exw114

Eric Wickstrom, PhD

Contact Dr. Wickstrom

233 South 10th Street
209 & 219 Bluemle Life Sciences Building
Philadelphia, PA 19107-5541

(215) 955-4578
(215) 955-4580 fax

Medical School

PhD, Chemistry, University of California, Berkeley - 1972

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.

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