BIOGRAPHICAL SKETCH
Provide the following information for the key personnel and other significant contributors in the order listed on Form Page 2.
Follow this format for each person. DO NOT EXCEED FOUR PAGES.
NAME
POSITION TITLE
Alexander V. Kabanov
Professor, University of Nebraska Medical Center
(UNMC)
eRA COMMONS USER NAME
KABANOV.ALEXANDER
EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, and include postdoctoral training.)
DEGREE
(if applicable)
YEAR(s)
Faculty of Chemistry, Moscow State University
(MSU), Russia
M.S.
1979-1984
Chemistry
Department of Chemical Enzymology, MSU, Russia
Ph.D.
1984-1987
Chemical Kinetics and
Catalysis
INSTITUTION AND LOCATION
FIELD OF STUDY
A. Personal Statement
Dr. Kabanov is the Director of the Center for Drug Delivery and Nanomedicine (CDDN) and CoBRE Nebraska
Center of Nanomedicine. He is an expert in drug delivery and was among the first to develop polymer micelles
and polyion complexes for this purpose in late 80’s. His work using Pluronic block copolymers to overcome
MDR in cancer has led to the first Phase I and Phase II clinical trials of polymer micelle doxorubicin, SP1049C,
in cancer patients. He has been a co-founder of several companies including Supratek Pharma Inc. (Montreal,
Canada) that develops SP1049C. He is an Associate Director of the UNMC Center for Clinical and
Translational Research where he is responsible for novel methodologies and translational technologies key
function areas. He has published 200 scientific papers, was named a co-inventor on 26 US patents and
organized numerous scientific meetings, including a Gordon Research Conference (GRC) on Drug Carriers in
Medicine and Biology in 2006 and International Nanomedicine and Drug Delivery Symposium (NanoDDS)
series (www.nanoodds.org), held annually since 2003-. In 2006-2008 he chaired the “Biomaterials and
Biointerfaces” study section. Dr. Kabanov has scientific vision and experience to lead complex, crossdisciplinary projects in nanomedicine and drug delivery in cancer. He is currently supported by six grants by
National Institutes of Health and Department of Defense including two National Cancer Institute grants to
investigate block copolymer-based chemotherapeutic formulations for treatment of drug resistant cancers and
develop polymer-based DNA vaccination therapeutics for malignant melanoma.
B. Positions and Honors
Positions and Employment
1987-1990
Research Fellow, Department of Chemical Enzymology, MSU, Moscow, USSR
1988-1990
Head, Laboratory of Biopolymers, Institute of Applied Molecular Biology, Moscow, USSR
1990-1991
Senior Research Fellow, Department of Chemical Enzymology, MSU
1991-1993
Head, Department of Biopolymers, National Research Center of Molecular Diagnostics and
Therapy (former Institute of Applied Molecular Biology), Moscow, Russia
1991-1997
Leading Research Fellow, Department of Chemical Enzymology, MSU
1994-2001
Associate Professor, College of Pharmacy, UNMC, Omaha, NE
1995-Present Member, UNMC Eppley Cancer Center, Omaha, NE
2001-Present Professor of Pharmaceutical Sciences, College of Pharmacy, UNMC
2001-Present Professor (courtesy), Eppley Institute for Research in Cancer and Allied Diseases, UNMC
2002-Present Professor (adjunct), Faculty of Chemistry, MSU
2004-Present Parke-Davis Endowed Chair in Pharmaceutics, College of Pharmacy, UNMC
2004-Present Director, Center for Drug Delivery and Nanomedicine (CDDN), UNMC
2005-Present Professor (courtesy), Department of Genetics, Cell Biology and Anatomy, UNMC
2007-Present Professor (courtesy), Pharmacology and Experimental Neuroscience, UNMC
Other Experience and Professional Memberships
2003-06 (elected) member Board of Scientific Advisors for Controlled Release Society (CRS); 2007 Bioactive
Materials Program Chair for 34th CRS Annual Meeting; 2003-2006 member, Non-viral Gene Transfer Vectors
Committee for American Society of Gene Therapy; 2006, Co-Chair, Gordon Research Conference “Drug
Carriers in Biology and Medicine”; 1995- co-founder, Board of Directors, Chair, Scientific Advisory Board,
Supratek Pharma, Inc., Montreal, Canada; 2005- co-founder and member, Board of Directors, CSO,
InnovaForm Technologies, LLC, Philadelphia, PA; Editorial Boards: 1997- J. Contr. Release; 1998- J. Bioact.
