Download biographical sketch - UNC Lineberger Comprehensive Cancer Center

BIOGRAPHICAL SKETCH
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NAME
POSITION TITLE
Alexander V. Kabanov
Professor, University of North Carolina Chapel-Hill
(UNC-Chapel Hill)
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
My laboratory has a long-standing interest and expertise in polymer-based systems for drug delivery of small
molecules and biopolymers for treatment of cancer and other diseases. I have contributed papers on block
copolymer micelles, polyplexes, and nanogels, characterizations of their interactions in cells, in vivo
biodistribution, targeted drug delivery, gene delivery, and treatment of tumors. My work on Pluronic block
copolymers in cancer chemotherapy led to the first-in-man clinical trial of polymeric micelle drug (SP1049C) in
treatment of cancer, with this drug demonstrating high activity in Phase II clinical trials against chemotherapyresistant advanced cancer of esophagus. We also reported recently that Pluronic facilitates DOXIL antitumor
effect in vivo by facilitating drug release from the liposomes within the tumor. This study provided foundation
for the present proposal in which we will collaborate with Dr. Zamboni and other members of our team to
optimize and validate the proposed approach in GEMMs of ovarian and breast cancer. This collaboration
emerged after I moved to UNC-Chapel Hill Iwhich was motivated by mu strong commitment fort further
translating the technologies to marketed pharmaceutical produsts. Prior to that I was founder and director of
the 32-faculty strong UNMC Center for Drug Delivery and Nanomedicine, and PI of NIH CoBRE grant and thus
have experience in leading complex, cross-disciplinary projects.
B. Positions and Honors
Positions and Employment
1987-1990
1988-1990
1990-1991
1991-1993
1991-1997
1994-2001
1995-2012
2001-2012
2001-2012
2002-Present
2004-2012
2004-2012
2005-2012
2007-2012
2008-2012
2008-2012
2012-Present
2012-Present
2012-Present
Research Fellow, Department of Chemical Enzymology, MSU, Moscow, USSR
Head, Laboratory of Biopolymers, Institute of Applied Molecular Biology, Moscow, USSR
Senior Research Fellow, Department of Chemical Enzymology, MSU
Head, Department of Biopolymers, National Research Center of Molecular Diagnostics and
Therapy (former Institute of Applied Molecular Biology), Moscow, Russia
Leading Research Fellow, Department of Chemical Enzymology, MSU
Associate Professor, College of Pharmacy, UNMC, Omaha, NE
Member, UNMC Eppley Cancer Center, Omaha, NE
Professor of Pharmaceutical Sciences, College of Pharmacy, UNMC
Professor (courtesy), Eppley Institute for Research in Cancer and Allied Diseases, UNMC
Professor (adjunct/visiting), Faculty of Chemistry, MSU
Parke-Davis Endowed Chair in Pharmaceutics, College of Pharmacy, UNMC
Director, Center for Drug Delivery and Nanomedicine (CDDN), UNMC
Professor (courtesy), Department of Genetics, Cell Biology and Anatomy, UNMC
Professor (courtesy), Pharmacology and Experimental Neuroscience, UNMC
Associate Director, Center for Clinical and Translational Research, UNMC
Director, NIH CoBRE Nebraska Center for Nanomedicine, UNMC
Mescal S. Ferguson Distinguished Professor, UNC Eshelman School of Pharmacy
Director, Center for Nanotechnology in Drug Delivery, UNC Eshelman School of Pharmacy
Co-Director, Carolina Institute for Nanomedicine, UNC-Chapel Hill
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; 1991 USSR Medal “For Valiant Labor”
(signed by President Mikhail Gorbachev); 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 award; 2009 UNMC Scientist Laureate; 2010 Russian “Megagrant”.
C. Selected Peer-Reviewed Publications (from 230 papers, over 12,000 citations; h-factor 61):
1. Alakhov VY, Moskaleva EY, Batrakova EV, Kabanov AV. Hypersensitization of multidrug resistant human
ovarian carcinoma cells by Pluronic P85 block copolymer. Bioconjug Chem 1996, 7(2):209-16. PMID: 8983343
2. Batrakova EV, Dorodnych TY, Klinskii EY, Kliushnenkova EN, Shemchukova OB, Arjakov SA, Alakhov
VY, Kabanov AV. Anthracycline antibiotics non-covalently incorporated into the block copolymer micelles: in
vivo evaluation of anti-cancer activity, Br J Cancer, 1996, 74 10):1545-52. PMCID: PMC2074856
3. Venne A, Li S, Mandeville R, Kabanov AV, Alakhov VY Hypersensitizing effect of pluronic L61 on
cytotoxic activity, transport, and subcellular distribution of doxorubicin in multiple drug-resistant cells, Cancer
Res, 1996, 56 (16): 3626-29. PMID: 8705995
4. Alakhov V, Klinsky E, Li S, Pietrzynski G, Venne A, Batrakova E, Bronich T, Kabanov A. Block
copolymer-based formulation of doxorubicin. From cell screen to clinical trials. Coll Surf B: Biointerfaces 1999
16:113-34.
