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Thomas Jefferson University - Eric Wickstrom, PhD
Eric Wickstrom, PhD

Biochemistry & Molecular Biology
Thomas Jefferson University
Jefferson Medical College
Department of Biochemistry & Molecular Biology
Professor Appointed: 1992
Mailing Address
233 South 10th Street, 209 & 219 Bluemle Life Sciences Building
Philadelphia, Pennsylvania 19107-5541
United States
Contact Information
Phone: (215) 955-4578
Fax: (215) 955-4580
eric@tesla.jci.tju.edu
Personal Web Site
Qualifications
Ph.D., Chemistry, University of California, Berkeley, 1972

B.S. with Honor, Biology, California Institute of Technology, Pasadena, 1968

Expertise and Research Interests
Cancer covers a broad spectrum of diseases, in every tissue of the body. Tissues are composed of cells, which normally grow slowly, under the tight control of a network of regulatory genes. The slow accumulation of activating mutations in growth genes, and inactivating mutations in suppressor genes, eventually allows a cell to grow out of control. Relapse is due to the development of resistant cells, rather than the escape of sensitive cells, suggesting the need for new approaches to treatment of the disease.

This laboratory is developing cancer gene-specific RNA and DNA derivatives against cancer genes in the signal transduction pathway for use as diagnostics and therapeutics for cancers. The biological systems being studied include the CCND1, HER2, EGFR, and KRAS2 cancer genes in breast cancer, ovarian cancer, pancreatic cancer, colon cancer and lung cancer. To move our approaches into the clinic, we must identify the most efficacious RNA and DNA target sequences, their mechanisms and physiological effects. We must design and synthesize potent RNA and DNA analogs capable of surviving in the bloodstream following administration must be synthesized, and we must determine their structures.

To see active cancer gene mRNAs from outside the body, we synthesize peptide analogs that enable receptor-specific uptake of peptide nucleic acids (PNA)that hybridize to target mRNAs in the cytoplasm. By adding a radionuclide chelator to one end of a PNA-peptide, we can radioimage cancerous or precancerous regions by single photon emission computed tomography (SPECT) or positron emission tomography (PET). By using a branched dendrimer PNA-peptide with multiple chelators to bind gadolinium, we might see cancer gene mRNA by magnetic resonance imaging (MRI). With a near infrared fluorophore, we can observe the target mRNAs by optical imaging.

Three-dimensional touch-and-feel molecular modeling and surgical simulation are being integrated with our genetic imaging scans. This study includes touch-and-feel simulations of the kinetic pathway of ligand docking with macromolecules in order to cull out kinetically unfavorable ligand designs.

Both the genetic imaging approach and the virtual reality approach are being applied to the problem of varying levels of MAOA mRNA and D2DR mRNA in certain brain cells that react strongly to cocaine. We are developing genetic imaging agents to visualize and quantitate those two mRNAs in vivo. Similarly, we are developing genetic imaging agents that target the NLGN4Y mRNA, which might be implicated in the development of autism spectrum disorders, when overexpressed.

On the therapeutic side, we can destroy IRS1 cancer gene mRNA in breast cancer cells and MKP1, BIM, and BCL2 cancer gene mRNAs in acute lymphoblastic leukemia cells with short interfering RNA (siRNA) sequences. Finally, we have begun to study blocking of a microRNA, miR-21, which is overexpressed in breast cancer cells. Nuclease-resistant sequences complementary to miR-21 might interdict breast cancer cell growth.

Laboratory Staff
Other Expertise
EXPERIENCE
Jefferson Medical College, Thomas Jefferson University
1992-1996: Professor of Pharmacology; Member, Jefferson Cancer Institute
1997-present: Professor of Microbiology & Immunology; Member, Kimmel Cancer Center; Member, Cardeza Foundation for Hematologic Research
2002-2005: Professor of Biochemistry & Molecular Pharmacology
2005-present: Professor of Biochemistry & Molecular Biology
2008-present: Adjunct Professor of Radiology, College of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania

TEACHING EXPERIENCE (1992-present)
A. Thomas Jefferson University
Graduate: BI 515 General Biochemistry I; BI 612 Protein Function and Dysfunction; BI 614 Protein Structure and Function; BI 522 Experimental Principles in Molecular Biology; BI/PR 710,720,730 Biochemical/Pharmacological Literature Seminar; BT 411 Protein Purification and Characterization; GC 550 Foundations in Biomedical Sciences; GE 652 Molecular Basis of Cancer; PR 613 Structural Biology I; TE 521 Tissue Engineering

UNIVERSITY, COLLEGE, AND DEPARTMENTAL COMMITTEE SERVICE (1992-present)
Thomas Jefferson University
Strategic Planning Working Group on Cancer and Cancer Biology, 2005-2006
Clinical Cancer Research Review Committee, 1993-2009
Animal Resources Committee, 1997-8
Jefferson Medical College
Committee on Faculty Affairs, 2004-2009
Committee on Research, 2005-2008
Kimmel Cancer Center
2008-present: KCC Membership Committee
2008-present: KCC Prostate Cancer Working Group
2006-present: KCC Endocrine Mechanisms and Hormone Action in Cancer Program Committee
Seminar Committee, 2005-present
CD Facility Committee, 2000-2006
Development Therapeutics Committee, 1997-2006
NMR Facility Committee, 1993-2002
Computer Committee, 1993-7
Structural Biology Committee, 1993-7
Biochemistry and Molecular Biology
2007-present: Curriculum Committee (Chair, 2008-)

INVITED LECTURES (2008-present)

1. Genetic imaging. Center for Targeted Therapeutics and Translational Nanomedicine, University of Pennsylvania, Philadelphia, Pennsylvania, September 21, 2011.
2. Three dimensional projection environment for molecular design and surgical simulation. US Army Telemedicine & Advanced Technology Research Center Product Line Review, Frederick, Maryland, March 29, 2011.
3. Genetic imaging. Tinoco 80th Birthday Symposium, University of California, Berkeley, California, June 26, 2010.
4. Molecular Designs for Diagnosis and Therapy, Department of Bioengineering, University of California, Merced, April 13, 2009.
