Research Interest:
Molecular Sphingolipid and Cancer Biology; Regulation of Telomerase and Telomeres by Sphingolipid Signaling; Roles of Sphingolipids in Human Lung and Head and Neck Cancer and Therapy
Positions: Program Leader, Lipid Signaling in Cancer Program, Hollings Cancer Center, Medical University of South Carolina
Selected Publications:
| 1. | Hoeferlin LA, Fekry B, Ogretmen B, Krupenko SA, Krupenko NI. Folate Stress Induces Apoptosis via p53-Dependent de novo Ceramide Synthesis and Up-Regulation of Ceramide Synthase 6. J Biol Chem. ., 2013.
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| | 2. | Saddoughi SA, Ogretmen B. Diverse functions of ceramide in cancer cell death and proliferation. Adv Cancer Res. .117:37-58, 2013.
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| | 3. | Jiang W, Ogretmen B. Ceramide stress in survival versus lethal autophagy paradox: ceramide targets autophagosomes to mitochondria and induces lethal mitophagy. Autophagy. .9(2):258-9, 2012. PMCID: PMC3552895
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| | 4. | Saddoughi SA, Gencer S, Peterson YK, Ward KE, Mukhopadhyay A, Oaks J, Bielawski J, Szulc ZM, Thomas RJ, Selvam SP, Senkal CE, Garrett-Mayer E, De Palma RM, Fedarovich D, Liu A, Habib AA, Stahelin RV, Perrotti D, Ogretmen B. Sphingosine analogue drug FTY720 targets I2PP2A/SET and mediates lung tumour suppression via activation of PP2A-RIPK1-dependent necroptosis. EMBO Mol Med. .5(1):105-21, 2012. PMCID: PMC3569657
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| | 5. | Beckham TH, Lu P, Jones EE, Marrison T, Lewis CS, Cheng JC, Ramshesh VK, Beeson G, Beeson CC, Drake RR, Bielawska A, Bielawski J, Szulc ZM, Ogretmen B, Norris JS, Liu X. LCL124, a cationic analog of ceramide, selectively induces pancreatic cancer cell death by accumulating in mitochondria. J Pharmacol Exp Ther. .344(1):167-78, 2012. PMCID: PMC3533418
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| | 6. | Sentelle RD, Senkal CE, Jiang W, Ponnusamy S, Gencer S, Selvam SP, Ramshesh VK, Peterson YK, Lemasters JJ, Szulc ZM, Bielawski J, Ogretmen B. Ceramide targets autophagosomes to mitochondria and induces lethal mitophagy. Nat Chem Biol. .8(10):831-8, 2012.
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| | 7. | Syed I, Szulc ZM, Ogretmen B, Kowluru A. L- threo -C6-pyridinium-ceramide bromide, a novel cationic ceramide, induces NADPH oxidase activation, mitochondrial dysfunction and loss in cell viability in INS 832/13 ß-cells. Cell Physiol Biochem. .30(4):1051-8, 2012.
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| | 8. | Ponnusamy S, Selvam SP, Mehrotra S, Kawamori T, Snider AJ, Obeid LM, Shao Y, Sabbadini R, Ogretmen B. Communication between host organism and cancer cells is transduced by systemic sphingosine kinase 1/sphingosine 1-phosphate signalling to regulate tumour metastasis. EMBO Mol Med. .4(8):761-75, 2012. PMCID: PMC3494075
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| | 9. | Bareford MD, Hamed HA, Allegood J, Cruickshanks N, Poklepovic A, Park MA, Ogretmen B, Spiegel S, Grant S, Dent P. Sorafenib and pemetrexed toxicity in cancer cells is mediated via SRC-ERK signaling. Cancer Biol Ther. .13(9):793-803, 2012.
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| | 10. | Meyers-Needham M, Lewis JA, Gencer S, Sentelle RD, Saddoughi SA, Clarke CJ, Hannun YA, Norell H, da Palma TM, Nishimura M, Kraveka JM, Khavandgar Z, Murshed M, Cevik MO, Ogretmen B. Off-target function of the Sonic hedgehog inhibitor cyclopamine in mediating apoptosis via nitric oxide-dependent neutral sphingomyelinase 2/ceramide induction. Mol Cancer Ther. .11(5):1092-102, 2012.