Comp. Polymers; Editorial Advisory Boards: 1999- The AAPS J. (previously PharmSci); 2000- Adv. Drug Del.
Rev.; 2001- Bioconj. Chem.; 2003- J. Pharm. Sci.; 2005- Int. J. Nanomedicine; 2006- Section Editor, Drug
Delivery and Developmental Therapeutics J. Neuroimmune Pharmacol. Grants review: 1995- NSF, Petroleum
Research Fund, European Science Foundation, Israel Science Foundation, Australian Research Council,
Canada Foundation for Innovation and other agencies; 1999-2003 panels for CAREER awards, NSF Divisions
of Biotechnology/Biochemical Engineering and Material Research/Polymers; 1998-2004 (ad hoc) National
Institutes of Health (NIH) panels Hematology-1 (SBIR/STTR), Research Resources (P41, U-19), Drug Delivery
(chair); 2006-08 chair (2003-06 member) NIH Biomaterials and Biointerfaces study section), 2010 NCI Special
Emphasis Panel for NCI Centers of Cancer Nanotechnology Excellence I.
Honors
1988 Lenin Komsomol Prize; 1990 Doctor of Sciences (Chemistry and Biochemistry), MSU; 1995 National
Science Foundation (NSF) CAREER award; 2003 NSF Special Creativity Award; 2006 UNMC Distinguished
Scientist; 2007 University of Nebraska Outstanding Research and Creative Activity (ORCA) award; 2009
UNMC Scientist Laureate
C. Selected Peer-Reviewed Publications (Selected from 200 peer-reviewed publications):
Most relevant to the current application
1. Minko, T., Batrakova, E.V., Li, S., Li, Y., Pakunlu, R.I., Alakhov, V.Y., Kabanov, A.V. (2005) Pluronic block
copolymers alter apoptotic signal transduction of doxorubicin in drug-resistant cancer cells, J. Control.
Release 105(3):269-78.
2. Batrakova, E.V., Kabanov, A.V. (2008) Pluronic block copolymers: Evolution of drug delivery concept from
inert nanocarriers to biological response modifiers, J. Control. Release, 130(2):98-106. Epub 2008 Apr 24.
PMCID: PMC2678942
3. Alakhova, D.Y., Rapoport, N.Y., Batrakova, E.V., Timoshin, A.A., Li, S., Nicholls, D., Alakhov, V.Y.,
Kabanov, A.V. (2010) Differential metabolic responses to pluronic in MDR and non-MDR cells: A novel
pathway for chemosensitization of drug resistant cancers. J. Control. Release 142(1):89-100 Epub 2009
Oct 6. NIHMSID # 156599
4. Batrakova, E.V., Li, S., Brynskikh, A.M., Sharma, A.K., Li, Y., Boska, M., Gong, N., Mosley, R.L., Alakhov,
V.Y., Gendelman, H.E., Kabanov, A.V. (2010) Effects of Pluronic and Doxorubicin on drug uptake, cellular
metabolism, apoptosis and tumor inhibition in animal models of MDR cancers, J. Control. Release. Epub
2010 Jan 13. NIHMSID # 181167
5. Sahay, G., Kim, J.O., Kabanov, A.V., Bronich T.K. (2010) The exploitation of differential endocytic
pathways in normal and tumor cells in the selective targeting of nanoparticulate chemotherapeutic agents.
Biomaterials 31(5), 923-33. Epub 2009 Oct 22. NIHMSID # 151102
Additional recent publications of importance to the field (in chronological order)
6. Bronich, T.K., Keifer, P.A., Shlyakhtenko, L.S., Kabanov, A.V (2005) Polymer micelle with cross-linked
ionic core. J. Am. Chem. Soc. 127(23):8236-7.
7. Batrakova, E.V., Kelly, D.L., Li, S., Li, Y., Yang, Z., Xiao, L., Alakhova, D.Y., Sherman, S., Alakhov, V.Y.,
Kabanov, A.V. (2006) Alteration of genomic responses to doxorubicin and prevention of MDR in breast
cancer cells by a polymer excipient: pluronic P85. Mol. Pharm. 3(2):113-23.
