Ahmad R. Safa

Ahmad R. Safa, PhD

H. H. Gregg Professor of Cancer Research

Bio

Dr. Safa received his Bachelor of Science in Biology from the University of Esfahan, Iran, in 1973. He received his MS in General Biology in 1976, a MS in Molecular Cellular and Developmental Biology (MCDB) in 1977, and a PhD in MCDB in 1980 from Iowa State University. He joined the University of Louisville as a Postdoctoral Fellow from 1980-1983 and subsequently was a Visiting Fellow and a guest researcher at the National Cancer Institute (NCI) from 1983-1987.

In 1987, he accepted a position as an Assistant Professor of Medicine at the University of Chicago and was Director of the Laboratories of Pharmacology and Pharmacokinetics, and Molecular Pharmacology, respectively in the Section of Hematology/Oncology from 1990-1996. In 1996, he accepted a tenured Associate Professor Position in the Department of Experimental Oncology, Medical University of South Carolina (MUSC), and was promoted to tenured Professor in 1999. Dr. Safa was Director of the Drug Resistance Program at Hollings Cancer Center at MUSC from 1998-1999. In 1999, he joined the faculty of the Indiana University School of Medicine as H.H. Gregg Professor of Cancer Research, and Professor of Pharmacology and Toxicology.

Dr. Safa has been investigating the molecular and biochemical mechanisms of intrinsic and acquired resistance to chemotherapeutic drugs, apoptosis (cell death) in cancer cells, cancer stem cells, drug discovery and development, and cancer treatment. His lab is particularly interested in multi-targeted therapy of brain cancer, breast cancer, and pancreatic tumors through modulation of the death receptor signaling pathway in cancer cells.

Dr. Safa served on the Experimental Therapeutics 1 Study Section at the NCI from 1988-2002, has been an Ad hoc Grant Reviewer, Center for Scientific Review, Drug Discovery and Molecular Pharmacology Study Section since 2003, Tumor Cell Biology (TCB) Study Section, and other National Cancer Institutes (NCI) Study Sections. He has been a member of the Editorial Board of International Journal of Cell Science & Molecular Biology (IJCSMB), Journal of Cancer Research and Therapeutic Oncology. Drug Research and Development, World Journal of Pharmacology, Medicinal Chemistry, Journal of Drug Metabolism and Toxicology, International Journal of Biochemistry and Molecular Biology, Journal of Cell Death, Molecular Cancer Therapeutics, and Investigational New Drugs.

EDITORIAL POSITIONS
2017-present: Member, Editorial Board, Journal of Biochemistry and Cell Biology
2017-present: Member, Editorial Board, Journal of Advances in Breast Cancer Research and Development
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 Biology
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

Key Publications

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].

 

Connect


asafa@iupui.edu 


(317) 278-4952 


Pharmacology & Toxicology
MS 550 PHTX
Indianapolis, IN


  

Titles & Appointments

  • Professor of Pharmacology & Toxicology