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 and accuracy as a screening tool for head and neck cancer. We are now exploring PADDA for the assessment of tobacco-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. 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, 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). PMCID: PMC4767593
  2. Ganapathy V, Ramachandran I, Rubenstein D, 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, 48 (1 Suppl 1):S102-10, 2015. (IF: 4.527) PMID: 25528699
  3. Ramachandran I, Gillies E, Fonseca I, Kaufman KM, Sureban SM, Houchen CW, Reis A, Queimado L. Wnt inhibitory factor 1 inhibits cancer stemness and induces cellular senescence in human salivary gland tumor cells. Cell Death Dis. 22;5:e1246, 2014. (IF: 6.044).PMCID: PMC4047921.
  4. Warner KA, Adams A, Bernardi L, Nor C, Herwig K, Zhang Z, McLean SA, Helman J, Wolf GT, Divi V, Queimado L, Kaye FJ, Castilho R, Nör JE. Tumorigenic human salivary mucoepidermoid carcinoma cell lines. Oral Oncology, 49(11):1059-1066, 2013. (IF: 3.607). PMCID: PMC3821871
  5. Ramachandran I, Thavathiru E, Ramalingam S, Natarajan G, Mills W, Benbrook D, Zuna R, Lightfoot S, Reis AMC, Anant S and Queimado L. Wnt inhibitory factor 1 induces apoptosis and inhibits cervical cancer growth, invasion and angiogenesis in vivo. Oncogene, 31:2725–2737, 2012. (IF: 8.459).  PMID: 22002305. Awarded Best Paper of Year 2012 at OUHSC.
  6. Moxley KM, Benbrook DM, Queimado L, Zuna RE, Thompson D, McCumber M, Premkumar P, Thavathiru E, Hines L, 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. Gynecologic Oncology, 130(2): 377-38, 2013. (IF: 3.774) PMID:23632208
  7. Reis AMC, Mills W, Ramachandran I, Friedberg EC, Thompson DM, Queimado L. Targeted detection of in vivo endogenous DNA base damage reveals preferential base excision repair in the transcribed strand. Nucleic Acids Research, 40(1):206-219, 2012. (IF: 9.112) PMCID: PMC3245927
  8. Borden RC, Saunders JE, Berryhill WE, Krempl GA, Thompson DM, and Queimado L. Hyaluronic Acid Hydrogel Sustains the Delivery of Dexamethasone across the Round Window Membrane. Audiology and Neurotology, 16:1-11, 2011. (IF: 2.465) PMID: 20431286
  9. Landersdorfer C, Davis PJ, London D, Meng R, Lim C-U, Lin C, Lin S, Tang H-Y, Brown D, Kulawy K, Queimado L, Drusano G, Louie A, Davis FB, Mousa SA, and L. H-Y, Pharmacodynamic Modeling of Anti-Cancer Activity of Tetraiodothyroacetic Acid in a Perfused Cell Culture System. PLoS Computational Biology,7(2):p. e1001073, 2011. (IF: 5.215) PMCID: PMC3033367
  10. Ramalingam S, Natarajan G, Schafer C, May R, Ramachandran I, Queimado L, Houchen CW and Anant S. Novel intestinal splice variants of RNA binding protein CUGBP2:Isoform specific effects on mitotic catastrophe. Am J Physiol Gastrointest Liver Physiol, 294:G971-81, 2008. (IF: 3.798) PMCID: PMC4464843.
  11. Hatfield MD, Reis AMC, Obeso, D, Cook JR, Thompson DM, Rao M, Friedberg EC, Queimado L. Identification of MMS19 domains with distinct functions in NER and transcription. DNA Repair, 5:914-924, 2006. (IF: 5.868) PMID:16797255