5. PET Imaging of Activated Cancer Gene mRNA in Tumors. New Frontiers of Science in Radiochemistry and Instrumentation for Radionuclide Imaging Workshop, Department of Energy, Bethesda, Maryland, November 5, 2008.
6. Multiple Radionuclide Nanoparticles for Genetic Imaging. New Frontiers of Science in Radiochemistry and Instrumentation for Radionuclide Imaging Workshop, Department of Energy, Bethesda, Maryland, November 5, 2008.
7. Scintigraphic imaging of KRAS mRNA in human pancreas cancer xenografts with ([111In]DO3A)n-poly(diamidopropanoyl)m-PNA-D(Cys-Ser-Lys-Cys) hybridization probes. Biophysical & Biomolecular Symposium: Targeted Delivery of Proteins and Nucleotides, American Chemical Society 236th Annual Meeting, Philadelphia, Pennsylvania, August 20, 2008.
8. Multicomponent molecular detection of breast cancer cells using nanotube electronic devices specific for cell surface receptors. Emerging Technologies: Nanobiotechnology, American Chemical Society 236th Annual Meeting, Philadelphia, Pennsylvania, August 20, 2008.
Industrial Relevance
Noninvasive molecular diagnostics and therapeutics for cancer, inflammation, drug addiction, and autism. To translate mRNA imaging into clinical cancer management, we have licensed the breast and lung indications to Molecular Targeting Technologies, our collaborators on two NIH joint grants.
Keywords
Antibiotics; Antineoplastic; Antisense Nucleic Acid; Athymic Mouse; B Lymphocyte; Breast Cancer; Cancer Biology; Cancer; Carcinogenesis; Cancer Prevention; Cell Cycle; Cell Differentiation; Chemical Model; Chemical Synthesis; Circular Dichroism; DNA; Drug Delivery Systems; Drug Design Synthesis Production; Gene Expression; Growth Inhibitor; Heterologous Transplantation; Implants; Liposome; Liquid Chromatography; Lymphoma; Magnetic Resonance Imaging; Mass Spectrometry; Messenger RNA; Neoplasm Cancer Chemotherapy; Neoplasm Cancer Genetics; Neoplasm Cancer Pharmacology; Neoplasm Cancer Immunotherapy; Neoplasm Cancer Transplantation; Neoplastic Cell; Neoplastic Growth; Nonhuman Therapy Evaluation; Nucleic Acid Chemical Synthesis; Nucleic Acid Hybridization; Nucleic Acid Sequence; Nucleic Acid Sequence; Oligonucleotide; Oncogene; Ovarian Cancer; Pharmacokinetics; Phosphonate; Phosphoric Ester; Radionuclide Therapy; Stereochemistry; Thiophosphate; Transgenic Animal;
Languages
Russian
Publications
  • Sethi, D., Chen, C.-P.,Jing, R.-Y., Thakur, M. L., and Wickstrom, E. (2012) Fluorescent peptide-PNA chimeras for imaging monoamine oxidase A mRNA in neuronal cells. Bioconjugate Chemistry 23(2):158-163
  • Thakur, M. L., Zhang, K., Paudyal, B., Devadhas, D., Covarrubias, M., Cheng, C., Gray, B., Wickstrom, E., and Pak, K.-Y. (2012) Targeting apoptosis for optical imaging of infection. Molecular Imaging and Biology 14: in press.
  • Wickstrom, E., Chen, C.-P., Devadhas, D., Wampole, M., Jin, Y.-Y., Sanders, J.M., Kairys, J.C., Ankeny, M.L., Hu, R., Barner, K.E., Steiner, K.V., and Thakur, M.L. (2011) Three dimensional projection environment for molecular design and surgical simulation. Studies in Health Technologies and Informatics 163:691-695.
  • Chen, C.-P. and Wickstrom, E. (2010) Daptomycin-tetraethyleneglycol-bisphosphonate-Ti6Al4V foils resist Staphylococcus aureus colonization. Bioconjugate Chemistry 21(11):1978-1986.
  • Velasco, V., Wickstrom, E., and Panchapakesan, B. (2010) Applications of nanoparticles for molecular targeting and selective destruction of breast cancer cells. In Chaughule, R. S. and Ramanujan, R. V., eds., Nanoparticles: Synthesis, Characterization and Applications, American Scientific Publishers, Stevenson Ranch CA, Chap. 13, ISBN 1-58883-180-9.
  • Amirkhanov, N.V., Zhang, K., Aruva, M.R., Thakur, M.L., and Wickstrom, E. (2010) Scintigraphic imaging of KRAS2 mRNA in human pancreas cancer xenografts with (111In-DO3A)n-poly(diamidopropanoate)m-PNA-D(Cys-Ser-Lys-Cys) hybridization probes Bioconjugate Chemistry 21(4):731-740.
  • Panchapakesan, B., Caprara, R., Velasco, V., Loomis, J., King, B., Xu, P., Burkhead, T., Sethu, P., Stallons, J., McGregor, W. G., Rai, S. N., Kloecker, G., and Wickstrom, E. (2010) Micro- and nanotechnology approaches for capturing circulating tumor cells. Cancer Nano, DOI 10.1007/s12645-010-0007-z.
  • Opitz, A.W., Thakur, M.L., Wickstrom, E., and Wagner, N.J. (2010) Physiologically based pharmacokinetics of molecular imaging nanoparticles for mRNA detection determined in tumor-bearing mice. Oligonucleotides 20(3):117-125.
  • Thakur, M.L., Zhang, K., Devadhas, D., Pestell, R.G., and Wickstrom, E. (2010) Imaging spontaneous MMTVneu transgenic mammary tumors: Targeting metabolic activity versus genetic products. Journal of Nuclear Medicine 51(1):106-111.
  • Wickstrom, E., and Thakur, M. L. (2010) Genetic and molecular approaches to imaging breast cancer. In: Sauter, E. R., and Daly, M. B., eds., Breast Cancer Risk Reduction and Early Detection, Springer, Boston, Chap. 9, 163-182.