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| | 11. | Booth L, Cazanave SC, Hamed HA, Yacoub A, Ogretmen B, Chen CS, Grant S, Dent P. OSU-03012 suppresses GRP78/BiP expression that causes PERK-dependent increases in tumor cell killing. Cancer Biol Ther. .13(4):224-36, 2012. PMCID: PMC3336069
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| | 12. | Meyers-Needham M, Ponnusamy S, Gencer S, Jiang W, Thomas RJ, Senkal CE, Ogretmen B. Concerted functions of HDAC1 and microRNA-574-5p repress alternatively spliced ceramide synthase 1 expression in human cancer cells. EMBO Mol Med. .4(2):78-92, 2011. PMCID: PMC3376837
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| | 13. | Senkal CE, Ponnusamy S, Manevich Y, Meyers-Needham M, Saddoughi SA, Mukhopadyay A, Dent P, Bielawski J, Ogretmen B. Alteration of ceramide synthase 6/C16-ceramide induces activating transcription factor 6-mediated endoplasmic reticulum (ER) stress and apoptosis via perturbation of cellular Ca2+ and ER/Golgi membrane network. J Biol Chem. .286(49):42446-58, 2011. PMCID: PMC3234959
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| | 14. | Baran Y, Bielawski J, Gunduz U, Ogretmen B. Targeting glucosylceramide synthase sensitizes imatinib-resistant chronic myeloid leukemia cells via endogenous ceramide accumulation. J Cancer Res Clin Oncol. .137(10):1535-44, 2011.
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| | 15. | Saddoughi SA, Garrett-Mayer E, Chaudhary U, O'Brien PE, Afrin LB, Day TA, Gillespie MB, Sharma AK, Wilhoit CS, Bostick R, Senkal CE, Hannun YA, Bielawski J, Simon GR, Shirai K, Ogretmen B. Results of a phase II trial of gemcitabine plus doxorubicin in patients with recurrent head and neck cancers: serum C18-ceramide as a novel biomarker for monitoring response. Clin Cancer Res. .17(18):6097-105, 2011. PMCID: PMC3176980
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| | 16. | Salas A, Ponnusamy S, Senkal CE, Meyers-Needham M, Selvam SP, Saddoughi SA, Apohan E, Sentelle RD, Smith C, Gault CR, Obeid LM, El-Shewy HM, Oaks J, Santhanam R, Marcucci G, Baran Y, Mahajan S, Fernandes D, Stuart R, Perrotti D, Ogretmen B. Sphingosine kinase-1 and sphingosine 1-phosphate receptor 2 mediate Bcr-Abl1 stability and drug resistance by modulation of protein phosphatase 2A. Blood. .117(22):5941-52, 2011. PMCID: PMC3112039
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| | 17. | Shirai K, Kaneshiro T, Wada M, Furuya H, Bielawski J, Hannun YA, Obeid LM, Ogretmen B, Kawamori T. A role of sphingosine kinase 1 in head and neck carcinogenesis. Cancer Prev Res (Phila). .4(3):454-62, 2011. PMCID: PMC3342666
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| | 18. | Separovic D, Bielawski J, Pierce JS, Merchant S, Tarca AL, Bhatti G, Ogretmen B, Korbelik M. Enhanced tumor cures after Foscan photodynamic therapy combined with the ceramide analog LCL29. Evidence from mouse squamous cell carcinomas for sphingolipids as biomarkers of treatment response. Int J Oncol. .38(2):521-7, 2010. PMCID: PMC3349972
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| | 19. | Park MA, Hamed HA, Mitchell C, Cruickshanks N, Dash R, Allegood J, Dmitriev IP, Tye G, Ogretmen B, Spiegel S, Yacoub A, Grant S, Curiel DT, Fisher PB, Dent P. A serotype 5/3 adenovirus expressing MDA-7/IL-24 infects renal carcinoma cells and promotes toxicity of agents that increase ROS and ceramide levels. Mol Pharmacol. .79(3):368-80, 2010. PMCID: PMC3061366
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| | 20. | Ponnusamy S, Meyers-Needham M, Senkal CE, Saddoughi SA, Sentelle D, Selvam SP, Salas A, Ogretmen B. Sphingolipids and cancer: ceramide and sphingosine-1-phosphate in the regulation of cell death and drug resistance. Future Oncol. .6(10):1603-24, 2010. PMCID: PMC3071292
