MEZENTSEV, Alexandre V, PhD

3 Gubkina Street, room 302 Phone 7-499-132-0874

Moscow 119991, Russia [email protected]

PROFESSIONAL PROFILE:

Leading Scientist in Functional Genomics, with 14 years of experience in Life Sciences and broad experience in Biochemistry and Molecular Biology, research and academic achievements in protein chemistry, molecular and cellular biology, pharmacology, radiation oncology, and dermatology. Extremely hard working and well-organized individual with a preference to work in a multidisciplinary team, has advanced communication, leadership and teamwork skills.

Accurate and detail-oriented scientist capable to write grants and protocols will prepare manuscripts and reports and present the results.

Experienced researcher who has the capability to design his own troubleshooting or follow an existing one and work under minimal supervision or independently supervising junior colleagues.

Areas of Expertise

1. Analysis of protein-protein interactions

2. Characterization of kinase-regulated pathways and transcriptional regulation;

3. Viral transduction and cell transfection

4. Carcinogenic effects of ionizing radiation and apoptosis in the irradiated cells

5. Immunocytochemistry and histochemistry; Quantitative immunoassays (Western, ELISA etc)

6. Computer applications for Image analysis (e.g. ImageJ, Image Pro Express), presentations (e.g. Origin, Prizm, Fig);

7. Microarray-qPCR and Bioinformatics

8. DNA/RNA work (e.g. blotting, labeling, hybridization, scanning) and analysis

9. Protein chemistry and Purification (including HPLC and 2D)

10. Animal work: breeding and maintenance of mice colonies, genotyping.

Core Accomplishments

1. Identified molecular signature of psoriasis by applying global gene expression approach to analysis of skin samples from healthy volunteers and patients;

2. Identified 38 novel bystander genes in skin tissue samples exposed to ionizing radiation;

3. Characterized new phenotype of transgenic mice with conditional ablation of Arnt expression in the epidermis;

4. Characterized new class of signaling molecules (12-HETE and 12R-HETrE) with an active role in the inflammatory process, cloned rabbit CYP4B1 and promoter;

5. Contributed to the discovery of the molecular basis of the lysosomal storage disease, beta-galactosialidosis in a study of protein-protein interactions in high molecular weight glycoprotein complexes;

Professional Chronology

1. 06/11-present: Leading Scientist, IOGEN (Russia), Department of Functional Genomics (Moscow, Russia).

2. 12/06-10/10: Associate Research Scientist, COLUMBIA UNIVERSITY, Department of Radiation Oncology, Center for Radiological Research (New York, NY 10032).

3. 12/05-12/06: Postdoctoral Fellow, COLUMBIA UNIVERSITY, Department of Dermatology, (New York, NY 10032).

4. 01/00-12/05: Postdoctoral Research Associate, NEW YORK MEDICAL COLLEGE, Department of Pharmacology (Valhalla, NY 10595).

5. 01/97-09/98: Postdoctoral Fellow, ST. JUSTINE CHILDREN'S HOSPITAL, Service of medical genetics (Montreal, QC Canada).

Education

RUSSIAN ACADEMY OF SCIENCES, INSTITUTE OF BIOCHEMISTRY (Moscow, Russia)

PhD, Biochemistry - 1996

MOSCOW STATE UNIVERSITY, Department of Biology (Moscow, Russia)

Master's, Biochemistry (GPA 3.68) - 1991

Summa cum laude

Thesis/Dissertation

To define the molecular mechanism of NAD⁺-dependent formate dehydrogenase (FDH), several point mutations were introduced to the enzyme active center by the method of site-directed mutagenesis. The recombinant proteins were expressed in E. coli and their pH dependences with different substrates and inhibitors and spectral properties were analyzed. The study identified that the enzymatic reaction involved the hydrate transfer, which also was its rate-limiting stage. V_max of the enzymatic reaction remained stable between pH 6.0 and 11.2 while dropped below 6 suggesting a role two carboxyl groups in achievement of the transition state. Affinity to NAD⁺ dropped above pH 10.5 suggesting a role of an arginine residue in binding of the coenzyme. Analysis of the recombinant proteins confirmed role of Arg284 in binding of coenzyme and two closely located aspartate residues (Asp221 and Asp308) in binding of formate anion. Analysis of the enzyme inhibitors, CNS^-, CNO^-, N₃^-, and ADPR suggested that FDH purified from methylotrophic bacteria Pseudomonas sp. 101 bound the substrates independently while FDH purified from methylotrophic yeast Hansenula polymorpha bound NAD⁺ prior formate anion and released CO₂ prior NADH. Competition of formate anion and pyridoxal suggested an existence of a substrate channel that points formate anion to the enzyme active center and presence in this channel of a lysine residue. The following X-ray analysis of FDH crystals performed at high resolution (2Å) confirmed an existence of the cannel and role of Lys286 in binding of pyridoxal. Thus, FDH catalyzed reaction occurred due to a transfer of hydride anion from formate anion to NAD⁺. Arg284 contributed to binding of the coenzyme, Asp221 and Asp308 - to binding of formate anion. The enzyme structure had a substrate channel that could be blocked by pyridoxal due to a covalent modification of Lys286.