  • Mukherjee, A., Wickstrom, E., and Thakur, M. L. (2009) Imaging oncogene expression. European Journal of Radiology 70(2) 265-273.
  • Shao, N., Wickstrom, E., and Panchapakesan, B. (2008) Single nanotube-antibody biosensor arrays for detection of circulating breast cancer cells. Nanotechnology 19(October):465101 (11 pp).
  • Antoci, V., Jr., Adams, C.S., Parvizi, J., Davidson, H.M., Composto, R.J., Freeman, T.A., Wickstrom, E., Ducheyne, P., Jungkind, D., Shapiro, I.M., and Hickok, N.J. (2008) The inhibition of Staphylococcus epidermidis biofilm formation by vancomycin-modified titanium alloy and implications for the treatment of periprosthetic infection. Biomaterials 29(35):46844690.
  • Zhang, C.-M., Liu, C.-P., Christian, T., Gamper, H., Rozenski, J., Randolph, J.B., Wickstrom, E., Cooperman, B.S., and Hou, Y.-M. (2008) Pyrrolo-C as a molecular probe for monitoring conformations of the tRNA 3' end. RNA 14(10):2245-2253.
  • Amirkhanov, N.V., Dimitrov, I., Opitz, A.W., Zhang, K., Lackey, J.P., Cardi, C.A., Lai, S., Thakur, M.L., and Wickstrom, E. (2008) Design of (Gd-DO3A)n-polydiamidopropanoate-peptide nucleic acid-D(Cys-Ser-Lys-Cys) magnetic resonance contrast agents. Biopolymers 89(12):1061-1076.
  • Tian, X., Michal, A.M., Li, P., Wolfe, H.R., Waldman, S.A., and Wickstrom, E. (2008) STa peptide analogs for probing guanylyl cyclase C. Peptide Science 90(5):713-723.
  • Millar, H.J., Nemeth, J.A., McCabe, F.L., and Wickstrom, E. (2008) Circulating human interleukin 8 as an indicator of cancer progession in a nude rat orthotopic human NSCLC model. Cancer Epidemiology, Biomarkers & Prevention 17(8):2180-2187.
  • Zhang, K., Aruva, M.R., Shanthly, N., Cardi, C.A., Rattan, S., Patel, C., Kim, C., McCue, P.A., Wickstrom, E., and Thakur, M.L. (2008) PET imaging of VPAC1 expression in experimental and spontaneous prostate cancer. Journal of Nuclear Medicine 49(1):112-121.
  • Cesarone, G., Edugupanti, O.P., Chen, C.-P., and Wickstrom, E. (2007) Insulin receptor substrate 1 knockdown in human MCF7 ER+ breast cancer cells by nuclease-resistant IRS1 siRNA conjugated to a disulfide-bridged D-peptide analog of insulin-like growth factor 1. Bioconjugate Chemistry 18(6):1831-1840.
  • Tian, X., Aruva, M.R., Zhang, K., Cardi, C.A., Thakur, M.L., and Wickstrom, E. (2007) PET imaging of CCND1 mRNA in human MCF7 estrogen receptor-positive breast cancer xenografts with an oncogene-specific [64Cu]DO3A-PNA-peptide radiohybridization probe. Journal of Nuclear Medicine 48(10):1699-1707.
  • Chen, C.-P., Zeiger, A.R., and Wickstrom, E. (2007) Bactericidal activity of extended 9-glycyl-minocycline derivatives. Bioorganic & Medicinal Chemistry Letters 17(23):6558-6562.
  • Zhang, K., Aruva, M.R., Shanthly, N., Cardi, C.A., Patel, C.A., Rattan, S., Cesarone, G., Wickstrom, E., and Thakur, M.L. (2007) Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase activating peptide (PACAP) receptor specific peptide analogues for PET imaging of breast cancer: In vitro/in vivo evaluation. Regulatory Peptides 144(1-3):91-100.
  • Yakubov, L.A., Rogachev, V.A., Likhacheva, A.C., Bogachev, S.S., Sebeleva, T.E., Shilov, A.G., Baiborodin, S.I., Petrova, N.A., Mechetina, L.V., Shurdov, M.A., and Wickstrom, E. (2007) Natural human gene correction by small extracellular genomic DNA fragments. Cell Cycle 6(18):2293-2301.
  • Chakrabarti, A., Zhang, K., Aruva, M.R., Cardi, C.A., Opitz, A.W., Wagner, N.J., Thakur, M.L., and Wickstrom, E. (2007) Radiohybridization PET imaging of KRAS G12D mRNA expression in human pancreas cancer xenografts with [64Cu]DO3A-peptide nucleic acid-peptide nanoparticles. Cancer Biology & Therapy 6(6):948-956.
  • Shao, N., Lu, S., Wickstrom, E., and Panchapakesan, B. (2007) Integrated molecular targeting of IGF1R and Her2 surface receptors and destruction of breast cancer cells using single wall carbon nanotubes. Nanotechnology 18(7):315101 (9pp).
  • Duffy, K.T. and Wickstrom, E. (2007) Zebrafish tp53 knockdown extends the survival of irradiated zebrafish embryos more effectively than the p53 inhibitor pifithrin-alpha. Cancer Biology & Therapy 6(5):675-678.
  • Antoci, V., Jr., King, S.B., Jose, B., Parvizi, J., Zeiger, A.R., Wickstrom, E., Freeman, T.A., Composto, R.J., Ducheyne, P., Shapiro, I.M., Hickok, N.J., and Adams, C.S. (2007) Vancomycin covalently bonded to titanium alloy prevents bacterial colonization. Journal of Orthopaedic Research 25(7):858-866.
  • Edupuganti, O.P., Antoci, V., Jr., King, S.B., Jose, B., Adams, C.S., Parvizi, J., Shapiro, I.M., Zeiger, A.R., Hickok, N.J., and Wickstrom, E. (2007) Vancomycin covalently bound to Ti6Al4V pins provides longterm inhibition of Staphylococcus aureus colonization. Bioorganic & Medicinal Chemistry Letters 17(10):2692-2696.
