Laboratory of Molecular Medicine

Pavel P.Laktionov

Ph.D.
Phone: +7(383) 363-51-43, Email

• Cell free and cell-surface-bound extracellular/circulating nucleic acids (cirNA) - origin, circulation, elimination from biological fluids and investigation by whole genome study methods.
• Development of cirNA-based non-invasive cancer diagnostics .
• Investigation of the natural transport of nucleic acids into mammalian cells and proteins mediating transport of nucleic acids into cells/intracellular compartments.
• Influence of extra cellular nucleic acids onto innate immunity. Development of anticancer DNA vaccines.
• Development of novel materials and technologies for 3D cell culture and tissue replacement therapy.

• Methods for quantitative isolation and quantification of nucleic acids from biological samples were developed. [Patent RF N.2272072, 2004; N.2311640, 2006; Anal. Biochem. 2003, 322(1), 48].
• Cell-free DNA circulating in blood of healthy donors and breast cancer patients were investigated. It was shown that more than 95% cirDNA in blood of healthy donors are absorbed at the surface of blood cells whereas main part cirDNA in blood of breast cancer patients circulate as free DNA in blood plasma. [Ann. N.Y. Acad. Sci. 2004. 1022, 221].
• It was shown that aberrantly methylated tumor-specific DNA circulating in blood of cancer patients are more frequently bound with cell surface of blood cells than in plasma. Patients with breast tumors were shown to possess high level of methylated genes RASSF1A and RAR2. Thus the level of methylation of these genes in total cirDNA presents available information for non-invasive breast cancer diagnostics. [Clin. Chem. 2005, 51(7), 1317; Br J Cancer. 2006, 94(10), 1492].
• It was shown that copy number of 18S rRNA and mRNA of RASSF8 and Ki-67 genes in blood breast cancer increased in comparison with clinically healthy person and patients with non-malignant tumors. Estimation of these RNAs concentration in the pool of cirRNA allows to differentiate malignant from non-malignant breast tumor with sensitivity (82%) and specificity (92%). [Biomedical Chemistry (Rus.). 2008. 54(1), 94].
• It was shown that RT-PCR detection of aberrantly methylated genes p15 and hMLH1 in the pool of total circulating DNA of gastric cancer patients is at least 2 times more sensitive than analysis of common protein markers. [Ann. N.Y. Acad. Sci. 2008. 1137, 226, Biomedical Chemistry (Rus.). 2009. 55, 15].
• Using affinity modification followed by affinity chromatography/mass-spectroscopy the proteins responsible for binding of nucleic acids with surface of keratinocytes were identified. [Biochemistry (Rus.). 2003. 68(11), 1540; Ann. N.Y. Acad. Sci. 2004. 1022, 239].
• The method for efficient ligation of oligonucleotide adaptors to single stranded nucleic acids in fento/pico-molar concentrations was developed. [Patent RF N.2322508, 2006].
• Novel approaches for identification of short nucleic acids fragments responsible for binding endogeneous DNA with cell surface were developed and the fragments were isolated and sequensed. [Patent RF N.2393230, 2010; Ann. N.Y. Acad. Sci. 2008. 1137, 47].
• Extracelluar cirDNA were shown to inhibit immunostimulating action of dsRNA. Specific sequences demonstrating such activity were found. [Circulating Nucleic Acids in Plasma and Serum. Ed P.B. Gahan, Springer. 2011, Part 5, 207].
• The protocol for preparative isolation of apyrogenic plasmid DNA for gene immunization was developed. [Patent RF N.2408729, 2009].
• The method for isolation of rare cells circulating in blood based on microchannel silicon matrices was developed. [Patent RF N.2423698, 2009].