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| | 21. | Park MA, Reinehr R, Häussinger D, Voelkel-Johnson C, Ogretmen B, Yacoub A, Grant S, Dent P. Sorafenib activates CD95 and promotes autophagy and cell death via Src family kinases in gastrointestinal tumor cells. Mol Cancer Ther. .9(8):2220-31, 2010. PMCID: PMC2933415
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| | 22. | Park MA, Mitchell C, Zhang G, Yacoub A, Allegood J, Häussinger D, Reinehr R, Larner A, Spiegel S, Fisher PB, Voelkel-Johnson C, Ogretmen B, Grant S, Dent P. Vorinostat and sorafenib increase CD95 activation in gastrointestinal tumor cells through a Ca(2+)-de novo ceramide-PP2A-reactive oxygen species-dependent signaling pathway. Cancer Res. .70(15):6313-24, 2010. PMCID: PMC2918282
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| | 23. | Yacoub A, Hamed HA, Allegood J, Mitchell C, Spiegel S, Lesniak MS, Ogretmen B, Dash R, Sarkar D, Broaddus WC, Grant S, Curiel DT, Fisher PB, Dent P. PERK-dependent regulation of ceramide synthase 6 and thioredoxin play a key role in mda-7/IL-24-induced killing of primary human glioblastoma multiforme cells. Cancer Res. .70(3):1120-9, 2010. PMCID: PMC2890071
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| | 24. | Demarse NA, Ponnusamy S, Spicer EK, Apohan E, Baatz JE, Ogretmen B, Davies C. Direct binding of glyceraldehyde 3-phosphate dehydrogenase to telomeric DNA protects telomeres against chemotherapy-induced rapid degradation. J Mol Biol. .394(4):789-803, 2009. PMCID: PMC2789664
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| | 25. | Patwardhan GA, Zhang QJ, Yin D, Gupta V, Bao J, Senkal CE, Ogretmen B, Cabot MC, Shah GV, Sylvester PW, Jazwinski SM, Liu YY. A new mixed-backbone oligonucleotide against glucosylceramide synthase sensitizes multidrug-resistant tumors to apoptosis. PLoS One. .4(9):e6938, 2009. PMCID: PMC2735002
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| | 26. | Senkal CE, Ponnusamy S, Bielawski J, Hannun YA, Ogretmen B. Antiapoptotic roles of ceramide-synthase-6-generated C16-ceramide via selective regulation of the ATF6/CHOP arm of ER-stress-response pathways. FASEB J. .24(1):296-308, 2009. PMCID: PMC2797032
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| | 27. | Separovic D, Bielawski J, Pierce JS, Merchant S, Tarca AL, Ogretmen B, Korbelik M. Increased tumour dihydroceramide production after Photofrin-PDT alone and improved tumour response after the combination with the ceramide analogue LCL29. Evidence from mouse squamous cell carcinomas. Br J Cancer. .100(4):626-32, 2009. PMCID: PMC2653738
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| | 28. | White-Gilbertson S, Mullen T, Senkal C, Lu P, Ogretmen B, Obeid L, Voelkel-Johnson C. Ceramide synthase 6 modulates TRAIL sensitivity and nuclear translocation of active caspase-3 in colon cancer cells. Oncogene. .28(8):1132-41, 2009. PMCID: PMC2648838
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| | 29. | Mukhopadhyay A, Saddoughi SA, Song P, Sultan I, Ponnusamy S, Senkal CE, Snook CF, Arnold HK, Sears RC, Hannun YA, Ogretmen B. Direct interaction between the inhibitor 2 and ceramide via sphingolipid-protein binding is involved in the regulation of protein phosphatase 2A activity and signaling. FASEB J. .23(3):751-63, 2008. PMCID: PMC2653988
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| | 30. | Ponnusamy S, Alderson NL, Hama H, Bielawski J, Jiang JC, Bhandari R, Snyder SH, Jazwinski SM, Ogretmen B. Regulation of telomere length by fatty acid elongase 3 in yeast. Involvement of inositol phosphate metabolism and Ku70/80 function. J Biol Chem. .283(41):27514-24, 2008. PMCID: PMC2562072
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| | 31. | Corcoran CA, He Q, Ponnusamy S, Ogretmen B, Huang Y, Sheikh MS. Neutral sphingomyelinase-3 is a DNA damage and nongenotoxic stress-regulated gene that is deregulated in human malignancies. Mol Cancer Res. .6(5):795-807, 2008. PMCID: PMC2642592