  • McAleer, M. F., Duffy, K. T., Davidson, W. R., Kari, G., Dicker, A. P., Rodeck, U., and Wickstrom, E. (2006) Antisense inhibition of cyclin D1 expression is equivalent to flavopiridol for radiosensitization of zebrafish embryos. International Journal of Radiation Oncology Biology Physics 66(2):546551.
  • Quadros, M. R. D., Connelly, S., Kari, C., Abrams, M. T., Wickstrom, E., and Rodeck, U. (2006) EGFR-dependent downregulation of Bim in epithelial cells requires MAPK and PKC-d activities. Cancer Biology and Therapy 5(5):498-504.
  • Panchapakesan, B., Cesarone, G., Lu, S., Teker, K., and Wickstrom, E. (2006) Conductivity sensing of breast cancer cells by carbon nanotubes coated with monoclonal antibodies against IGF1 receptor. NanoBiotechnology 1(4):353-360.
  • Cesarone, G., Garofalo, C., Abrams, M. T., Igoucheva, O., Alexeev, V., Yoon, K., Surmacz, E., and Wickstrom, E. (2006) Specific reduction of insulin receptor substrate 1 (IRS-1) expression in MCF7 cells by RNA interference enhances tamoxifen-mediated cell death. Journal of Cellular Biochemistry 98(2):440-450.
  • Efimov, V., Chakhmakhcheva, O., and Wickstrom, E. (2005) Synthesis and application of negatively charged PNA analogues. Nucleosides, Nucleotides, and Nucleic Acids 24(10):1853-1874.
  • Teker, K., Sirdeshmukh, R., Sivakumar, K., Lu, S., Wickstrom, E., Wang, H.-N., Vo-Dinh, T., and Panchapakesan, B. (2005) Applications of carbon nanotubes for cancer research. NanoBiotechnology 1(2):171-182.
  • Panchapakesan, B., Teker, K., Lu, S., Sivakumar, K., Cesarone, G., and Wickstrom, E. (2005) Single wall carbon nanotube nanobombs kill cancer cells. NanoBiotechnology 1(2):133-140.
  • Tian, X., Aruva, M. R., Wolfe, H. R., Qin, W., Sauter, E. R., Thakur, M. L., Waldman, S. A., and Wickstrom, E. (2005) Tumor-targeting peptide-PNA-peptide chimeras for imaging overexpressed oncogene mRNAs Nucleosides, Nucleotides, and Nucleic Acids 24:1085-1091.
  • Amirkhanov, N. V. and Wickstrom, E. (2005) Synthesis of novel polydiamidopropanoate dendrimer PNA-peptide chimeras for non-invasive magnetic resonance imaging of cancer. Nucleosides, Nucleotides, and Nucleic Acids 24:423-426.
  • Chakrabarti, A., Aruva, M. R., Sajankila, S. P., Thakur, M. L., and Wickstrom, E. (2005) Synthesis of novel PNA-peptide chimera for non-invasive imaging of cancer. Nucleosides, Nucleotides, and Nucleic Acids 24:409-414.
  • Jose, B., Antoci, V., Jr., Zeiger, A. R., Wickstrom, E., and Hickok, N. J. (2005) Vancomycin covalently bonded to titanium beads kills Staphylococcus aureus. Chemistry & Biology 12(9:1041-1048.
  • Duffy, K. T., McAleer, M. F., Davidson, W. R., Kari, L., Kari, C., Liu, C.-G., Farber, S. A., Cheng, K. C., Mest, J. R., Wickstrom, E., Dicker, A. P., and Rodeck, U. (2005) Coordinate control of cell cycle regulatory genes in zebrafish development tested by cyclin D1 knockdown with morpholino phosphorodiamidates and hydroxyprolyl-phosphono peptide nucleic acids. Nucleic Acids Research 33(15):49144921.
  • Abrams, M. T., Robertson, N. M., Litwack, G., and Wickstrom, E. (2005) Evaluation of glucocorticoid sensitivity in 697 pre-B acute lymphoblastic leukemia cells after overexpression or silencing of MAP kinase phosphatase-1. Journal of Cancer Research and Clinical Oncology 131(6):347-354.
  • Tian, X., Aruva, M. R., Qin, W., Zhu, W., Sauter, E. R., Thakur, M. L., and Wickstrom, E. (2005) Noninvasive molecular imaging of MYC mRNA expression in human breast cancer xenografts with a Tc-99m-peptide-PNA-peptide chimera. Bioconjugate Chemistry 16(1):70-79.
  • Abrams, M. T., Robertson, N. M., Yoon, K., and Wickstrom, E. (2004) Inhibition of glucocorticoid sensitivity by RNA interference against BIM in acute lymphoblastic leukemia cells. Journal of Biological Chemistry 279(53):55809-55817.
  • Tian, X., Aruva, M. R., Qin, W., Zhu, W., Duffy, K. T., Sauter, E. R., Thakur, M. L., and Wickstrom, E. (2004) External imaging of CCND1 cancer gene activity in experimental human breast cancer xenografts with Tc-99m-peptide-PNA-peptide chimeras. Journal of Nuclear Medicine 45(12):2070-2082.
  • Parvizi, J., Wickstrom, E., Zeiger, A. R., Adams, C. S., Purtill, J. J., Sharkey, P. F., Hozack, W. J., Shapiro, I. M., Rothman, R. H., and Hickok, N. J. (2004) Titanium surface with biologic activity against infection. Clinical Orthopaedics and Related Research 429(1):33-38.
  • Wickstrom, E., Choob, M., Urtishak, K. A., Tian, X., Sternheim, N., Archdeacon, J., Efimov, V.A., and Farber, S. A. (2004) Sequence specificity of alternating hydroxyprolyl/phosphono peptide nucleic acids against zebrafish embryo mRNAs. Journal of Drug Targeting 12(6):363-372.
