Dmitri Simberg, Ph.D. CURRICULUM VITAE A. Education 1998-2004 Ph. D. in Biochemistry, The Hebrew University of Jerusalem, Israel. Thesis: Cationic lipid-mediated transfection in vitro and in vivo: the main obstacles and means to overcome them. 1992-1996 B. Pharm., The Hebrew University of Jerusalem, Israel 1989-1991 2 nd Medical Institute, Moscow, Russian Federation B. Employment History 2013 Assistant Professor, Department of Pharmaceutical Sciences, The Skaggs School of Pharmacy, UC Denver 2013 Associate Project Scientist, UCSD 2008-2013 Assistant project scientist, NanoTumor Center, Moores Cancer Center, UCSD 2006-2007 Postdoctoral fellow, Laboratory of Prof. Robert Mattrey, Department of Radiology, UCSD. Research Theme: Perfluorocarbon-based molecular imaging reagents. 2004-2006 Postdoctoral fellow, Laboratory of Prof. Erkki Ruoslahti, Burnham Institute, La Jolla. Research Theme: Amplified targeting of nanoparticles for tumor imaging and treatment 2000-2004 Teaching assistant, Hebrew University of Jerusalem C. Grants 2013-2016 NIH R33: High quality CTC isolation using microbubbles for subcontract downstream molecular analysis 2012-2014 NIH R21 Photoassisted targeting of immunotherapy to the bladder 2012-2013 NIH R21 Non invasive detection of DNA biomarkers in pancreatic cancer 2010-2013 DoD (Army) breast cancer IDEA Engineered erythrocytes for prevention of metastatic dissemination of breast cancer 2009-2012 NIH R21 IMAT Program Isolation of CTCs from blood using microbubbles 2008-2009 UCSD ICMIC Developmental Award Ultrasound-Targeted Gene Delivery in B-Cell Malignancies. 1
D. Awards 2012 Nano Drug Delivery Symposium Best Poster (3 rd place) Award 2009 14 th International Drug Delivery Symposium s Best Poster Award, Salt Lake City, Utah 2007 Contrast Media Research Young Investigator Award, Banff, Canada 2002-2004 Hebrew University Rector s Excellence Scholarship for graduate students 2002 8 th Liposome Research Days conference s Best Poster Award, Berlin, Germany E. Service 2013 Reviewer, NIH Special Emphasis Study Section 2013 Reviewer, The Kentucky Science and Engineering Foundation (KSEF) 2013 Reviewer, The University of Missouri Research Board 2012 Member, Cancer Center Solid Tumor Therapeutics Program 2012 Reviewer, ACS seed grant committee 2013 Scientific Advisor Committee for the Journal of Pharmaceutical Sciences F. Peer reviewed publications In review/revision 1. Shi G, Mukthavaram R, Kesari S, Simberg D. Targeting and Depletion of Circulating Cells and Tumor Cells in Vivo Using Ligand-Painted Erythrocytes (Submitted). 2. Ortac I, Simberg D, Yang J, Trogler WC, Tsien RY, Esener S. Active enzyme loaded nano-wiffle-balls that avoid immune response and proteolysis (Submitted) 3. Miao-Ping Chien, Dmitri Simberg, Matthew P. Thompson, Tomoko Hayashi, Christine Gray, and Nathan C. Gianneschi. Programming Pharmacokinetics in Vivo via Remotely Controlled Switching of Nanoparticle Size and Shape (Second revision). Published 1. Shi G, Cui W, Mukthavaram R, Kesari S, Simberg D. (2013) Binding and isolation of tumor cells in biological media with perfluorocarbon microbubbles. Methods (In press). 2. Mukthavaram R, Jiang P, Saklecha R, Bharati I, Nomura N, Chao Y, Pastorino S, Pingle SC, Fogal V, Wrasidlo W, Majeti B, Simberg D, Makale M, Kesari S. (2013) Liposomal encapsulation of staurosporine reduces in vivo toxicity and enhances tumor response. Intl J of Nanomedicine (in press). 3. Shi G, Mukthavaram R, Kesari S, Simberg D. (2013) Distearoyl anchor-painted erythrocytes with prolonged ligand retention and circulation properties in vivo. Adv. Healthcare Mater (In press). 2
