Ahmad R. Safa, PhD
H. H. Gregg Professor of Cancer Research
2017-present Member, Editorial Board, Journal of Biochemistry and Cell Biology
2017-present Member, Editorial Board, Journal of Advances in Breast Cancer Research and
2017-present International Journal of Cell Science & Molecular Biology (IJCSMB)
2016-present Member, Editorial Board, Journal of Cancer Research and Therapeutic Oncology
2016-present Member, Editorial Board, Journal of Drug Research and Development
2012-present Member, Advisory Editorial Board, World Journal of Pharmacology
2008-present Member, Editorial Board, Journal of Cell Death
2009-present Member, Editorial Board, International Journal of Biochemistry and Molecular
2010-present Member, Editorial Board, Medicinal Chemistry
2013-present Member, Advisory Editorial Board, Advances in Cancer Drug Targets
2012-2015 Member, Editorial Board , Journal of Biomarkers in Drug Development
2010-2014 Member, Editorial Board, Journal of Drug Metabolism and Toxicology
2012-2014 Member, Editorial Board , Open Journal of Apoptosis
2012-2014 Member, Editorial Board, Dataset Papers in Biology
2001-2012 Member, Editorial Board, Molecular Cancer Therapeutics
1996-1998 Member, Editorial Board, Investigational New Drugs
Safa AR, Glover CJ, Meyers MB, Biedler JL, Felsted RL. Vinblastine photoaffinity labeling of a high molecular weight surface membrane glycoprotein specific for multidrug-resistant cells. J Biol Chem 1986; 261:6137-6140.
Cornwell MM, Safa AR, Felsted RL, Gottesman MM, Pastan I. Membrane vesicles from multidrug-resistant human cancer cells contain a specific 150,000-170,000 Dalton protein detected by photoaffinity labeling. Proc Natl Acad Sci USA 1986; 83:3847-3850.
Safa AR. Photoaffinity labeling of the multidrug-resistance-related P-glycoprotein with photoactive analogs of verapamil. Proc Natl Acad Sci USA 1988; 85:7187-7191.
Safa AR, Stern RK, Choi K, Agresti M, Tamai I, Mehta ND, Roninson IB. Molecular basis of preferential resistance to colchicine in multidrug-resistant human cells conferred by Gly-1856Val-185 substitution in P-glycoprotein. Proc Natl Acad Sci USA 1990; 87:7225-7229.
Tamai I, Safa AR. Competitive interaction of cyclosporins with the Vinca alkaloid binding site of P-glycoprotein in multidrug resistant cells. J Biol Chem 1990; 265:16509-16513.
Tamai I, Safa AR. Azidopine noncompetitively interacts with vinblastine and cyclosporin A binding to P-glycoprotein in multidrug resistant cells. J Biol Chem 1991; 266:16796-16800.
Sinicrope FA, Dudeja PK, Bissonnette BM Safa AR, Brasitus TA. Modulation of P-glycoprotein-mediated drug transport by alteration in lipid fluidity of rat liver canalicular membrane vesicles. J Biol Chem 1992; 267:24995-25002.
Safa AR, Agresti M, Bryk D, Tamai I. N-(p-azido-3[125I]iodo-phenethyl)Spiperone binds to specific regions of P-glycoprotein and another multidrug binding protein, Spiperophilin, in human neuroblastoma cells. Biochemistry 1994; 33:256-265.
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 1997; 14:499-506.
Ogretmen B, McCauley MD, Safa AR. Molecular mechanisms of loss of β2-microglobulin expression in drug resistant breast cancer sublines and its involvement in drug resistance. Biochemistry 1998; 37:11679-11691.
Ogretmen B, Safa AR. Identification and characterization of the MDR1 promoter- enhancing factor 1 (MEF 1) in the multidrug resistant HL-60/VCR human acute myeloid leukemia cell line. Biochemistry 2000; 39:194-204.
Wu C-H, 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, and is downregulated in its doxorubicin resistant variant. Oncogene 2002; 21, 5160-5174.
Zhong X-L, Safa AR. RNA helicase A in the MEF1 transcription factor complex up-regulates the
MDR1 gene in multidrug-resistant cancer cells. J Biol Chem 2004; 279:17134-17141.
Park S-J, Wu C-H, Gordon JD, Zhong X-L, Emami A, Safa AR. Taxol induces caspase-10-dependent apoptosis. J Biol Chem 2004; 279:51057-51067.
Choi M-R, Najafi F, Safa AR, Drexler HCA. Analysis of changes in the proteome of HL-60 cells induced by the proteasome inhibitor PSI. Biochem Pharmacol 2008; 75:2276-2288.
Wu C-H, Kao C, Safa AR. TRAIL recombinant adenovirus triggered robust apoptosis in P-glycoprotein bearing multidrug resistant HL-60/Vinc cells preferentially through the death receptor DR5. Hum Gene Ther 2008; 19:731-743.
