https://medicine.ouhsc.edu/Academic-Departments Parent Page: Academic Departments id: 22035 Active Page: Research Interestsid:22039

Research Interests

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:

  1. 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.
  2. 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)

  1. 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. Endocr Metab Immune Disord Drug Targets. 2021 Jan 26; 21(1):77-90. doi: 10.2174/1871530320666200909092908. Epub 2020 Sep 17. PMID: 32901590.
  2. Muthusami S, Ramachandran I, Krishnamoorthy S, Sambandam Y, Ramalingam S, Queimado L, Chaudhuri G, and Kumaran RI. Regulation of microRNAs in inflammation-associated colorectal cancer: A Mechanistic Approach. Endocr Metab Immune Disord Drug Targets. 2021 Jan 26; 21(1):67-76. doi: 10.2174/1871530320666200917112802. Epub 2020 Sep 17. PMID: 32940190.
  3. Manyanga J. Electronic Cigarettes: Implications on Cancer Risk and Cisplatin Resistance in Oral Epithelial Cells. Order No. 28030538 The University of Oklahoma Health Sciences Center, 2020. ProQuest Dissertations Publishing. 2021 Jan 20.
  4. Manyanga J, Ganapathy V, Bouharati C, Mehta T, Sadhasivam B, Acharya P, Zhao D, and Queimado L. Electronic cigarette aerosols alter the expression of cisplatin transporters and increase drug resistance in oral cancer cells. Sci Rep. 2021 Jan 19; 11(1):1821. doi: 10.1038/s41598-021-81148-0. PMID: 33469038. PMCID: PMC7815770.
  5. Tackett AP, Keller-Hamilton B, Smith CE, Hebert ET, Metcalf JP, Queimado L, Stevens EM, Wallace SW, McQuaid EL, and Wagener TL. Evaluation of Respiratory Symptoms Among Youth e-Cigarette Users. JAMA Netw Open. 2020 Oct 1; 3(10):e2020671. doi: 10.1001/jamanetworkopen.2020.20671. PMID: 33048131.
  6. 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; 13(12):e0210147. doi: 10.1371/journal.pone.0210147. eCollection 2018. PMID: 30596800. PMCID: PMC6312322.
  7. 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. PMID: 29802233. PMCID: PMC6004470. (IF: 9.661).
  8. 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; 12(5):e0177780. doi: 10.1371/journal.pone.0177780. eCollection 2017. PMID: 28542301. PMCID: PMC5436899. (IF: 3.54).
  9. 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-generation and third-generation electronic cigarette users. Tob Control, 2017 Mar; 26(e1):e23-e28. doi:10.1136/tobaccocontrol-2016-053041. Epub 2016 Oct 11. PMID: 27729564. PMCID: PMC5574194. (IF: 5.933).
  10. Hinkl D, Krischer J, Mincy C, Queimado L, and Eapen A. Fra-1 Expression in Salivary Gland Cancer Cells. J Dent Oral Biol. 2016 Nov; 1(4):1018.
  11. 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 Mar; 48(3):265-272. doi: 10.1038/ng.3502. Epub 2016 Feb 1. PMID: 26829750. PMCID: PMC4767593. (IF: 29.352).
  12. Ganapathy V, Ramachandran I, Rubenstein DA, 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. PMID: 26817069. Re-printed (Tobacco Use Prevention and Cessation Issue).
  13. Ganapathy V, Ramachandran I, Rubenstein DA, and Queimado L. Detection of in vivo DNA damage induced by very low doses of mainstream and sidestream smoke extracts using a novel assay. Am J Prev Med. 2015 Jan; 48(1 Suppl 1):S102-110. doi: 10.1016/j.emepre.2014.08.017. PMID: 25528699. (IF: 4.281). Manuscript recognized as a landmark study by Action to Quit (April, 2015).
  14. 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 May 22; 5:e1246, doi: 10.1038/cddis.2014.219. PMID: 24853424. PMCID: PMC4047921. (IF: 5.177).
  15. 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 RM, and Nör JE. Characterization of tumorigenic cell lines from the recurrence and lymph node metastasis of a human salivary mucoepidermoid carcinoma. Oral Oncol. 2013 Nov; 49(11):1059-1066. doi: 10.1016/j.oraloncology.2013.08.004. Epub 2013 Sep 12. PMID: 24035723. PMCID: PMC3821871. (IF: 3.029).
  16. 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.
  17. 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 Aug; 130(2):377-382. doi: 10.1016/j.ygyno.2013.04.054. Epub 2013 Apr 28. PMID: 23632208. (IF: 3.687).
  18. Ramachandran I, Thavathiru E, Ramalingam S, Natarajan G, Mills WK, Benbrook DM, Zuna R, Lightfoot S, Reis A, Anant S, and Queimado L. Wnt inhibitory factor 1 inducs apoptosis and inhibits cervical cancer growth, invasion and angiogenesis in vivo. Oncogene. 2012 May 31; 31(22):2725-2737. doi: 10.1038/onc.2011.455. Epub 2011 Oct 17. PMID: 22002305. (IF: 8.559). Awarded Best Paper of Year at OUHSC.
  19. Reis AM, Mills WK, Ramachandran I, Friedberg EC, Thompson D, and Queimado L. Targeted detection of in vivo endogenous DNA base damage reveals preferential base excision repair in the transcribed strand. Nucleic Acids Res. 2012 Jan; 40(1):206-219. doi: 10.1093/nat/gkr704. Epub 2011 Sep 12. PMID: 21911361. PMCID: PMC3245927. (IF: 8.808).
  20. Lin HY, Landersdorfer CB, London D, Meng R, Lim CU, Lin C, Lin S, Tang HY, Brown D, Van Scoy B, Kulawy R, Queimado L, Drusano GL, Louie A, Davis FB, Mousa SA, and Davis PJ. Pharmacodynamic modeling of anti-cancer activity of tetraiodothyroacetic acid in a perfused cell culture system. PLoS Comput Biol. 2011 Feb 3; 7(2):e1001073. doi: 10.1371/journal.pcbi.1001073. PMID: 21304935. PMCID: PMC3033367. (IF: 4.829).