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| | 32. | Saddoughi SA, Song P, Ogretmen B. Roles of bioactive sphingolipids in cancer biology and therapeutics. Subcell Biochem. .49:413-40, 2008. PMCID: PMC2636716
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| | 33. | Karahatay S, Thomas K, Koybasi S, Senkal CE, Elojeimy S, Liu X, Bielawski J, Day TA, Gillespie MB, Sinha D, Norris JS, Hannun YA, Ogretmen B. Clinical relevance of ceramide metabolism in the pathogenesis of human head and neck squamous cell carcinoma (HNSCC): attenuation of C(18)-ceramide in HNSCC tumors correlates with lymphovascular invasion and nodal metastasis. Cancer Lett. .256(1):101-11, 2007. PMCID: PMC2084356
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| | 34. | Wooten-Blanks LG, Song P, Senkal CE, Ogretmen B. Mechanisms of ceramide-mediated repression of the human telomerase reverse transcriptase promoter via deacetylation of Sp3 by histone deacetylase 1. FASEB J. .21(12):3386-97, 2007.
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| | 35. | Baran Y, Salas A, Senkal CE, Gunduz U, Bielawski J, Obeid LM, Ogretmen B. Alterations of ceramide/sphingosine 1-phosphate rheostat involved in the regulation of resistance to imatinib-induced apoptosis in K562 human chronic myeloid leukemia cells. J Biol Chem. .282(15):10922-34, 2007.
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| | 36. | Kraveka JM, Li L, Szulc ZM, Bielawski J, Ogretmen B, Hannun YA, Obeid LM, Bielawska A. Involvement of dihydroceramide desaturase in cell cycle progression in human neuroblastoma cells. J Biol Chem. .282(23):16718-28, 2007. PMCID: PMC2084375
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| | 37. | Senkal CE, Ponnusamy S, Rossi MJ, Bialewski J, Sinha D, Jiang JC, Jazwinski SM, Hannun YA, Ogretmen B. Role of human longevity assurance gene 1 and C18-ceramide in chemotherapy-induced cell death in human head and neck squamous cell carcinomas. Mol Cancer Ther. .6(2):712-22, 2007.
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| | 38. | Kitatani K, Idkowiak-Baldys J, Bielawski J, Taha TA, Jenkins RW, Senkal CE, Ogretmen B, Obeid LM, Hannun YA. Protein kinase C-induced activation of a ceramide/protein phosphatase 1 pathway leading to dephosphorylation of p38 MAPK. J Biol Chem. .281(48):36793-802, 2006.
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| | 39. | Ogretmen B. Sphingolipids in cancer: regulation of pathogenesis and therapy. FEBS Lett. .580(23):5467-76, 2006.
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| | 40. | Senkal CE, Ponnusamy S, Rossi MJ, Sundararaj K, Szulc Z, Bielawski J, Bielawska A, Meyer M, Cobanoglu B, Koybasi S, Sinha D, Day TA, Obeid LM, Hannun YA, Ogretmen B. Potent antitumor activity of a novel cationic pyridinium-ceramide alone or in combination with gemcitabine against human head and neck squamous cell carcinomas in vitro and in vivo. J Pharmacol Exp Ther. .317(3):1188-99, 2006.
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| | 41. | Sultan I, Senkal CE, Ponnusamy S, Bielawski J, Szulc Z, Bielawska A, Hannun YA, Ogretmen B. Regulation of the sphingosine-recycling pathway for ceramide generation by oxidative stress, and its role in controlling c-Myc/Max function. Biochem J. .393(Pt 2):513-21, 2006. PMCID: PMC1360701
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| | 42. | Wooten LG, Ogretmen B. Sp1/Sp3-dependent regulation of human telomerase reverse transcriptase promoter activity by the bioactive sphingolipid ceramide. J Biol Chem. .280(32):28867-76, 2005.
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| | 43. | Johnson KR, Johnson KY, Crellin HG, Ogretmen B, Boylan AM, Harley RA, Obeid LM. Immunohistochemical distribution of sphingosine kinase 1 in normal and tumor lung tissue. J Histochem Cytochem. .53(9):1159-66, 2005.