8. Kabanov, A.V., Gendelman, H.E. (2007) Nanomedicine in the diagnosis and therapy of neurodegenerative
disorders, Progr. Polym. Sci. 32(8-9):1054-82. NIHMSID # 109893
9. Sahay, G, Batrakova, E.V., Kabanov, A.V. (2008) Different internalization pathways of polymeric micelles
and unimers and their effects on vesicular transport. Bioconjug. Chem., 19(10):2023-9. PMCID:
PMC2575076
10. Sharma, A.K., Zhang, Li., Li, S., Kelly, D.L., Alakhov, V.Yu., Batrakova, E.B., Kabanov, A.V. (2008)
Prevention of MDR development in leukemia cells by micelle-forming polymeric surfactant. J. Control.
Release, 131(3):220-7. PMCID: PMC2711209
11. Wang, F., Bronich, T.K., Kabanov, A.V., Rauh, R.D., Roovers, J. (2008) Synthesis and characterization of
star poly(epsilon-caprolactone)-b-poly(ethylene glycol) and poly(L-lactide)-b-poly(ethylene glycol)
copolymers: evaluation as drug delivery carriers. Bioconjug. Chem. 19(7):1423-9. Epub 2008 Jun 20.
PMCID: PMC2711207
12. Yang, Z., Sahay, G., Sriadibhatla, S., Kabanov, A.V. (2008) Amphiphilic block copolymers enhance cellular
uptake and nuclear entry of polyplex-delivered DNA. Bioconjug. Chem., 19(10):1987-94. PMCID:
PMC2574534
13. Gaymalov, Z.Z, Yang, Z, Pisarev, V.M., Alakhov, V.Yu., Kabanov, A.V. (2009) The effect of the nonionic
block copolymer pluronic P85 on gene expression in mouse muscle and antigen-presenting cells,
Biomaterials, 30 (6): 1232-45. Epub 2008 Dec 6. PMCID: PMC2667955
14. Kabanov, A.V., Vinogradov, S.V. (2009) Nanogels as pharmaceutical carriers: Finite networks of infinite
capabilities. Angew. Chem. Int. Ed. Engl. Jun 27;48(30):5418-5429. NIHMSID # 149084
15. Sahay, G., Gautam, V., Luxenhofer, R., Kabanov, A.V. (2010) The utilization of pathogen-like cellular
trafficking by single chain block copolymer. Biomaterials 31(7):1757-64. Epub 2009 Dec 5. NIHMSID #
164497
D. Research Support
Ongoing Research Support
COBRE: “Nebraska Center for Nanomedicine”
Principal Investigator: A.V. Kabanov
Agency: NIH
Type: 1P20RR021937-01A2
Period: 09/26/08 – 06/30/13
This proposal seeks to develop an interdisciplinary Nanomedicine Center at the University of Nebraska
Medical Center (UNMC). We have assembled a team of scientists with specific expertise in nanomedicine,
drug delivery, therapeutics and diagnostics. These will now be joined by biochemists, pharmacologists,
immunologists and neuroscientists. All will work, with singular focus, to develop the means to best use devices
of nanoscale size to improve outcomes for cancer, neurodegenerative and cardiovascular diseases. Such
approaches will deliver drugs to focal areas of central nervous system disease or directly to tumors. Parallel
studies seek nanotechnologies to improve diagnostic measures and disease monitoring. Within the Center up
to five junior project leaders are provided with research funds, experienced mentoring, and support of
Bioimaging and Nanomaterial core facilities. The Center also supports recruitment of faculty to UNMC working
in the Nanomedicine field. The long-term goals are to build upon and integrate already strong areas of
research in cancer biology, neurodegenerative disorders, molecular imaging (magnetic resonance and single
photon emission computed tomography) with material and pharmaceutical sciences (nanomaterials, polymers,
drug delivery, and gene delivery). The envisioned cross-disciplinary expertise could be joined between
traditional biomedical research and material sciences through the Center. There is no overlap with any of Dr.
Kabanov’s research projects.
“Polymer based gene delivery”
Principal Investigator: A.V. Kabanov
Agency: NIH NCI
Type: R01 CA116591-04
Period: 5/1/06 – 4/30/11
Co-administration of nonionic poly (ethylene oxide)-poly(propylene oxide) block copolymers (Pluronic) has
greatly increased the trangene expression of the plasmid DNA in the muscle. These block coplymers were
shown to be safe in human clinical trials for cancer chemotheray, which supports their evaluation for possible
use in gene therapy. The objectives of the proposal are 1) to determine most efficient Pluronic compositions for
plasmid DNA delivery in the muscle, 2) to determine the mechanism by which Pluronic enhances transgene
expression, and 3) to evaluate this system for delivery of DNA vaccines targeting malignant melanoma.