  • Wickstrom, E., Urtishak, K. A., Choob, M., Tian, X., Sternheim, N., Rubinstein, A., and Farber, S. A. (2004) Downregulation of gene expression with negatively charged PNAs in zebrafish embryos. In Detrich, W., Westerfield, M., and Zon, L., eds., Methods in Cell Biology 77: ZEBRAFISH: Genetics, Genomics, and Informatics, 2nd ed., Elsevier/Academic Press, San Diego, Chap. 8, 137-158.
  • Hargis, M.T., Storck, C.W., Wickstrom, E., Yakubov, L.A., Leeper, D.B., and Coss, R.A. (2004) Hsp27 antisense oligonucleotides sensitize the microtubular cytoskeleton of Chinese hamster ovary cells grown at low pH to 42°C-induced reorganization. International Journal of Hyperthermia 20:491-502.
  • Thakur, M. L., Aruva, M. R., Gariepy, J., Acton, P., Rattan, S., Wickstrom, E., and Alavi, A. (2004) PET imaging of oncogene overexpression using Cu-64-labeled peptide. Journal of Nuclear Medicine 45:1381-1389.
  • Wickstrom, E., Tian, X., Amirkhanov, N., Chakrabarti, A., Aruva, M., Rao, P. S., Thakur, M. L., Qin, W., Zhu, W., and Sauter, E. R. (2004) Radionuclide-peptide nucleic acid diagnosis and treatment of pancreatic cancer. In Phillips, M. I., ed., Methods in Molecular Medicine 106: Antisense Therapeutics, 2nd ed. Humana Press, Totowa NJ, Chap. 8, 135-192.
  • Chakrabarti, A., Desai, P. and Wickstrom, E. (2004) Transposon Tn7 TnsD protein binds to evolutionarily conserved eukaryotic homologs of its Escherichia coli attTn7 target. Biochemistry 43: 2941-2946.
  • Vorobjev, P. E., Smith, J. B., Pyshnaya, I. A., Levina, A. S., Zarytova, V. F., and Wickstrom, E. (2003) Site-specific cleavage of RNA and DNA by complementary DNA-bleomycin A5 conjugates. Bioconjugate Chemistry 14(6):1307-1313.
  • Tian, X., Aruva, M., Rao, P. S., Qin, W., Read, P., Sauter, E. R., Thakur, M. L., and Wickstrom, E. (2003) Imaging oncogene expression. In Cho-Chung, Y. S., Gewirtz, A. M., and Stein, C. A., eds., Therapeutic Oligonucleotides: Antisense, RNAi, Triple Helix, DNA Decoys, and DNA Chips, Annals of the New York Academy of Sciences 1002:165-188.
  • Urtishak, K. A., Choob, M., Tian, X., Artishek, N., Talbot, S., Wickstrom, E., and Farber, S. A. (2003) Targeted gene knockdown in zebrafish using negatively charged peptide nucleic acid mimics. Developmental Dynamics 228:405-413.
  • Wickstrom, E., Thakur, M. L., and Sauter, E. R. (2003) Receptor-specific targeting with complementary peptide nucleic acids conjugated to peptide analogs and radionuclides. Letters in Peptide Science 10(3/4):191-214.
  • Butz, J., Wickstrom, E., and Edwards, J. S. (2003) Characterization of mutations and loss of heterozygosity of p53 and K-RAS2 in pancreatic cancer cell lines by immobilized polymerase chain reaction. BMC Biotechnology 3:11.
  • Rao, P. S., Tian, X., Qin, W., Sauter, E. R., Thakur, M. L., and Wickstrom, E. (2003) Tc-99m-peptide-PNA probes for oncogene mRNAs in tumors. Nuclear Medicine Communications 24:857-863.
  • Wickstrom, E., Tian, X., Rao, P. S., Thakur, M. L., Qin, W., and Sauter, E. R. (2002) Oncogene mRNA imaging with Tc-99m-chelator-PNA-peptides. Russian Chemical Bulletin, International Edition 51:1083-1099.
  • Vorob'ev PE, Pyshnyi DV, Wickstrom E, Zarytova VF. (2002)[Cleavage of RNA in a hybrid duplex by E. coli ribonuclease H. III. Substrate characteristics of hybrid duplexes of RNA and oligodeoxyribonucleotides containing a bleomycin A5 residue]. Bioorganicheskaia Khimiia. 28(4): 332-340.
  • Tian X, Wickstrom E. Continuous solid-phase synthesis and disulfide cyclization of peptide-PNA-peptide chimeras. Organic Letters. 4(23): 4013-6, Nov 2002
  • Vorobjev, P. E., Pyshnaya, I. A., Wickstrom, E., and Zarytova, V. F. (2002) Directed cleavage of RNA within an imperfect complementary complex by conjugates of bleomycin A5 with oligonucleotide. Russian Chemical Bulletin, International Edition 51:1187-1189.
  • Vorobjev, P. E., Pyshnyi, D. V., Wickstrom, E., and Zarytova, V. F. (2002) Cleavage of RNA in hybrid duplexes by E. coli ribonuclease H: III. Substrate properties of RNA duplex complexes with oligodeoxyribonucleotides containing a bleomycin A5 residue. Russian Journal of Bioorganic Chemistry 28:300-307.
  • Fu, Z. F., Wickstrom, E., Dietzschold, B., and Koprowski, H. (2002) Antigenomic Oligonucleotides for Treatment of Infection by Negative-Stranded Nonsegmented RNA Viruses. U.S. patent no. 6,355,621.
  • Wickstrom, E. (2001) Oligonucleotide treatment of RAS-induced tumors in nude mice. Molecular Biotechnology 18, 35-55.
  • Lesnikowski, Z. J., Przepiórkiewicz, M., Tamura, Y., Kaji, H., and Wickstrom, E. Effect of configuration at phosphorus on transport of tetra(thymidine methylphosphonate)s across organic liquid membrane. Collection of Czechoslovak Chemical Communications. 66: 912-922, 2001
  • Wickstrom, E., and Basu, S. (2001) Peptide Nucleic Acid Conjugates. U.S. patent no. 6,180,767
  • Cleaver SH, Wickstrom E. Transposon Tn7 gene insertion into an evolutionarily conserved human homolog of Escherichia coli attTn7. Gene. 254(1-2): 37-44, Aug 2000
  • Smith JB, Wickstrom E. Preclinical antisense DNA therapy of cancer in mice. Methods in Enzymology. 314: 537-80, 2000.