Awards

NASA Space Radiation Program ("NSRSS") THE BROOKHAVEN NATIONAL LABORATORY,

Long Island, New York Grant to attend with full Scholarship - 2007

Travel award, 7th Annual Winter Eicosanoid Conference, Baltimore for meritorious scientific

Abstract - 2005

Award for the best oral presentation at the Annual Meeting in AN Bakh Institute of Biochemistry

(Moscow, Russia) - 1996

M. Sc. diploma in biology with honor, Moscow State University, Department of Biology (Moscow,

Russia) - 1991

Affiliations

RRS, Radiation Research Society - 2008-2010

ARVO, The Association for Research in Vision and Ophthalmology - 2001-2006

SID, Society for Investigative Dermatology - 2006

WEB SITES:

http://mesentsev.fortunecity.com (English)

http://mesentsev.narod.ru/ (Russian)

C. PUBLICATIONS:

Refereed Journal Articles:

1.	Wondimu A, Weir L, Robertson D, Mezentsev A, Kalachikov S, Panteleyev AA. Loss of Arnt (Hif1β) in mouse epidermis triggers dermal angiogenesis, blood vessel dilation and clotting defects. Lab Invest. 2011 Sep 26. doi: 10.1038/labinvest.2011.134.
2.	Mezentsev A, Amundson SA. Global gene expression responses to low- or high-dose radiation in a human three-dimensional tissue model. Radiat Res. 2011 175(6): 677-88.
3.	Seta F, Patil K, Bellner L, Mezentsev A, Kemp R, Dunn MW, Schwartzman ML. Inhibition of VEGF expression and corneal neovascularization by siRNA targeting cytochrome P450 4B1. (2007) Prostaglandins Other Lipid Mediat. 84(3-4), 116-27.
4.	Geng S., Mezentsev A., Kalachikov S., Raith K., Roop D. and Panteleyev A. Targeted ablation of Arnt in mouse epidermis results in profound defects in desquamation and epidermal barrier function (2006) J Cell Sci. 119(23), P4901-12.
5.	Mezentsev A, Mastyugin V, Ashkar S, Seta F, Reddy S, Falck JR and Laniado-Schwartzman M. Transfection CYP4B1 into the cornea increases angiogenic activity of the limbal vessels (2005) J Pharmacol Exp Ther. 315(1), P42-50.
6.	Mezentzev A, Merks RMH., O’Riordan E, Chen J, Mendelev N, Goligorsky MS and Brodsky SV. Endothelial microparticles affect angiogenesis in vitro: the role of oxidative stress. (2005) Am J Physiol Heart Circ Physiol. 289(3), H1106-14
7.	Li Volti G, Sacerdoti D., Sangras B, Vanella A, Mezentsev A, Scapagnini G, Falck JR and Abraham N. Carbon monoxide signaling in promoting angiogenesis in human microvessel endothelial cells (2005) Antioxidants and Redox Signal. Vol. 7, N5-6, P. 704-710.
8.	Mastyugin V, Mesentsev A, Wen-Xiang Zhang, Ashkar S, Dunn MW and Laniado- Schwartzman M. Promoter activity and regulation of the corneal CYP4B1 gene by hypoxia. (2004) J. Cell. Biochem. Vol. 91, N6, P.1218-38
