LEONID DZANTIEV, Ph.D.
PROFILE
Research scientist with extensive training in protein biochemistry, molecular
biology, bioanalytical chemistry, and assay development. 15 years of scientific
experience in both academia and industry. Dedicated, goal-directed researcher,
team player with proven ability to meet deadlines, strong interpersonal skills,
and excellent communication abilities.
SCIENTIFIC EXPERTISE
• Protein expression, purification, and recovery
• Target validation, compound screening in search for druggable targets
• Enzymatic- and immuno- assay development
• Bio-analytical techniques
• Molecular biology
• Nuclear receptor biochemistry, DNA enzymology, DNA polymerase mechanism
• Scientific translation and editing
PROFESSIONAL EXPERIENCE
Integrated Oncology Solutions, Inc. RTP, NC 03/2008-current
Senior Protein Biochemist
Expression and purification of human nuclear receptors
Company’s protein biochemistry expert
• optimized baculovirus-based expression, purification, and scale-up
procedures for rapid production of highly purified active protein targets to
support all company research activities
• developed and optimized an ELISA-based activity assay for functional
validation and QC of protein targets
• optimized and conducted high-throughput T7 phage display screens for
protein-protein interactions
• functioned as a kew team member in a dynamic, fast-paced environment of a
small biotech company focused on discovering novel nuclear receptor modulators
Duke University Medical Center, Durham, NC 2001-2008
Research Associate, Senior Research Associate
Enzymatic reconstitution of a human DNA repair pathway (Dr. Paul Modrich, PI):
• developed and optimized enzymatic assays for DNA metabolic activities,
including protein-DNA interactions, exo- and endonucleolytic DNA degradation, DNA
synthesis, etc.
• aquired an expertise in protein expression and purification
• reconstituted and analyzed a complex in vitro protein system that is capable
of bidirectional excision and re-synthesis of mismatched DNA
• identified and purified Replication Factor C as a new activity required for
mismatch repair
• demonstrated involvement of DNA polymerase in reconstituted human
mismatch repair
• purified activities involved in human mismatch repair from over-expression
systems
• constructed phage f1-based DNA substrates for the mismatch repair reaction
• obtained human cell extracts and characterized their proficiency in DNA
repair and DNA synthesis
• trained laboratory personnel in DNA enzymology
Department of Chemistry, Wayne State University, Detroit, MI 1995-2001
Graduate Research Assistant, Biochemistry
Graduate Teaching Assistant, General Chemistry
Ph.D. dissertation: “Mechanism of Enzymatic DNA Synthesis and Its Inhibition
by Carcinogenic DNA Adducts” (Dr. Louis J. Romano, Advisor)
• performed large scale synthesis, HPLC and gel purification, and
characterization of DNA oligonucleotides containing site-specific
N-2-acetylamimofluorene and N-2-aminofluorene adducts for biochemical and
crystallographic studies
• developed a technique for detection of conformational changes in the DNA
polymerase structure
• developed an assay to measure dissociation constants for interaction of a
DNA polymerase with DNA in the presence of nucleotides
• demonstrated that bulky carcinogenic DNA adducts alter conformational
transitions and DNA binding properties of a DNA polymerase
• investigated significance of nucleotide hydrogen bonding vs. geometric shape
for DNA polymerase activity
• gave talks at two major AACR conferences
Center for Medical Biotechnology, Institute of Gene Biology, 1991-1995
Institute of Biochemistry, Moscow, Russia
Research Assistant
Diploma thesis: “Detection of Human Cytomegalovirus Using PCR”
• Monoclonal antibody production (including abzymes)
• immunochemical methods for detection of various antigens and haptens
• PCR-based methods for detection of viral pathogens in biological samples
EDUCATION
Ph.D., Biochemistry 1995-2001 WAYNE STATE UNIVERSITY, Detroit,
MI
B.S/M.S., Chemistry/Biotechnology 1988-1994
UNIVERSITY OF CHEMICAL ENGENEERING, Moscow, Russia,
PROFESSIONAL TRAINING
NCRAF Regulatory Affairs Certification (US) Workshop 2007
GLP, GMP, GCP.