  • Wickstrom, E., ed. (1999) Antisense Therapeutics. In Frontiers in Bioscience 4, http://www.bioscience.org/current/special/antisens.htm
  • Wickstrom, E., and Cleaver, S. H. (1999) Composition and Method for Targeted Integration into Cells. U.S. patent no. 5,958,775
  • Smith J B, Wickstrom E. Antisense c-myc and immunostimulatory oligonucleotide inhibition of tumorigenesis in a murine B-cell lymphoma transplant model. Journal of The National Cancer Institute. 90(15): 1146-54, 5 Aug 1998
  • Wickstrom E, Smith J B. DNA combination therapy to stop tumor growth. Cancer Journal From Scientific American. 4 Suppl 1: S43-7, May 1998
  • Wickstrom, E., ed. (1998) Clinical Trials of Genetic Therapy with Antisense DNA and DNA Vectors, Marcel Dekker, New York, ISBN 0-8247-0085-6.
  • Smith JB; Wickstrom E. Inhibition of tumorigenesis in a murine B-cell lymphoma transplant model by c-Myc complementary oligonucleotides. Advanced Experimental Medicine and Biology. 451: 17-22, 1998
  • Basu S, Wickstrom E. Synthesis and characterization of a peptide nucleic acid conjugated to a D-peptide analog of insulin-like growth factor 1 for increased cellular uptake. Bioconjugate Chemistry. 8(4): 481-8, Jul 1997
  • Wickstrom E. Antisense c-myc inhibition of lymphoma growth. Antisense and Nucleic Acid Drug Development. 7(3): 225-8, Jun 1997
  • Wickstrom, E., and Le Bec, C. (1997) Stereospecific Solid Phase Synthesis of Oligodeoxynucleoside Alkylphosphonates by Pentavalent Grignard Coupling. U.S. patent no. 5,703,223
  • Gray G D;Wickstrom E. Rapid measurement of modified oligonucleotide levels in plasma samples with a fluorophore specific for single-stranded DNA. Antisense and Nucleic Acid Drug Development. 7(3): 133-40, Jun 1997
  • Gray G D;Basu S;Wickstrom E. Transformed and immortalized cellular uptake of oligodeoxynucleoside phosphorothioates, 3'-alkylamino oligodeoxynucleotides, 2'-O-methyl oligoribonucleotides, oligodeoxynucleoside methylphosphonates, and peptide nucleic acids. Biochemical Pharmacology. 53(10): 1465-76, 15 May 1997
  • Basu S;Wickstrom E. Temperature and salt dependence of higher order structure formation by antisense c-myc and c-myb phosphorothioate oligodeoxyribonucleotides containing tetraguanylate tracts. Nucleic Acids Research. 25(7): 1327-32, 1 Apr 1997
  • Mazumder A, Uchida H, Neamati N, Sunder S, Jaworska-Maslanka M, Wickstrom E, Zeng F, Jones RA, Mandes RF, Chenault HK, Pommier Y. Probing interactions between viral DNA and human immunodeficiency virus type 1 integrase using dinucleotides. Molecular Pharmacology. 51(4): 567-75, Apr 1997
  • DeLong R K;Nolting A;Fisher M;Chen Q;Wickstrom E;Kligshteyn M;Demirdji S;Caruthers M;Juliano R L. Comparative pharmacokinetics, tissue distribution, and tumor accumulation of phosphorothioate, phosphorodithioate, and methylphosphonate oligonucleotides in nude mice. Antisense and Nucleic Acid Drug Development. 7(2): 71-7, Apr 1997
  • Nolting A;DeLong R K;Fisher M H;Wickstrom E;Pollack G M;Juliano R L;Brouwer K L. Hepatic distribution and clearance of antisense oligonucleotides in the isolated perfused rat liver. Pharmaceutical Research. 14(4): 516-21, Apr 1997
  • Wickstrom, E. (1997) Antisense DNA therapy of Burkitts lymphoma in Eµ-myc transgenic mice. In Weiss, B., ed., Antisense Oligodeoxynucleotides and Antisense RNA as Novel Pharmacological and Therapeutic Agents, CRC Press, Boca Raton FL, 149-169
  • Cheng X;DeLong R K;Wickstrom E;Kligshteyn M;Demirdji S H;Caruthers M H;Juliano R L. Interactions between single-stranded DNA binding protein and oligonucleotide analogs with different backbone chemistries. Journal of Molecular Recognition. 10(2): 101-7, Mar 1997
  • Wickstrom E;Tyson F L. Differential oligonucleotide activity in cell culture versus mouse models. Ciba Foundation Symposium. 209: 124-37; discussion 1, 1997
  • Gray G D;Wickstrom E. Evaluation of anchorage-independent proliferation in tumorigenic cells using the redox dye alamarBlue. Biotechniques. 21(5): 780,782, Nov 1996
  • Lebedev, A. V., and Wickstrom, E. (1996) The chirality problem in P-substituted oligonucleotides. In Trainor, G., ed., Perspectives in Drug Discovery and Design, Vol. 4, ESCOM Science Publishers, Leiden, 17-40
  • Fu Z F;Wickstrom E;Jiang M;Corisdeo S;Yang J;Dietzschold B;Koprowski H. Inhibition of rabies virus infection by an oligodeoxynucleotide complementary to rabies virus genomic RNA. Antisense and Nucleic Acid Drug Development. 6(2): 87-93, 1 Jul 1996
  • Wickstrom, E. (1996) Antisense tumor therapy: activated c-Ha-ras oncogene in the mouse. In Agrawal, S., ed., Methods in Molecular Medicine 2: Antisense Therapeutics, Humana Press, Totowa NJ, 87-108
  • Huang Y;Snyder R;Kligshteyn M;Wickstrom E. Prevention of tumor formation in a mouse model of Burkitt's lymphoma by 6 weeks of treatment with anti-c-myc DNA phosphorothioate. Molecular Medicine. 1(6): 647-58, Sep 1995
  • Hughes J A;Avrutskaya A V;Brouwer K L;Wickstrom E;Juliano R L. Radiolabeling of methylphosphonate and phosphorothioate oligonucleotides and evaluation of their transport in everted rat jejunum sacs. Pharmaceutical Research. 12(6): 817-24, Jun 1995
  • Wickstrom, E. (1995) Nuclease resistant derivatives of antisense DNA. In Akhtar, S., ed., Delivery Systems for Antisense Oligonucleotide Therapeutics, CRC Press, Boca Raton FL, 85-104.