9.	Ashkar S, Mesentsev A, Wen-Xiang Zhang, Mastyugin V, Dunn MW and Laniado- Schwartzman M Retinoic acid induces corneal epithelial CYP4B1 gene expression and stimulates the synthesis of inflammatory 12-hydroeicosanoids (2004) J. Cell. Pharm. Therapeutics, Vol. 20, N1, P.65-74
10.	Jiang M, Mesentsev A, Byun K, Falck JR, Miano JM, Abraham NG and Laniado- Schwartzman M. Smooth muscle-specific expression of CYP4A1 induces endothelial sprouting in renal arterial microvessels (2004) Circ. Res. Vol. 94, N2, P.65-74
11.	Laniado- Schwartzman M, Bonazzi A, Mieyal P, Mesentsev A, Abraham NG and Dunn MW. COX-2 lack of function in hypoxia-induced ocular surface inflammation (2003) Thrombosis Res. (2003) Vol. 110 N 5-6, P. 293-298
12.	Mezentsev AV, Seta F, Dunn, MW, Ono N, Falck, JR and Laniado-Schwartzman M. The angiogenic activity of 12(R)-hydroxyeicosatrienoic acid is mediated by vascular endothelial growth factor (VEGF). (2002) J. Biol. Chem. Vol. 277, N21, P.18670-18676
13.	Malaguarnera L, Pilastro MR, Quan S, Ghattas MH, Yang L, Mezentsev AV, Kushida T, Abraham NG and Kappas A. Significance of heme oxygenase in prolactin- mediated cell proliferation and angiogenesis in human endothelial cells. Int. J. Mol. Med. (2002) Vol. 10, N4, P.433-40.
14.	Galkin AG, Kutsenko AS, Bajulina NP, Esipova NG, Lamzin VS, Mesentsev AV, Shelukho DV, Tikhonova TV, Tishkov VI, Ustinnikova TB and Popov VO. Site-directed mutagenesis of the essential arginine of the formate dehydrogenase active centre. (2002) Biochim. Biophys. Acta. Vol. 1594, N1 P.136-49
15.	Vinogradova MV, Mezentsev AV, Lukong KE, El-Alfy M, Morales CR, Michaud L and Pshezhetsky AV. Molecular mechanism of the sialidase deficiency in galactosialidosis involves its rapid degradation. (1998) Biochem. J., Vol. 330, N2, P.641-650
16.	Mesentsev AV, Lamzin VS, Tishkov VI, Ustinnikova TB and Popov VO. Effect of pH on kinetic parameters of NAD-dependent formate dehydrogenase. (1997) Biochem. J. Vol. 321, P. 475-480
17.	Tishkov VI, Matorin AD, Rojkova AM, Fedorchuk VV, Savitsky PA, Dementieva LA, Lamzin VS,Mesentzev AV and Popov VO. Site-directed mutagenesis of the formate dehydrogenase active centre: role of the His332-Gln313 pair in enzyme catalysis. (1996) FEBS Lett. Vol. 390, P. 104-108
18.	Mezentsev AV, Ustinnikova TB, Tikhonova TV and Popov VO. Isolation and kinetic mechanism of action of NAD- dependent formate dehydrogenase from methylotrophic yeast Hansenula polymorpha. (1996) Applied Biochemistry and Microbiology (Moscow) Vol. 32, N 6, P. 850-854
19.	Matveeva LN, Bekkali M and Mezentsev AV, Functional role of cysteine residues of muscle succinyl- CoA- synthetase. (1992) Proc. Natl. Acad. Sci. USSR, Vol. 324, P.4885-4889

