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OMB No. 0925-0001/0002 (Rev. 08/12 Approved Through 8/31/2015)
BIOGRAPHICAL SKETCH
Provide the following information for the Senior/key personnel and other significant contributors.
Follow this format for each person. DO NOT EXCEED FOUR PAGES.
NAME
POSITION TITLE
Lee, Bong Seop
eRA COMMONS USER NAME (credential, e.g., agency login)
Faculty Research Scientist of Neurosurgery
LEEBONGSEOP
EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, include postdoctoral training and
residency training if applicable.)
DEGREE
INSTITUTION AND LOCATION
MM/YY
FIELD OF STUDY
(if applicable)
University of Technology, Darmstadt, Germany
B.S.
02/94
Chemistry
University of Technology, Darmstadt, Germany
M.S.
04/97
Chemistry
University of Regensburg, Germany
PhD
05/00
Biochemistry
University of Regensburg, Germany
Postdoc
04/02
Biochemistry
A. Personal Statement
I have an educational and professional background in organic synthetic chemistry and biochemistry that I
have further developed to polymer-/nanotechnology-based anti-cancer therapeutics. The goal of the
application of polymer technology/nanotechnology in my research is to evaluate the potentials of therapeutic
nanoparticles containing oxidation-responsive prodrug of camptothecin (CPT nanoprodrug), temozolomide,
paclitaxel and other chemos for the treatment of malignant neoplasms including gliomas, breast cancer,
panctreatic cancer, liver cancer, ovarian cancer, cervical cancer and metastatic cancers. Specifically, I have
been working on the development of the nanoprodrugs to target and eradicate radiation/ chemotherapy
resistant brain tumors and metastatic cancers. Given the lack of effective therapeutics for preventing and
treating metastatic cancers and brain tumors, a successful study would greatly accelerate the transitional
clinical development of this nanoplatform technology, which can be extended to other malignancies. In my PhD
and postdoctoral training at the University of Regensburg, Germany, I developed polymer-based drug delivery
systems Polycefin. In 2004, I joined the Department of Neurosurgery, Cedars-Sinai Medical Center and
successfully applied the system to the treatment of brain tumors. Since 2006, I have developed a novel
nanometer-sized drug/drug delivery system based on biodegradable prodrugs. This proprietary system, named
as nanoprodrug, is a versatile system which can be used as drug itself and as drug delivery system. Using the
nanoprodrug system containing biodegradable chemo prodrugs and/or imaging agents in the inner matrix with
secondary therapeutic/imaging agents attached on the surface of the nanoprodrug, would allow a
multifunctional construction of the anti-cancer nanoprodrug enabling multiple interventions for overcoming the
current limitations of conventional cancer treatments. I am PI of the nanotechnology-based development of
drug/drug delivery systems for the imaging and treatment of tumors and lead the nanomedicine group in the
lab, responsible for the research, coordination of collaborative work with other research labs in the CedarsSinai Medical Center, mentoring junior researchers, undergraduate and graduate students. My experience in
spear-heading research labs and projects and scientific expertise in chemistry, physics, biology,
nanotechnology and anticancer drug development allow me to serve as PI in a multidisciplinary cancer
research projects.
B. Positions and Honors
Positions and Employment
2000-2002
Post-doctoral Researcher, Department of Biochemistry, University of Regensburg, Regensburg,
Germany
2002-2004
Research Scientist, Department of Biochemistry, University of Regensburg, Regensburg, Germany
2005Research Scientist, Maxine Duntz Neurosurgical Institute, Department of Neurosurgery,
Cedars-Sinai Medical Center, Los Angeles, CA.
