JE, Moskaluk CA, Aster JC, Knoechel B, and Bernstein BE. An oncogenic MYB feedback loop drives alternate cell fates in adenoid cystic carcinoma. Nat Genet. 2016 Feb 1; doi: 10.1038/ng.3502. (IF: 29.352).
- Ganapathy V, Ramachandran I, Rubenstein D, and Queimado L. Detection of in vivo DNA damage induced by very low doses of mainstream and sidestream smoke extracts using a novel assay. J Okla State Med Assoc. 2015 Nov;108(11):500-508. Re-printed (Tobacco Use Prevention and Cessation Issue).
- Ganapathy V, Ramachandran I, Rubenstein D, and Queimado L. Detection of in vivo DNA damage induced by very low doses of mainstream and sidestream smoke extracts using a novel assay. Amer J Prev Med. 2015; 48 (1 Suppl 1):S102-110, 2015. (IF: 4.281). Manuscript recognized as a landmark study by Action to Quit (April, 2015).
- Ramachandran I, Ganapathy V, Gillies E, Fonseca I, Sureban SM, Houchen CW, Reis A, and Queimado L. Wnt inhibitory factor 1 suppresses cancer stemness and induces cellular senescence. Cell Death Dis. 2014; 22(5):e1246, doi: 10.1038/cddis.2014.219. PMID: 24853424. (IF: 5.177).
- Warner KA, Adams A, Bernardi L, Nor C, Finkel KA, Zhang Z, McLean SA, Helman J, Wolf GT, Divi V, Queimado L, Kaye FJ, Castilho R, and Nör JE. Characterization of tumorigenic cell lines from the recurrence and lymph node metastasis of a human salivary mucoepidermoid carcinoma. Oral Oncology. 2013; 49(11):1059-1066. (IF: 3.029).
- Allred C, Queimado L, and Krempl G. Postintubation tracheal stenosis: Case report and guide to management. J Case Reports Medicine. 2013; 2, doi:10.4303/jcrm/235633.
- Moxley KM, Benbrook DM, Queimado L, Zuna RE, Thompson D, McCumber M, Premkumar P, Thavathiru E, Hines L, and Moore KN. The role of single nucleotide polymorphisms of the ERCC1 and MMS19 genes in predicting platinum-sensitivity, progression-free and overall survival in advanced epithelial ovarian cancer. Gynecol Oncol. 2013; 130(2):377-382. (IF: 3.687).