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| | 44. | Rossi MJ, Sundararaj K, Koybasi S, Phillips MS, Szulc ZM, Bielawska A, Day TA, Obeid LM, Hannun YA, Ogretmen B. Inhibition of growth and telomerase activity by novel cationic ceramide analogs with high solubility in human head and neck squamous cell carcinoma cells. Otolaryngol Head Neck Surg. .132(1):55-62, 2005.
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| | 45. | Koybasi S, Senkal CE, Sundararaj K, Spassieva S, Bielawski J, Osta W, Day TA, Jiang JC, Jazwinski SM, Hannun YA, Obeid LM, Ogretmen B. Defects in cell growth regulation by C18:0-ceramide and longevity assurance gene 1 in human head and neck squamous cell carcinomas. J Biol Chem. .279(43):44311-9, 2004.
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| | 46. | Ogretmen B, Hannun YA. Biologically active sphingolipids in cancer pathogenesis and treatment. Nat Rev Cancer. .4(8):604-16, 2004.
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| | 47. | Day TA, Deveikis J, Gillespie MB, Joe JK, Ogretmen B, Osguthorpe JD, Reed SG, Richardson MS, Rossi M, Saini R, Sharma AK, Stuart RK. Salivary gland neoplasms. Curr Treat Options Oncol. .5(1):11-26, 2004.
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| | 48. | Sundararaj KP, Wood RE, Ponnusamy S, Salas AM, Szulc Z, Bielawska A, Obeid LM, Hannun YA, Ogretmen B. Rapid shortening of telomere length in response to ceramide involves the inhibition of telomere binding activity of nuclear glyceraldehyde-3-phosphate dehydrogenase. J Biol Chem. .279(7):6152-62, 2003.
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| | 49. | Kraveka JM, Li L, Bielawski J, Obeid LM, Ogretmen B. Involvement of endogenous ceramide in the inhibition of telomerase activity and induction of morphologic differentiation in response to all-trans-retinoic acid in human neuroblastoma cells. Arch Biochem Biophys. .419(2):110-9, 2003.
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| | 50. | Wu CH, Gordon J, Rastegar M, Ogretmen B, Safa AR. Proteinase-3, a serine protease which mediates doxorubicin-induced apoptosis in the HL-60 leukemia cell line, is downregulated in its doxorubicin-resistant variant. Oncogene. .21(33):5160-74, 2002.
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| | 51. | Ogretmen B, Pettus BJ, Rossi MJ, Wood R, Usta J, Szulc Z, Bielawska A, Obeid LM, Hannun YA. Biochemical mechanisms of the generation of endogenous long chain ceramide in response to exogenous short chain ceramide in the A549 human lung adenocarcinoma cell line. Role for endogenous ceramide in mediating the action of exogenous ceramide. J Biol Chem. .277(15):12960-9, 2002.
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| | 52. | Chalfant CE, Rathman K, Pinkerman RL, Wood RE, Obeid LM, Ogretmen B, Hannun YA. De novo ceramide regulates the alternative splicing of caspase 9 and Bcl-x in A549 lung adenocarcinoma cells. Dependence on protein phosphatase-1. J Biol Chem. .277(15):12587-95, 2002.
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| | 53. | Ogretmen B, Hannun YA. Updates on functions of ceramide in chemotherapy-induced cell death and in multidrug resistance. Drug Resist Updat. .4(6):368-77, 2001.
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| | 54. | Chalfant CE, Ogretmen B, Galadari S, Kroesen BJ, Pettus BJ, Hannun YA. FAS activation induces dephosphorylation of SR proteins; dependence on the de novo generation of ceramide and activation of protein phosphatase 1. J Biol Chem. .276(48):44848-55, 2001.
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| | 55. | Boujaoude LC, Bradshaw-Wilder C, Mao C, Cohn J, Ogretmen B, Hannun YA, Obeid LM. Cystic fibrosis transmembrane regulator regulates uptake of sphingoid base phosphates and lysophosphatidic acid: modulation of cellular activity of sphingosine 1-phosphate. J Biol Chem. .276(38):35258-64, 2001.