Other Experience and Professional Memberships
Member, American Association for Cancer Research
Member, Controlled Release Society
Member, European Federation of Biotechnology
US Patents
Patents Awarded:
1. Patent No.: 8,318,795
Date issued: November 27, 2012
Inventors: Yu, Lee
Antioxidant polymers containing [1,2]-dithiolane moieties and uses thereof
2. Patent No.: 8,603,531
Date issued: October 4, 2013
Inventors: Yu, Lee
Nanometer-sized prodrugs of NSAIDs
3. Notice of Allowance
Date issued: October 4, 2013
Inventors: Yu, Lee
Antioxidant camptothecin derivatives and antioxidant antineoplastic nanospheres thereof
4. Patent No.: 8,603,531
Date issued: October 4, 2013
Inventors: Yu, Lee
Nanometer-sized prodrugs of NSAIDs
5. Notice of Allowance (Japan)
Date issued: June 4, 2014
Inventors: Yu, Lee
Antioxidant camptothecin derivatives and antioxidant antineoplastic nanospheres thereof
6. Patent No.: 9,028,874
Date issued: May 12, 2015
Inventors: Yu, Lee
Antioxidant nanosphere comprising [1,2]-dithiolane moieties
Patents Pending:
1. Antioxidant, neuroprotective and antineoplastic nanoparticles comprising a therapeutic agent on an
amphiphilic spacer or an amphiphilic polymer
2. Neuroprotective nanoparticles for ischemia
3. Antioxidant, anti-inflammatory and anticancer derivatives of triptolide and nanospheres thereof
4. Reactive oxygen species-activated nanoprodrug of ibuprofen for targeting traumatic brain injury in mice
C. Selected Peer-reviewed Publications
1. Lee, B. S., Amano, T., Wang, H., Pantoja, J. L., Yoon, C. W., Hanson, C. J., Amatya, R., Yen, A., Black,
K.L., Yu, J.S. Reactive Oxygen Species Sensitive Nanoprodrug of Camptothecin to Treat Intracranial
Glioblastoma. ACS Nano, 7, 3061–3077, 2013.
2. Clond, M. A., Lee, B. S, Yu, J., Singer, M., Amano, T., Lamb, A. W., Drazin, D., Kateb B., Ley, E. J., Yu, J.
S. Reactive oxygen species-activated nanoprodrug of ibuprofen for targeting traumatic brain injury in mice.
PLoS ONE 8(4): e61819. doi:10.1371/journal.pone.0061819, 2013.
3. Lee, B. S., Yoon, C. W., Osipov, O., Moghavem, N., Nwachokor, D., Amatya, R., Na, R., Pantoja, J. L.,
Pham, M. D., Black, K. L. and Yu, J. S. Nanoprodrugs of NSAIDs: Preparation and Characterization of
Flufenamic Acid Nanoprodrugs. J. Drug Delivery. 2011.
4. Lee, B. S., Nalla, A. K., Stock, I. R., Shear, T. C., Black, K. L. and Yu, J. S. Oxidative stimuli-responsive
nanoprodrug of camptothecin kills glioblastoma cells. Bioorganic & Medicinal Chemistry Letters 20, 5262–
5268, 2010.
5. Lee, B. S., Yuan, X., Xu, Q., Ko, M., Nalla, A. K., Frankiel, I., Shear, T., Black, K. L. and Yu, J. S.
Nanoprodrugs of NSAIDs Inhibit the Growth of U87-MG Glioma Cell. J. Nanomaterials, 2010
6. Lee, B. S., Yuan, X., Xu, Q., McLafferty, F. S., Petersen, B. A., Collette, J. C., Black, K. L. and Yu, J. S.
Stimuli-responsive antioxidant nanoprodrugs of NSAIDs. Int. J. Pharm. 372, 112–124, 2009.
7. Lee, B. S., Yuan, X., Xu, Q., McLafferty, F. S., Petersen, B. A., Collette, J. C., Black, K. L. and Yu, J. S.
Preparation and characterization of antioxidant nanospheres from multiple α-lipoic acid-containing
compounds. Bioorg. Med. Chem. Lett. 19, 1678–1681, 2009.
8. Xu, Q., Yuan, X., Xu, M., McLafferty, F., Hu, J., Lee, B.S., Liu, G., Zhaohui, Z., Black, K.L. and Yu, J.S.
Chemokine CXC receptor 4–mediated glioma tumor tracking by bone marrow–derived neural
progenitor/stem cells. Mol. Cancer. Ther. 8, 2746–2753, 2009.
9. Ljubimova, J. Y., Fujita, M., Khazenzon, N. M., Lee, B. S., Wachsmann-Hogiu, S., Farkas, D. L., Black, K.
L. and Holler, E. Nanoconjugate based on polymalic acid for tumor targeting. Chem. Biol. Interact. 171,
195-203, 2008.
10. Fujita, M., Lee, B. S., Khazenzon, N. M., Penichet, M. L., Wawrowsky, K. A., Patil, R. , Ding, H., Holler, E.,
Black, K. L. and Ljubimova, J. Y. Brain tumor tandem targeting using a combination of monoclonal
antibodies attached to biopoly(beta-L-malic acid). J. Control. Release. 122, 356-63, 2007.