Oral Presentations:

1.	Mezentsev AV and Bruskin SA. Biomarkers and molecular mechanism of psoriasis. The 10th Russian-American collaboration workshop on biomarkers of the diseases. (2012) Moscow
2.	Mezentsev A, Kalachikov SM. And Panteleyev AA. Regulation of Epidermal Late- Differentiation Genes via Arnt-dependent Pathway in Primary Mouse Keratinocytes Requires Chromatin Remodeling. Society for Investigative Dermatology Annual Meeting (2006) J. Invest. Derm. 126, S4, P.69
3.	Mezentsev A, Seta F, Kemp R, Dunn MW and Laniado-Schwartzman M. The Corneal epithelial CYP4B1 produces angiogenic eicosanoids and induces inflammation of the ocular surface (2005) ARVO, Program Summary Book

Published Abstracts & Letters:

1.	Amundson SA, Brenner DJ and Mezentsev A. Low dose and bystander responses in a 3-D human skin model. 2011 Low dose radiation research investigators workshop (2011) Bethesda MD.
2.	Amundson SA, Brenner DJ and Mezentsev A. Effects of low fluence HZE ions on 3-dimensional skin tissue. 2010 Low dose radiation research investigators workshop (2010) Bethesda MD.
3.	Sack R, Cooper B, Bellner L, Mezentsev A, Laniado-Schwartzan M, Beaton A, Sathe S, Istroavich P. Diurnal-distribution and selective down regulation of cytokines in tears (2011) ARVO, Program Summary Book
4.	Mezentsev A. and Amundson S.A. Bystander effects of alpha particles in 3-dimensional tissue model. The 55^th Annual Meeting of Society for Radiological Research (2009), Savannah, GA.
5.	Amundson SA, Brenner DJ and Mezentsev A. Structural damage and novel low dose signaling pathway in a human 3-D tissue model. The 8th Low dose radiation workshop (2009) Bethesda MD.
6.	Robertson D, Weir L, Wondimu A, Mezentsev A, Panteleyev A The 37^th Annual Meeting of European Society for Dermatological Research (2009), Budapest, Hungary.
7.	Mezentsev A. and Amundson S.A. Response to low and high doses of proton irradiation in 3-dimensional tissue model Epi-200. The 54^th Annual Meeting of Society for Radiological Research (2008), Boston, MA.
8.	Kalachikov S, Weir L, Robertson D, Mezentsev AV and Panteleyev AA. The role of Arnt gene in the control of desquamation and epidermal barrier formation in mouse skin, P23. British Society of Investigative Dermatology, Annual Meeting (2008), Oxford, UK
9.	Amundson SA, Brenner DJ and Mezentsev A. Mechanistic and quantitative studies of bystander responses in 3-D tissues for low-dose radiation risk estimation. The 7th Low dose radiation workshop (2007) Washington D.C.
10.	Panteleyev A, Wondimu A, Kalachikov S, Mezentsev A, Geng S. Loss of Arnt (Hif-1b) in mouse epidermis triggers paracrine epidermal-dermal signaling and alterations in dermal vasculature. The 37^th Annual Meeting of European Society for Dermatological Research (2007), Zürich, Switzerland.
11.	Geng S., Mezentsev A., Miho I, Kalachikov SM. and Panteleyev AA. The Role of Arnt gene in Perinatal Mouse Skin Neovascularization. Society for Investigative Dermatology Annual Meeting (2006) J. Invest. Derm. 126, S4, P.4
12.	Mezentsev A, Kalachikov SM. And Panteleyev AA. The Patterns of Periderm Shedding in Mice and the Role of Arnt in Regulation of This Process. Society for Investigative Dermatology Annual Meeting (2006) J. Invest. Derm. 126, S4, P.69
13.	Schwartzman ML, Seta F, Bellner L, Mezentsev A, Dunn MW. Inhibition of VEGF Expression and Corneal Neovascularization by siRNA Targeting the Cytochrome P450 (CYP) 4B1. (2006) ARVO, Program Summary Book
14.	Seta F, Mezentsev A, Dunn MW and Laniado-Schwartzman M. The corneal-derived 12(R)-hydroxyeicosatrienoic acid (12-HETrE) stimulates IL-8 production in microvessel endothelial cells (2005) ARVO, Program Summary Book
15.	Laniado-Schwartzman M, Mezentsev A, Seta F, Dunn MW, Abraham NG and Gronert K Heme Oxygenase-2 (HO-2) Knockout Mice Display Impaired Corneal Wound Healing and Marked Corneal Neovascularization (2005) ARVO, Program Summary Book
16.	Mezentsev A, Mastyugin V, Ashkar S, Seta F, Reddy S, Falck JR and Laniado-Schwartzman M. Transfection CYP4B1 into the cornea increases angiogenic activity of the limbal vessels (2005) The 7th Annual Winter Eicosanoid Conference, Program Summary Book.
17.	Seta F, Mezentsev A, Dunn MW, Gronert K, Abraham NG, and Laniado-Schwartzman M. Heme oxygenase-2 (HO-2) null mice impaired corneal wound healing and marked neovascularization (2005) The 7th Annual Winter Eicosanoid Conference, Program Summary Book.