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| | 56. | Ogretmen B, Kraveka JM, Schady D, Usta J, Hannun YA, Obeid LM. Molecular mechanisms of ceramide-mediated telomerase inhibition in the A549 human lung adenocarcinoma cell line. J Biol Chem. .276(35):32506-14, 2001.
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| | 57. | Ogretmen B, Schady D, Usta J, Wood R, Kraveka JM, Luberto C, Birbes H, Hannun YA, Obeid LM. Role of ceramide in mediating the inhibition of telomerase activity in A549 human lung adenocarcinoma cells. J Biol Chem. .276(27):24901-10, 2001.
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| | 58. | Kraveka JM, Schady D, Obeid LM, Ogretmen B. Immunoprecipitation of human telomerase reverse transcriptase with telomerase activity. Anal Biochem. .291(1):166-9, 2001.
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| | 59. | Ogretmen B, Safa AR. Identification and characterization of the MDR1 promoter-enhancing factor 1 (MEF1) in the multidrug resistant HL60/VCR human acute myeloid leukemia cell line. Biochemistry. .39(1):194-204, 2000.
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| | 60. | Ogretmen B, Barredo JC, Safa AR. Increased expression of lung resistance-related protein and multidrug resistance-associated protein messenger RNA in childhood acute lymphoblastic leukemia. J Pediatr Hematol Oncol. .22(1):45-9, 2000.
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| | 61. | Ogretmen B, Safa AR. Negative regulation of MDR1 promoter activity in MCF-7, but not in multidrug resistant MCF-7/Adr, cells by cross-coupled NF-kappa B/p65 and c-Fos transcription factors and their interaction with the CAAT region. Biochemistry. .38(7):2189-99, 1999.
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| | 62. | Ogretmen B, McCauley MD, Safa AR. Molecular mechanisms of loss of beta 2-microglobulin expression in drug-resistant breast cancer sublines and its involvement in drug resistance. Biochemistry. .37(33):11679-91, 1998.
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| | 63. | Ogretmen B, Bahadori HR, McCauley MD, Boylan A, Green MR, Safa AR. Co-ordinated over-expression of the MRP and gamma-glutamylcysteine synthetase genes, but not MDR1, correlates with doxorubicin resistance in human malignant mesothelioma cell lines. Int J Cancer. .75(5):757-61, 1998.
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| | 64. | Ogretmen B, Bahadori H, McCauley M, Boylan A, Green M, Safa AR. Lack of correlation of MRP and gamma-glutamylcysteine synthetase overexpression with doxorubicin resistance due to increased apoptosis in SV40 large T-antigen-transformed human mesothelial cells. Cancer Chemother Pharmacol. .42(6):441-6, 1998.
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| | 65. | Ogretmen B, Safa AR. Expression of the mutated p53 tumor suppressor protein and its molecular and biochemical characterization in multidrug resistant MCF-7/Adr human breast cancer cells. Oncogene. .14(4):499-506, 1997.
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| | 66. | Ogretmen B, Safa AR. Down-regulation of apoptosis-related bcl-2 but not bcl-xL or bax proteins in multidrug-resistant MCF-7/Adr human breast cancer cells. Int J Cancer. .67(5):608-14, 1996.
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| | 67. | Ogretmen B, Carpo C, Safa AR. Site-directed mutagenesis by unique site elimination using filamentous phage-derived ssDNA templates for plasmids that are resistant to denaturation. Biotechniques. .21(2):209-13, 1996.
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| | 68. | Ogretmen B, Ratajczak H, Gendel SM, Stark BC. Effects of sodium saccharin and linoleic acid on mRNA levels of Her2/neu and p53 in a human breast epithelial cell line. Cancer Lett. .102(1-2):91-9, 1996.
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| | 69. | Ogretmen B, Safa AR. Mini-preparation of total RNA for RT-PCR from cultured human cells. Biotechniques. .19(3):374-6, 1995.
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| | 70. | Ogretmen B, Ratajczak H, Kats A, Stark BC, Gendel SM. Effects of staining of RNA with ethidium bromide before electrophoresis on performance of northern blots. Biotechniques. .14(6):932-5, 1993.
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| | 71. | Liu SC, Ogretmen B, Chuang YY, Stark BC. Selection and characterization of alpha-amylase-overproducing recombinant Escherichia coli containing the bacterial hemoglobin gene. Appl Microbiol Biotechnol. .38(2):239-42, 1992.
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