11. Fujita, M., Khazenzon, N. M., Lee, B. S., Holler, E., Black, K. L. and Ljubimova, J. Y. Development of
nanoconjugate with different monoclonal antibodies to inhibit molecular targets important for tumor
angiogenesis. NSTI-Nanotech, Vol.2, 760-762, 2007.
12. Lee, B. S., Fujita, M., Khazenzon, N. M., Wawrowsky, K. A., Wachsmann-Hogiu, S., Farkas, D. L., Black,
K. L., Ljubimova, J. Y., Holler, E. Polycefin, a new prototype of a multifunctional nanoconjugate based on
poly(beta-L-malic acid) for drug delivery. Bioconjug. Chem. 17, 317-26, 2006.
13. Fujita, M., Khazenzon, N. M., Ljubimov, A. V., Lee, B. S., Virtanen, I., Holler, E., Black, K. L. and
Ljubimova, J. Y. Inhibition of laminin-8 in vivo using a novel poly(malic acid)-based carrier reduces glioma
angiogenesis. Angiogenesis 9, 183-191, 2006.
14. Ljubimova, J. Y., Fujita, M., Lee, B. S., Khazenzon, N. M., Wachsmann-Hogiu, S., Farkas, D. L., Black, K.
L. and Holler, E. Nanoconjugate of poly(malic acid) with functional modules for drug delivery. NSTINanotech, Vol.2, 354-357, 2006.
15. Pinchai, N., Lee, B. S. and Holler, E. Stage specific expression of poly(malic acid) affiliated genes in the life
cycle of Physarum polycephalum Spherulin 3b and polymalatase. FEBS Journal 273, 1046-1055, 2006.
16. Holler, E. and Lee, B. S. Analysis of poly(-L-malic acid) in tissue and solution. Recent Res Devel Anal
Chem. 2, 177-192, 2002.
17. Doerhoefer, S., Windisch, C., Angerer, B., Lavrik, O., Lee, B. S. and Holler, E. The DNA-polymerase
inhibition activity of poly(-L-malic acid) in nuclear extract during the cell cycle of Physarum polycephalum.
Eur J Biochem 269, 1253-1258, 2002.
18. Lee, B. B. and Holler, E. -Poly(L-malate) production by non-growing microplasmodia of Physarum
polycephaum: Effect of metabolic intermediates and inhibitors. FEMS Microbiol Lett 193, 69-74, 2000.
19. Lee, B. S. and E. Holler. Effects of culture conditions on -poly(L-malate) production by Physarum
polycephalum. Appl Microbiol Biotechnol 51, 647-652, 1999.
20. Lee, B. S., Maurer, T., Kalbitzer, H. R. and Holler, E. -Poly(L-malate) production by Physarum
polycephalum: 13C Nuclear magnetic resonance studies. Appl Microbiol Biotechnol 52, 415-420, 1999.
21. Willibald, B., Bildl, W., Lee, B. S. and Holler, E. Is -poly(L-malate) synthesis catalysed by a combination of
-L-malyl-AMP-ligase and -poly(L-malate) polymerase? Eur J Biochem 265, 1085-1090, 1999.
D. Research Support
FasterCures: Milken Foundation
Principal Investigator:
Title of the Project:
Dates of Approved Project:
Yu, John
Dendritic Cell Based Immunotherapy
7/1/2012 – 6/30/2016
The goal of this project is to develop dendritic cell- based immunotherapeutics to treat brain tumors by
targeting CD133 overexpressing glioma stem cells.
Musella Foundation for Brain Tumor Research
Principal Investigator:
Lee, Bong Seop
Title of the Project:
Targeted Brain tumor Treatment using TQM-CPT Nanoprodrug
Dates of Approved Project:
1/1/2014 – 12/31/2014
The goal of this project is to develop a nanoprodrug system to image and treat brain tumors via targeting
tumor-specific molecular marker IL13 Receptor α2.
NanoGB13
Principal Investigator:
Title of the Project:
Dates of Approved Project:
Lee, Bong Seop
GB-13 conjugation to nanoparticle surface to increase cell
specificity
6/15/2013 – 11/26/2014
The goal of this project is to develop a nanoprodrug system to image and treat brain tumors using IL13
derivatives as brain tumor targeting ligand modification.