  • Vyazovkina E V;Savchenko E V;Lokhov S G;Engels J W;Wickstrom E;Lebedev A V. Synthesis of specific diastereomers of a DNA methylphosphonate heptamer, d(CpCpApApApCpA), and stability of base pairing with the normal DNA octamer d(TPGPTPTPTPGPGPC). Nucleic Acids Research. 22(12): 2404-9, 25 Jun 1994
  • Vyazovkina E V;Rife J P;Lebedev A V;Wickstrom E. Preparation of trimers and tetramers of mixed sequence oligodeoxynucleoside methylphosphonates and assignment of configurations at the chiral phosphorus. Nucleic Acids Research. 21(25): 5957-63, 25 Dec 1993
  • Gray G D;Hernandez O M;Hebel D;Root M;Pow-Sang J M;Wickstrom E. Antisense DNA inhibition of tumor growth induced by c-Ha-ras oncogene in nude mice. Cancer Research. 53(3): 577-80, 1 Feb 1993
  • Wickstrom E;Bacon T A;Wickstrom E L. Down-regulation of c-MYC antigen expression in lymphocytes of Emu-c-myc transgenic mice treated with anti-c-myc DNA methylphosphonates. Cancer Research. 52(24): 6741-5, 15 Dec 1992
  • Wickstrom, E. (1992) Antisense DNA control of c-myc gene expression, proliferation and differentiation in HL-60 cells. In Murray, J. A. H., ed., Antisense RNA and DNA, Wiley-Liss, New York, 317-334.
  • Wickstrom E. Strategies for administering targeted therapeutic oligodeoxynucleotides. Trends in Biotechnology. 10(8): 281-7, Aug 1992
  • Wickstrom, E. (1992) Antisense DNA therapeutics: neutral analogs and their stereochemistry. In Erickson, R. P., and Izant, J. G., eds., Gene Regulation: Biology of Antisense RNA and DNA, Raven Press, New York, 119-132.
  • Akhtar S;Basu S;Wickstrom E;Juliano R L. Interactions of antisense DNA oligonucleotide analogs with phospholipid membranes (liposomes). Nucleic Acids Research. 19(20): 5551-9, 25 Oct 1991
  • Wickstrom, E., ed. (1991) Prospects for Antisense Nucleic Acid Therapy of Cancer and AIDS, Wiley-Liss, New York, ISBN 0-471-56880-5
  • Farese RV, Standaert ML, Ishizuka T, Yu B, Hernandez H, Waldron C, Watson J, Farese JP, Cooper DR, Wickstrom E. Antisense DNA downregulates protein kinase C isozymes (beta and alpha) and insulin-stimulated 2-deoxyglucose uptake in rat adipocytes. Antisense Research and Development. 1(1): 35-42, Spring 1991
  • Ho PT, Ishiguro K, Wickstrom E, Sartorelli AC. Non-sequence-specific inhibition of transferrin receptor expression in HL-60 leukemia cells by phosphorothioate oligodeoxynucleotides. Antisense Research and Development. 1(4): 329-42, Winter 1991
  • Wickstrom, E., Bacon, T. A., Wickstrom, E. L., Werking, C. M., Palmiter, R. D., Brinster, R. L., and Sandgren, E. P. (1991) Antisense DNA methylphosphonates in c-myc transgenic mice. In Efimov, V. A., ed., International Symposium on Synthetic Oligonucleotides: Problems and Frontiers of Practical Application, Nucleic Acids Research Symposium Series No. 24, Oxford University Press, Oxford, 151-154.
  • Bacon T A;Wickstrom E. Daily addition of an anti-c-myc DNA oligomer induces granulocytic differentiation of human promyelocytic leukemia HL-60 cells in both serum-containing and serum-free media. Oncogene Research. 6(1): 21-32, 1991
  • Bacon T A;Wickstrom E. Walking along human c-myc mRNA with antisense oligodeoxynucleotides: maximum efficacy at the 5' cap region. Oncogene Research. 6(1): 13-9, 1991
  • Campbell J M;Bacon T A;Wickstrom E. Oligodeoxynucleoside phosphorothioate stability in subcellular extracts, culture media, sera and cerebrospinal fluid. Journal of Biochemical and Biophysical Methods. 20(3): 259-67, Mar 1990
  • Daaka Y;Wickstrom E. Target dependence of antisense oligodeoxynucleotide inhibition of c-Ha-ras p21 expression and focus formation in T24-transformed NIH3T3 cells. Oncogene Research. 5(4): 267-75, 1990
  • Lise LD, Jolivet M, Audibert F, Fernandez A, Wickstrom E, Chedid L, Schlesinger DH. Role of the proline residues on the immunogenic properties of a P. falciparum circumsporozoite peptide linked to a carrier protein. Peptide Research. 2(1): 114-9, 1989
  • Muralikrishna P, Wickstrom E. Inducible high expression of the Escherichia coli infC gene subcloned behind a bacteriophage T7 promoter. Gene. 80(2): 369-74, Aug 1989
  • Cook, R. M., Hudson, D., Tsou, D., Teplow, D., Wong, H., Zou, A.-Q., and Wickstrom, E. (1989) Fmoc-mediated solid phase assembly of human immunodeficiency virus tat protein. In Jung, G., and Bayer, E., eds., Peptides 1988, Proceedings of the Twentieth European Peptide Symposium, Walter de Gruyter, Berlin, 187-189.