5. Batrakova E, Lee S., Li S., Venne A., Alakhov V, Kabanov A. Fundamental relationships between the
composition of Pluronic block copolymers and their hypersensitization effect in MDR cancer cells. Pharm Res
1999, 16 (9):1373-9. PMID: 10496652
6. Batrakova EV, Li S, Elmquist WF, Miller DW, Alakhov VY, Kabanov AV. Mechanism of sensitization of
MDR cancer cells by Pluronic block copolymers: selective energy depletion, Br J Cancer, 2001, 85(12):198797. PMCID: PMC2364003
7. Batrakova EV, Li S, Li Y, Alakhov VY, Elmquist WF, Kabanov AV. Distribution kinetics of a micelleforming block copolymer pluronic P85. J. Control. Release, 2004, 100(3):389-97. PMID: 15567504
8. Minko T, Batrakova EV, Li S, Li Y, Pakunlu RI, Alakhov VY, Kabanov AV. Pluronic block copolymers alter
apoptotic signal transduction of doxorubicin in drug-resistant cancer cells, J. Control. Release, 2005,
105(3):269-78. PMCID: PMC2711210
9. Batrakova EV, Kelly DL, Li S, Li Y, Yang Z, Xiao L, Alakhova DY, Sherman S, Alakhov VY, Kabanov AV.
Alteration of genomic responses to doxorubicin and prevention of MDR in breast cancer cells by a polymer
excipient: pluronic P85. Mol Pharm, 2006, 3(2):113-23. PMCID: PMC2566789
10. Batrakova EV, Kabanov AV. Pluronic block copolymers: Evolution of drug delivery concept from inert
nanocarriers to biological response modifiers, J Control Release, 2008, 130(2):98-106. PMCID: PMC2678942
11. Sharma AK, Li Z, Li S, Kelly DL, Alakhov VY, Batrakova EB, Kabanov AV. Prevention of MDR
development in leukemia cells by micelle-forming polymeric surfactant. J. Control. Release, 2008, 131(3):2207. PMCID: PMC2711209
12. Alakhova DY, Rapoport NY, Batrakova EV, Timoshin AA, Li S, Nicholls D, Alakhov VY, Kabanov AV.
Differential metabolic responses to pluronic in MDR and non-MDR cells: A novel pathway for
chemosensitization of drug resistant cancers. J Control Release 2010, 142(1):89-100 PMCID: PMC3113470
13. Batrakova EV, Li S, Brynskikh AM, Sharma AK, Li Y, Boska M, Gong N, Mosley RL, Alakhov VY,
Gendelman HE, Kabanov AV. Effects of pluronic and doxorubicin on drug uptake, cellular metabolism,
apoptosis and tumor inhibition in animal models of MDR cancers, J Control Release, 2010, 143(3):290-301.
PMCID: PMC3089980
14. Nukolova NV, Oberoi HS, Kabanov AV, Bronich TK. Folate-decorated nanogels for targeted therapy of
ovarian cancer, Biomaterials 2011, 32(23):5417-26. PMCID: PMC3255291
15. Zhao Y, Alakhova DY, Kim JO, Bronich TK, Kabanov AV. A simple way to enhance Doxil therapy: Drug
release from liposomes at the tumor site by amphiphilic block copolymer, J Control Release, 2013, doi:pii:
S0168-3659(13)00123-5. 10.1016/j.jconrel.2013.02.026. PMID: 23474033.
D. Research Support
Ongoing Research Support
1U01 CA151806
Kabanov (PI)
09/02/2010 - 07/31/2015
High Capacity Nanocarriers for Cancer Chemotherapeutics
Role: PI
An innovative drug delivery platform is proposed to improve chemotherapy of cancer with these goals: 1)
optimize poly(2-oxazoline)s structures for water-insoluble drugs; 2) determine pharmacokinetics and maximum
tolerated doses; 3) validate anti-tumor activity in mouse models of breast cancer, and 4) develop targeted
micelles effective against Herceptin resistant tumors. This CNPP joins together pharmaceutical scientists and
cancer researchers who contribute to the Alliance for Cancer Nanotechnology through trans-alliance activities.