4. Chao Y, Karmali P, Mukthavaram R, Kesari S, Kouznetsova V, Tsigelny I, Simberg D. (2013). Direct recognition of superparamagnetic nanocrystals by macrophage scavenger receptor SR-AI. ACS Nano (in press). 5. Shi, G., Cui, W., Benchimol, M., Liu, Y.-T., Mattrey, R., Kesari, S., Esener, S.C., and Simberg, D. (2013). Isolation of rare tumor cells from blood cells with buoyant perfluorocarbon immuno-microbubbles. PLoS One (in press). 6. Chao Y, Makale M, Karmali P, Tsigelny I, Merkulov S, Ruoslahti E, Simberg D. Recognition of dextran-coated superparamagnetic iron oxide nanoparticles (Feridex) by charged domains of macrophage scavenger receptors. Bioconjugate Chemistry, 2012, 23 (5), 1003 1009. 7. Karmali P, Chao Y, Park J-H, Sailor M, Ruoslahti E, Esener S, Simberg D. Different effect of hydrogelation on anti-fouling and circulation properties of iron oxide nanoparticles. Mol Pharmaceutics, 2012, 9 (3), pp 539 545. 8. Karmali P, Chao Y, Merkulov S, Ruoslahti E, Simberg D. Role of carbohydrate (lectin) receptors in the macrophage uptake of dextran-coated iron oxide nanoparticles. Adv Exp Med Biol. 2012;733:115-23. 9. Ibsen S, Benchimol M, Simberg D, Esener S. Ultrasound mediated localized drug delivery. Adv Exp Med Biol. 2012;733:145-53. 10. Ibsen S, Benchimol M, Simberg D, Steiner J, Esener S. A novel nested liposome drug delivery vehicle capable of ultrasound triggered release of its payload. J. Control Release 2011: 155(3):358-66. 11. Simberg D, Zhang WM, Merkulov S, McCrae K, Park JH, Sailor MJ, Ruoslahti E. Contact activation of kallikrein-kinin system by superparamagnetic iron oxide nanoparticles in vitro and in vivo. J Control Release 2009: 140, 301-305. 12. Simberg D, Mattrey, R. Targeting of DNA-coated perfluorocarbon microbubbles to selective populations of circulating blood cells. J. Drug Targeting 2009: 17(5):392-8. 13. Simberg D, Park JH, Karmali PP, Zhang WM, Merkulov S, McCrae K, Sailor, MJ, Ruoslahti E. Differential proteomics analysis of the surface heterogeneity of dextran iron oxide nanoparticles and the implications for their in vivo clearance. Biomaterials 2009;30:3926-33. 14. Park Ji-Ho, von Maltzahn G., Zhang L, Derfus A, Simberg D, Harris T, Bhatia S, Ruoslahti E, Sailor MJ. Systematic surface engineering of magnetic nanoworms for in vivo tumor targeting. Small 2009, 5(6):694-700. 15. Simberg D, Duza T, Park J, Essler M, Pilch J, Zhang L, Derfus AM, Yang M, Hoffman RM, Bhatia S, Sailor MJ, Ruoslahti E. Self-amplifying homing of nanoparticles to tumors. PNAS 2007, 104(3):932-6. 16. Khazanov E, Simberg D (equal contribution), Barenholz Y. Lipoplexes prepared from cationic liposomes and mammalian DNA induce CpG-independent, direct cytotoxic effects in cell cultures and in mice. J. Gene Medicine, 2006, 8(8): 998-1007. 17. Joseph A, Itskovitz-Cooper N, Samira S, Flasterstein O, Eliyahu H, Simberg D, Goldwaser I, Barenholz Y, Kedar E. A new intranasal influenza vaccine based on a novel polycationic lipid-ceramide carbamoyl-spermine (CCS) I. Immunogenicity and efficacy studies in mice. Vaccine. 2006, 24(18): 3990-4006. 3
18. Simberg D, Weiss A, Barenholz Y. Reversible mode of binding of serum proteins to DOTAP/Cholesterol lipoplexes: a possible explanation for intravenous lipofection efficiency. Hum Gene Ther., 2005, 16(9):1087-96. 19. Simberg D, Weisman S, Talmon Y, Faerman A, Shoshani T, Barenholz Y.The role of organ vascularization and lipoplex serum initial contact in intravenous murine lipofection. J. Biol. Chem., 2003, 278(41): 39858-65. 20. Simberg D, Danino D, Talmon Y, Minsky A, Ferrari M, Wheeler CJ, Barenholz Y. Phase behavior, DNA ordering, and size instability of cationic lipoplexes: relevance to optimal transfection activity. J. Biol. Chem., 2001, 276(50): 47453-9. 21. Simberg D, Hirsch-Lerner D, Nissim R, Barenholz Y. Comparison of different commercially available, cationic lipid-based transfection kits. J. Liposome Res., 2000, 2000, 10: 1-13. E. Invited book chapters and reviews 1. Simberg D and Tsigelny I. Has the time for in silico design of nanomedicines finally arrived? Editorial in Nanomedicine and Biotherapeutic Discovery. 