1. Morozkin E.S., Karamysheva T.V., Laktionov P.P., Vlassov V.V., Rubtsov N.B. DNA probes for FISH analysis of C-negative regions in human chromosomes. Methods Mol Biol. 2013. 1039, 233-242.
2. Cherepanova A.V., Bushuev A.V., Kharkova M.V., Vlassov V.V., Laktionov P.P. DNA inhibits dsRNA-induced secretion of pro-inflammatory cytokines by gingival fibroblasts. Immunobiology. 2013. 218(2), 272-280.
3. Ponomaryova A.A., Rykova E.Y., Cherdyntseva N.V., Dobrodeev А.Y., Zav’yalov A.А., Bryzgalov L.O., Tuzikov S.A., Vlassov V.V., Laktionov P.P. Potentialities of aberrantly methylated circulating DNA for diagnostics and post-treatment follow-up of lung cancer patients. Lung Cancer. 2013. 81(3), 397-433.
4. Morozkin E.S., Zaporozhchenko I.A., Kharkova M.V., Cherepanova A.V., Laktionov P.P., Vlassov V.V., Sukhov B.G., Prozorova G.F., Ttrofimov B.A., Khvostov M.V., Tolstikova T.G. Cytotoxic and Immunomodulating Properties of Silver and Platinum Nanocomposites. Chemistry for Sustainable Development. 2013. 21(2), 155-163.
5. Kharkova M.V., Cherepanova A.V., Morozkin E.S., Zaporozhchenko I.A., Laktionov P.P., Strunov A.A., Kiseleva E.V., Tolstikova T.G., Shikina N.V., Ismagilov Z.R., Vlassov V.V. Cytotoxic and Immunomodulating Properties of Gold Nanoparticles. Chemistry for Sustainable Development. 2013. 21(2), 179-188.
6. Cortese.R., Kwan A., Lalonde E., Bryzgunova O.E., Bondar A.A., Wu Y., Gordevicius J., Oh G., Kaminsky Z., Tverkuviene J., Laurinavicius A., Jankevicius F., Sendorek DNS., Haider S., Wang S.C., Jarmalaite S., Laktionov P.P., Boutros P.C., Petronis A. Epigenetic markers of prostate cancer in plasma circulating DNA. Human molecular genetics. 2012. 21(16), 3619-3631.
7. Cherepanova A.V., Bushuev A.V., Duzhak T.G., Vlassov V.V., Laktionov P.P. Ku protein as the main cellular target of cell-surface-bound circulating DNA. Expert Opin. Biol. Ther. 2012. 12(S1), 35-41.
8. Morozkin E.S., Loseva E.M., Morozov I.V., Kurilschikov A.M., Bondar A.A., Rykova E.Y., Vlassov V.V., Laktionov P.P. A comparative study of cell-free apoptotic and genomic DNA using FISH and massive parallel sequencing. Expert Opin. Biol. Ther. 2012. 2(S1), 11-17.
9. Rykova E.Y., Morozkin E.S., Ponomoreva А.А., Loseva E.M., Zaporozhchenko I.A., Cherdyntseva N.V., Vlassov V.V., Laktionov P.P. Cell-free and cell-bound circulating nucleic acid complexes: mechanisms of generation, concentration and content. Expert Opin. Biol. Ther. 2012. 12(S1), 141-153.
10. Klimenko Е.S., Zaporozhchenko I.A., Mileyko V.A., Morozkin E.S., Koulintchenko М.V., Laktionov P.P., Konstantinov Yu.М. Human cultured cells are capable to incorporate isolated plant mitochondria loaded with exogenous DNA. Biopolymers & Cell. 2012. 28(4), 310-313.
11. Romanov S.I., Pyshnyi D.V., Laktionov P.P. Sensors and filters based on nano- and microchannel membranes for biomedical technologies. Journal of Physics: Conference Series. 2012. 345(1), 1-6.
12. Khatuntseva E.A., Men'shov V.M., Shashkov A.S., Tsvetkov Y.E., Stepanenko R.N., Vlasenko R.Y., Shults E.E., Tolstikov G.A., Tolstikova T.G., Baev D.S., Kaledin V., Popova N.A., Nikolin V.P., Laktionov P.P., Cherepanova A.V., Kulakovskaya T.V., Kulakovskaya E.V., Nifantiev N.E. Triterpenoid saponins from the roots of Acanthophyllum gypsophiloides Regel. Beilstein J. Org Chem. 2012. 8, 763-775.
13. Anna V. Cherepanova, Alexander V. Bushuev, Valentin V. Vlassov, Pavel P. Laktionov. Cell-surface-bound DNA inhibits poly(I:C)-activated IL-6 and IL-8 production in human primary endothelial cells and fibroblasts. Circulating Nucleic Acids in Plasma and Serum. Ed P.B. Gahan. Springer. 2011. Part 5, 207-211.
14. Bryzgunova O., Bondar A., Morozkin E., Mileyko V., Vlassov V., Laktionov P. A reliable method to concentrate circulating DNA. Anal. Biochem. 2011. 408(2), 354-356.
15. Morozkin E.S., Loseva E.M., Karamysheva T.V., Babenko V.N., Laktionov P.P., Vlassov V.V., Rubtsov N.B. A Method for Generating Selective DNA Probes for the Analysis of C-Negative Regions in Human Chromosomes. Cytogenet. Genome. Res. 2011. 135(1), 1-11.
16. Ponomaryova A.A., Rykova E.Y., Cherdyntseva N.V., Skvortsova T.E., Dobrodeev А.Y., Zav’yalov A.А.,Tuzikov S.A., Vlassov V. V., Laktionov P. P. RARβ2 gene methylation level in the circulating DNA from lung cancer patient blood. Eur J Cancer Prev. 2011, 20(6), 453-455.
17. Ponomaryova A.A., Rykova E.Y., Cherdyntseva N.V., Skvortsova T.E., Cherepanova A.V., Morozkin E.S., Mileiko V.A., Litvjakov N.V., Dobrodeev А.Y., Zav’yalov A.А., Tuzikov S.A., Chikova E.D., Vlassov V.V., Laktionov P.P. Concentration and distribution of single-copy β-actin gene and LINE-1 repetitive elements in blood of lung cancer patients. Circulating Nucleic Acids in Plasma and Serum. Ed P.B. Gahan, Springer. 2011, Part 2. 41-45.
18. Morozkin E.S., Loseva E.M., Mileyko V.A., Zadesenets K.S., Rubtsov N.B., Vlassov V.V., Laktionov P.P. Comparative study of extracellular DNA by FISH. Circulating Nucleic Acids in Plasma and Serum. Ed P.B. Gahan. Springer. 2011. Part 3, 143-146.
19. Skvortsova T.E. Bryzgunova O.E., Lebedeva A.О., Mak V.V., Vlassov V.V., Laktionov P.P. Methylated Cell-free DNA in Vitro and in Vivo. Circulating Nucleic Acids in Plasma and Serum. Ed P.B. Gahan. Springer. 2011. Part 5, 185-194.