18.	Mezentsev A, Seta F, Dunn MW and Laniado-Schwartzman M. Transfection of CYP4B1 into the cornea induces angiogenic activity in the limbal vessels. (2004) ARVO, Program Summary Book
19.	Seta F, Mezentsev A, Dunn MW and Laniado-Schwartzman M. Corneal-derived 12(R)-hydroxyeicosatrienoic acid (12-HETrE), stimulates limbal endothelial angiogenesis via Erk1/2 independent of Ras/Raf activation. (2004) ARVO, Program Summary Book
20.	Jiang M, Mezentsev A, Kemp R, Byun K, Falck JR, Miano J, Nasjletti A, Abraham NG and Laniado-Schwartzman M. Smooth muscle-specific expression of CYP4A1 induces endothelial sprouting in renal arterial microvessels (2004) AAPS National Biotechnology Conference The Westin Copley Place, Boston, MA
21.	Mezentsev AV, Zhang W-X, Mastyugin V, Dunn, MW and Laniado- Schwartzman, M. Promoter activity and regulation of the corneal CYP4B1 gene by hypoxia (2003) ARVO, Program Summary Book, P. 35
22.	Seta F, Mezentsev A, Ashkar S, Dunn MW and Laniado-Schwartzman M. Angiogenic properties of the corneal epithelial metabolite 12(R)- hydroxyeicosatrienoic acid (12(R)-HETrE) in human microvessel endothelial cells. (2003) ARVO, Program Summary Book, P.94.
23.	Ashkar SC, Zhang W-X, Mezentsev AV, Mastyugin V, Dunn MW and Laniado- Schwartzman M. Retinoic acid induces corneal epithelial CYP4B1 gene expression and stimulates the synthesis of inflammatory 12-hydroxyeicosanoids. (2003) ARVO, Program Summary Book, P. 35.
24.	Sack R, Sathe S, Laniado- Schwartzman M, Mesentsev A and Morris C. Closed eye tear fluid contains a potent high molecular weight angiogenic factor. (2003) ARVO, Program Summary Book, P. 57.
25.	Seta F, Mezentsev A, Dunn MW and Laniado-Schwartzman M. 12(R)-hydroxyeicosatrienoic acid, a corneal epithelial derived eicosanoid, stimulates angiogenesis via Erk1/2 activation of VEGF induction. (2002) ARVO, Program Summary Book.
26.	Laniado-Schwartzman M, Mezentsev A, Mastyugin V, Bonazzi A and Dunn MW. The angiogenic activity of 12(R)-hydroxyeicosatrienoic acid is mediated by vascular endothelial growth factor (VEGF). (2001) IOVS, Vol. 42, N 4, P. S90.
27.	Mastyugin V, Mosad S, Bonazzi A, Mezentsev A, Dunn MW and Laniado-Schwartzman M, Corneal epithelial VEGF and CYP4B1 expression in a rabbit model of closed eye contact lens wear. (2001) IOVS, Vol. 42, N 4, P. S480.
28.	Kutsenko AS, Mezentsev AV and Popov VO. NAD-dependent formate dehydrogenase of methylotrophic bacteria Pseudomonas sp. 101: 3D-symmetry of domains (1996) Proceeding of the conference “Autotrophic microorganisms” (Moscow), Summary Book.
29.	Mezentseva NV, Kuznetsov DA, Mezentsev AV, Kutsenko AS, and Popov VO. NAD-dependent formate dehydrogenase of methylotrophic bacteria Pseudomonas sp. 101: mapping of the active center with pyridoxal and its analogues (1996). Proceeding of the conference “Autotrophic microorganisms” (Moscow), Summary Book.
30.	Mezentsev AV, Ustinnikova TB, Tikhonova TV, Tishkov VI and Popov VO. NAD-dependent formate dehydrogenase of methylotrophic bacteria Pseudomonas sp. 101: Role of the essential arginine (Arg284) in the enzyme catalysis. (1996) Proceeding of the conference “Autotrophic microorganisms” (Moscow), Summary Book.
31.	Mezentsev AV, Ustinnikova TB, Tikhonova TV, Tishkov VI and Popov VO. NAD-dependent formate dehydrogenase of methylotrophic bacteria Pseudomonas sp. 101: Effect of pH on kinetic parameters and enzyme catalysis. (1996) Proceeding of the conference “Autotrophic microorganisms” (Moscow), Summary Book.
32.	Tishkov VI, Galkin AG, Mezentsev AV, Ustinnikova, TB, Popov VO and Shelukho DV. Biocatalysis-95. Molecular mechanism of NAD-dependent formate dehydrogenase: Site-directed mutagenesis of the enzyme active centre (1996) Proceedings of the International Conference. Suzdal, Russia, August 28-September 1, 1995.In: Appl. Biochem. Biotechnol. Vol. 61, N1-2, pp. 1-209.
33.	Mezentsev AV, Galkin AG, , Ustinnikova TB, Shelukho DV, Tishkov VI and Popov VO Catalytic mechanism and application of formate dehydrogenase: Site-directed mutagenesis of the essential arginine in the enzyme active centre. (1996) Proceedings of the International Conference. Suzdal, Russia, August 28-September 1, 1995.In: Appl. Biochem. Biotechnol. Vol. 61, N1-2, pp. 1-209.

MANUSCRIPTS IN PREPARATION:

1	Mezentsev AV and Amundson SA. Mechanistic and quantitative studies of bystander responses in 3-D tissues for low-dose radiation risk estimation.
2.	Mezentsev AV and Amundson SA. Analysis of biological response to individual HZE particles (⁵⁶Fe) in 3-dimensional tissue model Epi-200. (2009) Carcinogenesis.