"Polypeptide modification for enhanced brain delivery"
Principal Investigator: A.V. Kabanov
Agency: NIH NINDS
Type: RO1 NS051335-03
Period: 2/15/06 - 1/30/10 (no cost)
Competitive renewal is being awarded
The objective of this proposal is to enhance delivery of leptin to the brain to control obesity. The aims (1) use
horseradish peroxidase (HRP) as a model to optimize the covalent modifications of polypeptides with fatty
acids and block copolymers to increase protein permeability across the blood brain barrier (BBB); (2)
determine the mechanism by which these modifications enhance BBB permeability; (3) determine in vivo the
extent of the accumulation by brain of modified HRP and leptin; (4) determine the extent to which modified
leptins retain biological activity after both peripheral administration and direct injection into brain.
"Interactions of Pluronic Block Copolymers in Drug Resistant Cancers"
Principal Investigator: A.V. Kabanov
Agency: NIH NCI
Type: RO1 CA89225-07
Period: 7/01/01-4/30/12
The objective of this proposal is to determine the mechanisms through which Pluronic sensitizes the drug
resistant cancer cells. The aims (1) characterize the effects of Pluronic on ATP levels in resistant and sensitive
cells; (2) identify drug/Pluronic formulations effective against resistant cancers; (3) determine whether the
effects of Pluronic on the energy state of the cell inhibit the functional activity of specific drug resistance
mechanisms; and (4) determine factors important for the efficient delivery of Pluronic to the tumor cells in vivo.
“Non-invasive nanodiagnostics of cancer (NINOC)”
Principal Investigator: A.V. Kabanov
Agency: DoD
Type: USAMRMC 06108004
Period: 4/01/07-04/30/11 (no cost)
This project will develop a platform nanotechnology to deliver imaging and diagnostic agents to the cancer
cells. The hydrophilic polymer nanogels of core-shell morphology are designed to entrap different types of
probes used in SPECT, CT, MR or luminescence detection. The surface of the nanogels is modified with
genetically engineered antibody fragments to target the surface of cancer cells and provide site-specific
delivery of the nanogels to tumors in the body.
“Synthetic Nanovaccines Against Respiratory Pathogens (SYNARP)”
Principal Investigator: A.V. Kabanov
Agency: DoD
Type: W81XWH-09-1-0386
Period: 7/01/09-06/30/13
The overall goal of this proposal is to develop fully synthetic vaccines against respiratory infections using novel
nanotechnology platforms based on safe and degradable adjuvant polymer systems that enhance antigen
presentation and stimulate immunity. The proposal focuses on achieving the following specific technical
objectives: 1) Develop molecular methods for intervention strategies employing novel synthetic nanovaccine
platforms encapsulating DNA and protein/peptide antigens that elicit immune response against influenza
H5N1; 2) Test the efficacy of nanovaccines-based intervention regimens against influenza H5N1 in animal
models.
Completed Research Support
"Interactions of Block Copolymers in Blood Brain Barrier"
Principal Investigator: A.V. Kabanov
Agency: NIH NINDS
Type: RO1 NS36229-09
Period: 9/15/97 - 6/30/09
The objective of this proposal is to enhance the brain delivery of drugs across the BBB using Pluronic. Using
brain microvessel endothelial cells as an in vitro model of the BBB, and using in vivo tissue sampling in mice,
the aims (1) characterize the mechanism of Pgp inhibition in BBB; (2) examine the extent to which Pluronic
effects can alter other carrier systems in BBB; (3) Examine the extent to which Pluronic can alter vesicular
transport in BBB and, (4) determine how Pluronic affects delivery of drugs to the brain in vivo.
"Structure and Dynamics of Block Ionomer Complexes”
Principal Investigator: A.V. Kabanov
Agency: NSF
Type: DMR-0513699
Period: 6/01/05-5/31/09
The major goal of this project is to explore dispersed composite nanomaterials which represent 1) micelle-like
aggregates with the polyion complex core and hydrophilic; 2) micelles with a hydrophobic cores and polyion
complex corona. The work focuses on the reactions of polyelectrolyte interchange involving these materials
and utilizes variety of experimental and theoretical approaches to determine the rates of these reactions and
understand the contribution of the core-shell architecture to the dynamic properties of these materials.
Additional information: 26 US patents awarded.