• Laktionov P.P., Vajner O.B., Zaporozhchenko I.A., Pyshnaya I.A., Pyshnyi D.V., Dmitrienko E.V., Romanov S.I., Vlasov V.V. Method of selective recovery of viable cell population from biological fluids. Patent RF N.2423698, 2011.
• Laktionov P.P., Cherepanova A.V., Skvortsova T.E., Chernonosova V.S., Morozkin E.S., Prokhorenko V.M., Nechaeva E.A., Vlassov V.V. Method for production of plasmid DNA from bacterial cells. Patent RF N.2408729, 2011.

RFBR (Grants of the Russian Foundation for Basic Research)

• N.12-04-31365 “Transport of eugenic deoxy- and ribonucleic acicd in blood: investigation of proteome of nucleoprotein complexes and microvesicules circulating in blood” (2012-2013)
• N.13-04-01460 “Intramoleucular diversity of potential epigenetic DMA-markers of prostate cancer: investigation of functional importance and diagnostic potentialities” (2013-2015)

Interdisciplinary Integration Projects of the Presidium of SB RAS (2012-2014)

• N.75 “Development of novel approaches for tissue engeneering of blood vessels”
• N.65 “Metaepigenom circulating in blood of cancer patients as general characteristics of tumor progression: novel approach for revealing of DNA and RNA oncomarkers for non-invasive diagnostics and teranostics of tumors”
• N.84 “Natural microvesicules and complexes, nhfysporting nucleic acids: properties, biological functions and perspectives of diagnostics and tearupeutic application”

Programs of the Presidium of RAS N.5 “Basic Sciences for medicine”

• N.18 “Detailed study of aberrantly methylated circulating DNA of RNF219, ZC3H4 and KIAA1539 genes – novel potential markers of prostate cancer“ (2013-2015)

N.6 “Molecular and cell biology”

• N.1 “Biochemistry of extracellular nucleic acids and design of new types of the gene directed biologically active compounds” (2013-2017)

Russian President’ scholarship for young scientists and graduate students (2013-2015)

• SP-1528.2013.4 “Dig for potential markers of prostate cancer in exosomes and exosome liker structures circulating in blood and urine” (Bryzgunova O.E.)
• SP-5711.2013.4 “Immunomodulating effects of extracellular nucleic acids” (Cherepanova A.V.)
• SP-4710.2013.4 “Intramoleucular diversity of potential epigenetic DMA-markers of prostate cancer: investigation of functional importance and diagnostic potentialities” (Bondar A.A.)

• Spectrophotometer (Genesys 10uv, Thermo Electronics, United States);
• fluorimeter (VersaFluorTM, BioRed);
• microplate reader (SDB NP Puschino, Russia);
• bioreactor for bacteria cultivation;
• Pyrosequencing PSQ 96 DNA Sequencer (PyroMark ID, Pyrosequencing AB, Sweden);
• inverted microscopes equipped with CCD cameras (Axiovert 40C, AxioCam ICc 3, Zeiss, Gemany);
• inverted fluorescent microscope (Axiovert 200 M (motorized) with apotome, СO2 and thermo modulus, micromanipulators (Narishigi), Zeiss, Germany);
• Electrospinning set up (NF 103, MECC, Japan); Viscosimeter DV-II+ Pro (Brookfield, USA).