  • Wickstrom E L;Bacon T A;Gonzalez A;Lyman G H;Wickstrom E. Anti-c-myc DNA increases differentiation and decreases colony formation by HL-60 cells. In Vitro Cellular and Developmental Biology. 25(3 Pt 1): 297-302, Mar 1989
  • Bacon TA, Morvan F, Rayner B, Imbach JL, Wickstrom E. alpha-Oligodeoxynucleotide stability in serum, subcellular extracts and culture media. Journal of Biochemical and Biophysical Methods. 16(4): 311-8, Aug 1988
  • Wickstrom EL, Bacon TA, Gonzalez A, Freeman DL, Lyman GH, Wickstrom E. Human promyelocytic leukemia HL-60 cell proliferation and c-myc protein expression are inhibited by an antisense pentadecadeoxynucleotide targeted against c-myc mRNA. Proceedings of the National Academy of Sciences (USA). 85(4): 1028-32, Feb 1988
  • Wickstrom E, Laing LG. Physical studies of the interaction of Escherichia coli translational initiation factor 3 protein with ribosomal RNA. Methods in Enzymology. 164: 238-58, 1988
  • Heikkila R, Schwab G, Wickstrom E, Loke SL, Pluznik DH, Watt R, Neckers LM. A c-myc antisense oligodeoxynucleotide inhibits entry into S phase but not progress from G0 to G1. Nature. 328(6129): 445-9, Jul 1987
  • Wickstrom E. Escherichia coli ribosomal protein S1 does not protect the 49-nucleotide 3' terminal cloacin fragment of 16 S rRNA from nuclease S1. Biochimica et Biophysica Acta. 868(4): 265-9, Dec 1986
  • Wickstrom E, Heus HA, Haasnoot CA, van Knippenberg PH. Circular dichroism and 500-MHz proton magnetic resonance studies of the interaction of Escherichia coli translational initiation factor 3 protein with the 16S ribosomal RNA 3' cloacin fragment. Biochemistry. 25(10): 2770-7, May 1986
  • Wickstrom E. Nuclease mapping of the secondary structure of the 49-nucleotide 3' terminal cloacin fragment of Escherichia coli 16s RNA and its interactions with initiation factor 3. Nucleic Acids Research. 11(7): 2035-52, Apr 1983
  • Parker KK, Wickstrom E. Crosslinking of Escherichia coli 50S ribosomal subunits with chlorambucilyl oligoprolyl phenylalanyl-tRNA molecular rulers. Nucleic Acids Research. 11(2): 515-24, Jan 1983
  • Skidgel RA, Wickstrom E, Kumamoto K, Erdos EG. Rapid radioassay for prolylcarboxypeptidase (angiotensinase C). Analytical Biochemistry. 118(1): 113-9, Nov 1981
  • Yager TD, Reuben MA, Ainpour PR, Wickstrom E. Molecular rulers with 5 or 11 prolines intramolecularly crosslink to G45 of yeast phenylalanine tRNA. Febs Letters. 133(1): 59-62, Oct 1981
  • Wickstrom E. Physical parameters of Escherichia coli translational initiation factor 3 binding to poly(A). Febs Letters. 128(1): 154-6, Jun 1981
  • Reuben MA, Ainpour PR, Hester HL, Neveln VL, Wickstrom E. Synthesis and intramolecular crosslinking of chlorambucilyl (prolyl)n [3H]phenylalanyl-tRNAPhe (yeast), n = 0, 5, 11 and 15. Biochimica Et Biophysica Acta. 654(1): 11-25, Jun 1981
  • Wickstrom E, Behlen LS, Reuben MA, Ainpour PR. Molecular rulers for measuring RNA structure: sites of crosslinking in chlorambucilyl-phenylalanyl-tRNAPhe (yeast) and chlorambucilyl-pentadecaprolyl-phenylalanyl-tRNAPhe (yeast) intramolecularly crosslinked in aqueous solution. Proceedings of the National Academy of Sciences (USA). 78(4): 2082-5, Apr 1981
  • Wickstrom E, Parker KK, Hursh DA, Newton RL. Chlorambucil [3H]phenylalanyl-tRNA crosslinking to 50 S ribosomal subunit proteins L4, L26--27 and L18--20. Febs Letters. 123(2): 273-6, Jan 1981
  • Wickstrom E. Chlorambucil inhibition by dimethyl sulfoxide and thiosulfate: implications for chlorambucil chemotherapy. Medical Hypotheses. 6(10): 1035-41, Oct 1980
  • Schleich T, Wickstrom E, Twombly K, Schmidt B, Tyson RW. Circular dichroism study of Escherichia coli initiation factor 3 binding to nucleic acids. Biochemistry. 19(19): 4486-92, Sep 1980
  • Wickstrom E, Tyson RW, Newton G, Obert R, Williams EE. Stoichiometry of homopolynucleotide binding to Escherichia coli translational initiation factor 3. Archives of Biochemistry and Biophysics. 200(1): 296-300, Mar 1980
  • Ainpour PR, Wickstrom E. Modifications of solid phase peptide synthesis to obtain homogeneous oligoprolines in high yield. International Journal of Peptide and Protein Research. 15(3): 225-35, Mar 1980
  • Reuben MA, Kusnezov IJ, Wickstrom E. Inhibition of deacylation and improvement in N-hydroxysuccinimide ester modification of phenylalanyl-tRNA by dimethyl sulfoxide. Biochimica Et Biophysica Acta. 565(1): 219-23, Nov 1979
  • Wickstrom, E. Escherichia coli initiation factor IF3 binding to AUG and AUG-containing single strands and hairpin loops, and nonspecific binding to polymers. Biochimica et Biophysica Acta 349:125-130, Aug 1974
  • Wickstrom E, Tinoco I Jr. The stability of RNA hairpin loops containing A-U-G: An-U-G-Um. Biopolymers. 13(11): 2367-83, Nov 1974
  • Wickstrom E. Circular dichroism during deacylation of methionyl-tRNA met -f and formylmethionyl-tRNA met -f from E. coli. Biochemical and Biophysical Research Communications. 43(5): 976-83, Jun 1971

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