2R01 NS051334
Kabanov, Banks (co-PIs)
02/15/2006 - 03/31/2015
Polypeptide modification for enhanced brain delivery
Role: PI
This is a competing continuation of the R01 NS051335. The long-term goal is to produce polypeptides that
could cross the blood-brain barrier (BBB) and so be developed as central nervous system (CNS) therapeutics.
Analogs completing this development will be a) active in brain, b) have favorable pharmacokinetics, c) be able
to cross the BBB in obese mice, and d) reverse obesity after iv injection. Such analogs are candidates for
clinical trials in human obesity.
R01 CA89225
Kabanov (PI)
07/01/2001 - 04/30/2013
Interactions of Pluronic Block Copolymers in Drug Resistant Cancers
Role: PI (no-cost extension)
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.
W81XWH-09-1-0386
Kabanov (PI)*, Bronich (PI)**
07/01/2009 - 06/30/2013
Synthetic Nanovaccines Against Respiratory Pathogens (SYNARP)
Role: PI*, Co-I**
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.
11.G34.31.0004 (Rus. Ministry of Sci. and Education) Kabanov (PI)
11/10/2010 – 12/31/2014
Chemical Design of Bionanomaterials
Role: PI
This is a strategic infrastructure grant to MSU in Russia (no funds to US institution) from Rus. Ministry of Sci.
and Education to establish new laboratory at MSU to design and characterize novel bionanomaterials Dr.
Kabanov is the only chemist among first 40 winners of such award and serves as a visiting professor at MSU
(with the UNMC/UNC approvals and inter-institutional agreements). Research focuses on antioxidant,
antibacterial and pesticide-scavenging enzyme therapeutics and effects of magnetism in biochemistry.
1P20RR021937-01A2
Kabanov (PI)*, Bronich (PI)**
09/26/2008 – 06/30/2013
COBRE: Nebraska Center for Nanomedicine
Role: PI*, consultant**
COBRE main goal is to strengthen the biomedical research infrastructure at the institution through the
establishment of a thematic multi-disciplinary center and enhancing the ability of investigators in this center to
compete independently for complementary NIH individual research grants or other external peer-reviewed
support. This project develops an interdisciplinary Nanomedicine Center at UNMC focusing on polymer-based
delivery systems and nanotherapeutics for cancer, neurodegenerative and cardiovascular diseases.
W81XWH-10-1-0806
Mallapragada (PI)
09/01/2010 - 08/31/2013
Targeted Nanovaccine Platforms Against Respiratory Pathogens (TANARP)
Role: Co-PI*, consultant**
This project develops targeted vaccines against respiratory infections using pseudotyping technologies and
novel nanotechnology platforms based on safe and degradable adjuvant polymer systems that enhance
antigen presentation and stimulate immunity.
W81XWH-11-1-0700
Mallapragada (PI)
INNS: Integrated neuroprotective and neuroregenerative strategies,
This proposal develops cell-nanomedicine based therapeutics.
08/29/2011 - 08/28/2014
Role: Co-PI*, consultant**
* Until reallocation to UNC-Chapel Hill in July 2012.
** After reallocation to UNC-Chapel Hill in July 2012.
Completed Research Support (selected)
2 P30 MH062261-11
Fox (PI)
03/01/2011 - 02/29/2016
Chronic HIV Infection and Aging in NeuroAIDS (CHAIN) Center
Role: Co-I*
The CHAIN Center will research new ways to diagnose, predict, treat and prevent brain damage induced by
HIV via a systems biology approach.
1 P01 DA028555-01A1
Gendelman (PI)
07/15/2010 - 04/30/2013
NanoART Manufacture, Delivery and Pharmacokinetics for Drug Abusers
Role: Co-I*
This is an integrative cross approach translational and multi-investigator program grant seeking to develop
nanoformulated antiretroviral drug therapy from the bench to the patient.
R01 CA116591-04
Kabanov (PI)
05/1/06 – 04/30/12
Polymer based gene delivery
Role: PI
Co-administration of nonionic poly(ethylene oxide)-poly(propylene oxide) block copolymers (Pluronic) with
plasmid DNA has greatly increased the trangene expression of the 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.
R01 NS36229-09
Kabanov (PI)
09/15/97 - 06/30/09
Interactions of Block Copolymers in Blood Brain Barrier
Role: PI
The objective of this proposal is to enhance the brain delivery of small drugs across the BBB using Pluronic.
W81XWH-07-1-0218
Kabanov (PI)
04/01/07 - 03/31/11
Non-invasive nanodiagnostics of cancer (NINOC)
Role: PI
A platform nanotechnology was developed to deliver drugs and imaging agents to cancer cells. 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 cancer cells and provide site-specific delivery of the nanogels to tumors.
* Until reallocation to UNC-Chapel Hill in July 2012.
Additional information: 28 US patents awarded, over 100 patents worldwide.