Day TW, Huang S, Safa AR. c-FLIP knockdown induces ligand-independent DR5-, FADD-, caspase-8-, and caspase-9-dependent apoptosis in breast cancer cells. Biochem Pharmacol 2008; 76:1694-1704.
Huang S, Day TW, Choi MR, Safa AR. Human beta-galactoside alpha-2,3-sialyltransferase (ST3Gal III) attenuated Taxol-induced apoptosis in ovarian cancer cells by downregulating caspase-8 activity. Mol Cell Biochem 2009; 331:81-88.
Shen F, Bailey BJ, Chu S, Bence AK, Xue X, Erickson P, Safa AR, Beck WT, Erickson LC. Dynamic assessment of mitoxantrone resistance and modulation of multidrug resistance by PSC833 in multidrug resistant human cancer cells. J Pharmacol Exp Ther. 2009; 330:423-429.
Day TW, Wu C-H, Safa AR. Etoposide induces protein kinase C δ- and caspase-3-dependent apoptosis in neuroblastoma cancer cells. Mol Pharmacol 2009; 76:632-40.
Bijangi-Vishehsaraei K, Saadatzadeh MR, Huang S, Murphy, MP, Safa AR. 4-(4-chloro-2-methylphenoxy)-N-hydroxybutanamide (CPH) targets mRNA of the c-FLIP variants and induces apoptosis in MCF-7 human breast cancer cells. Molec Cell Biochem 2010; 342:133-142.
Park S-J, Bijangi-Vishehsaraei K, and Safa AR. Selective TRAIL-triggered apoptosis due to overexpression of TRAIL death receptor 5 (DR5) in P-glycoprotein-bearing multidrug resistant CEM/VBL1000 human leukemia cells. Int J Biochem and Molec Biol 2010; 1:90-100.
Huang S, Bijangi-Vishehsaraei K, Saadatzadeh MR, Safa AR. Human GM3 synthase attenuates Taxol-triggered apoptosis associated with downregulation of Caspase-3 in ovarian cancer cells. J. Cancer Therapy 2012; 3:504-510.
Safa AR. Roles of c-FLIP in apoptosis, necroptosis, and autophagy. J Carcinogene Mutagene J Carcinogene Mutagene 2013, S6:1-9.
Safa AR, Saadatzadeh MR, Cohen-Gadol AA, Pollok KE, Bijangi-Vishehsaraei K. Glioblastoma stem cells (GSCs) epigenetic plasticity and interconversion between differentiated non-GSCs and GSCs. Genes Dis. 2015; 2:152-163.
Prabhu L, Han W, Chen L, Özlem D,, Sandusky G, Sun E, Wang J, Mo J, Zeng L, Safa A, Amaro R, Korc M, Zhang Z-Y, Lu T. Adapting AlphaLISA high throughput screen to discovers a novel small-molecule inhibitor targeting protein arginine methyltransferase 5 in pancreatic and colorectal cancers. Oncotarget 2017, 8:39963-39977.
Bijangi-Vishehsaraei, K, Saadatzadeh MR, Wang H, Nguyen A, Kamocka MM, Cai W, Cohen-Gadol AA, Halum SL, Sarkaria JN, Pollok KE, and Safa AR. Sulforaphane suppresses growth of glioblastoma multiforme (GBM) cells, GBM stem cell-like spheroids, and tumor xenografts through multiple cell signaling pathways. J Neurosurgery, 2017 Jan 6:1-12. doi: 10.3171/2016.8.JNS161197. [Epub ahead of print].
Titles & Appointments
- Professor of Pharmacology & Toxicology
Targeting multiple signaling pathways in glioblastoma multiforme (GBM) and pancreatic cancer stem cells to eradicate these drug- and radiation-resistant cells; molecular mechanisms of drug-induced apoptosis; mechanisms of acquired resistance to cancer chemotherapeutic agents.
Investigating role of the anti-apoptotic protein, cellular FLICE-like inhibitory protein (c-FLIP) expressed a long form (c-FLIPL) and short form in resistance to anticancer agents and the cytokine tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). c-FLIP is required for breast cancer, glioblastoma, and pancreatic cancer growth and is a relevant therapeutic target for the treatment of these cancers. We use siRNAs and compounds that degrade/and or inhibit transcription of c-FLIP isoforms with conventional anticancer agents as well as compounds that cause apoptosis in cancer stem cells (CSCs) to eradicate these cancers.
Histone deacetylase 6 (HDAC6) is a cytoplasmic deacetylase that regulates critical biological processes by deacetylating various non-histone proteins. Combination treatment with agents targeting different specific tumor cell characteristics will likely be necessary to successfully eliminate CSCs. The hypothesis is that targeting multiple signaling pathways in CSCs. Our recent research uses combination of HDAC6 inhibitors plus cytotoxic anticancer drugs to eliminate breast cancer, glioblastoma, and pancreatic cancer.