2. Karmali, PP. and Simberg D. Interactions of nanoparticles with plasma proteins: implication on clearance and toxicity of drug delivery systems. Expert Opinion Drug Delivery 2011 8(3): 343-357. Invited review. 3. Simberg D, Weisman S, Talmon Y, Barenholz Y. DOTAP (and other cationic lipids): chemistry, biophysics, and transfection. Critical Reviews Therapeutic Drug Carrier Syst., 2004, 21(4): 257-317. Invited review. 4. Simberg D, Hirsch-Lerner D, Zuidam N-J, Even-Chen S, Kerner M, Eliyahu H, Plis- Finarov A, Servel N, Weisman S, Talmon Y, Barenholz Y. Cationic lipid nucleic acid complexes (lipoplexes): from physicochemical properties to in vitro and in vivo transfection kits. NATO ASI Life Sciences, 2003, Chemical Probes in Biology. Book chapter. G. Posters and talks 1. 2013, Long-circulating targeted RBC platform for tumor therapy 2 nd Nanomedicine conference, Los Angeles (poster) 2. 2012, Mechanisms of recognition of iron oxide nanoparticles by macrophage scavenger receptors NanoDDS 12 Atlantic City (poster); 3. 2012, Development of engineered red blood cells as platform for tumor imaging and therapy, Gordon Research Conference, Waterville Valley NH (poster) 4. 2011, Isolation of circulating tumor cells with microbubbles, 11 th Annual Innovative Molecular Analysis Technologies (IMAT) meeting, Rockville, MS (oral presentation) 5. 2011, Engineered erythrocytes for prevention of metastatic cancer, Era of Hope Conference, Orlando (poster); 6. 2010, Mechanisms of immune recognition of nanoparticles, 47 th Oholo Conference, Eilat, Israel (oral presentation); 7. 2010, Mechanisms of Interactions of Iron Oxide Nanoparticles with Proteins and Immune Receptors, TechConnect World, Anaheim (oral presentation); 4
8. 2009, Microbubbles for isolation of tumor biomarkers presented at 10 th Annual Innovative Molecular Analysis Technologies (IMAT) meeting, Bethesda (poster); 9. 2009, Proteomics-assisted study of in vivo clearance of iron oxide nanoparticles presented at 14 th International Drug Delivery Symposium, Salt Lake City (poster); 10. 2007, Interactions between microbubbles and blood cells, presented at Contrast Media Research Conference, Banff, Canada (invited oral presentation); 11. 2006, Self-amplifying delivery of nanoparticles to tumor vasculature, International Conference on Biopharmaceutical Science and Technology, San Diego (invited oral presentation); 12. 2006, Role of serum proteins in the in vivo clearance of iron oxide nanoparticles, 1 st National Cancer Institute Alliance for Nanotechnology in Cancer Investigators Meeting, San Diego (poster); 13. 2004, Mechanisms of binding of serum proteins to cationic lipoplexes, 9 th Liposome Research Days Conference, Hsinchu, Taiwan (poster); 14. 2002, Phase behavior, DNA ordering, and size instability of cationic lipoplexes. Relevance to optimal transfection activity, 8 th Liposome Research Days Conference, Berlin, Germany (poster); 15. 2001, Use of fluorescent probes for studying intracellular fate of cationic lipid-dna complexes, presented at 7 th Conference on Methods and Applications of Fluorescence Amsterdam 2001 (poster); 16. 1999, DNA structure in lipoplexes: effect of lipid composition, 4 th International Conference on Liposome Advances, London (poster); 17. 1999, Oligonucleotide lipoplexes: Electrostatics, state of aggregation and intracellular distribution, NATO ASI workshop, Marathon, Greece (oral presentation). H. Other service (ad hoc reviewer) Angewandte Chemie Intl Edition, International Journal of Nanomedicine; Biomaterials; Journal of Controlled Release; Nanomedicine: Nanotechnology, Biology, and Medicine, Journal of Visualized Experiments, Expert Opinion in Drug Delivery, ACS Nano, Molecular Pharmaceutics, Bioconjugate Chemistry, ACS Applied Materials & Interfaces, Science Transl. Medicine. 5