TECHNICAL SKILLS
BIOANALYTICAL: FPLC (ACTA, WATERS), HPLC, ELISA, PCR, preparation of biological
samples for analysis
ENZYMOLOGY: enzyme kinetics, protein-protein and protein-DNA interactions,
dissociation constant determination, multiple types of enzymatic assays, assay
development
PROTEIN BIOCHEMISTRY: protein purification from human cells, plasma, bacterial
and baculovirus expression systems, protein expression and overproduction in
bacterial and insect cells, activity measurements, all types of liquid
chromatography, PAGE, IEF, immunoassay, Western, filter binding assays, UV
spectroscopy. Automated electrophoresis based on high throughput microfluidic
technology
MOLECULAR BIOLOGY: P1, T7, f1, M13, T7 phage display, substrate DNA
construction, site specific modification and purification for biochemical
studies, vector construction, bacmid, plasmid and phage DNA preparation, PCR,
Southern hybridization
CELL BIOLOGY: mammalian and insect cell culture, monoclonal antibody, mouse
work
AWARDS
AACR-AFLAC Scholar in Cancer Research Awards 1999, 2000
LANGUAGE and SCIENTIFIC TRANSLATION
Native of Russia, fluent in Russian and English
Translated and edited manuscripts for publication in English
PUBLICATIONS
1. Iyer RR, Pohlhaus TJ, Chen S, Hura GL, Dzantiev L, Beese LS, Modrich P. The
MutS-Proliferating Cell Nuclear Antigen Interaction in Human DNA Mismatch
Repair. J. Biol. Chem., 283, 13310 (2008).
2. Kadyrov, F.A., Dzantiev, L., Constantin, N.,and Modrich, P. Endonuclease
Function of MutL in Human Mismatch Repair. Cell, 126, 297 (2006).
3. Constantin, N., *Dzantiev, L., Kadyrov, F.A., and Modrich, P. Human Mismatch
Repair: Reconstitution of a nick-directed bidirectional reaction. J. Biol.Chem,
280, 39752 (2005).
4. Dutta, S., Ying, L., Johnson, D., Dzantiev, L., Richardson, C.C., Romano,
L.J., and Ellenberger, T. Crystal Structures of N-2-Acetylaminofluorene and
N-2-Aminofluorene in Complex With T7 DNA Polymerase Reveal Mechanisms of
Replication Blockage and Mutagenesis. Proc. Natl. Acad. Sci. USA. 101, 16186
(2004).
5. *Dzantiev, L., Constantin, N., Genschel, J., Iyer, I.R., Burgers, P.M., and
Modrich, P. A Defined Human System That Supports Bidirectional Mismatch-Provoked
Excision. Molecular Cell, 15, 31 (2004).
6. Dzantiev, L., Alekseyev, Yu.O., Morales, J.C., Kool, E.T., and Romano, L.J.
Significance of Nucleobase Shape Complementarity and Hydrogen Bonding in the
Formation and Stability of the Closed Polymerase – DNA Complex. Biochemistry,
40, 3215 (2001).
7. Alekseyev, Yu.O., Dzantiev, L., and Romano, L.J. Effects of Benzo[a]pyrene
DNA Adducts on Escherichia coli DNA Polymerase I (Klenow fragment)
Primer-Template Interactions: Evidence for Inhibition of the Catalytically Active
Ternary Complex Formation. Biochemistry, 40, 2282 (2001).
8. Dzantiev, L. and Romano, L. J. Differential Effects of
N-Acetyl-2-aminofluorene and N-2-Aminofluorene Adducts on the Conformational
Change in the Structure of DNA Polymerase I (Klenow Fragment). Biochemistry, 39,
5139 (2000).
9. Dzantiev, L. and Romano, L.J. A Conformational Change in E. coli DNA
Polymerase I (Klenow Fragment) is Induced in the Presence of a dNTP Complementary
to the Template Base in the Active Site. Biochemistry, 39, 356 (2000).
10. Dzantiev, L. and Romano, L.J. Interaction of Escherichia coli DNA
Polymerase I (Klenow Fragment) with Primer-Templates Containing
N-Acetyl-2-aminofluorene or N-2-Aminofluorene Adducts in the Active Site. J.
Biol.Chem., 274, 3279 (1999).
11. Zherdev, A.V., Dzantiev, B.B., Popov, V.O., Dzantiev, L.B., Kirby, A.J.,
Sviridov, V.V., and Yakovleva, I.V. Production and Characterization of
Antibodies toward a Sulfur-containing Hapten, and Analogue of the Lactamization
Reaction Transition State. Applied Biochemistry and Microbiology, 33, 557
(1997).
*-shared first authorship
Presented posters at 14 scientific meetings, gave talks at 2 international
(AACR) conferences
REFERENCES
Available upon request
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