Alexandre Mezentsev, Ph.D.

Contact Information

Alexandre Mezentsev, Ph.D.
Center for Radiological Research
VC 11-215
630 W. 168th St.
New York, NY 10032

Tel: (212) 305-3911
Fax: (212) 305-3229
email: am2710@columbia.edu

Research Interests

Role of epidermis in mediation of postirradiational response
Bystander effect in 3-dimensional tissue models
Specific signature of ionizing radiation in gene expression
Induction of cytokines and eicosanoids in irradiated
and bystander cells

Current Research

My research in Columbia University is dedicated to the bystander effects in the epidermis induced by ionizing radiation. Particularly, we want to characterize the effects of small doses of irradiation in 3-dimensional skin models. Assuming that each kind of irradiation has own specific signature in the gene expression, we would identify differentially expressed genes and assess their contribution to the development of postirradiational responses. In the future, some of those misregulated genes will be used as biomarkers in diagnostic and assessment of the absorbed dose. Others will serve as potential targets for the newly developed pharmaceutical drugs.

Previously, the scientific community paid significantly more attention to the effects caused by the man-generated radiation. To the time, most of the data were obtained after an acute (short-time) exposure to a relatively high dose of gamma- or x- rays. NASA's plans to send piloted missions to the Moon and Mars raised the question of a potential risk of long-term radiation exposure for the human body. Furthermore, the space irradiation is quite different from one that we deal on the Earth. The cosmic rays have different composition and properties and their effects on the human body remain uncharacterized. This increases an actuality of the research like ours.

On the other hand, the extensive studies of postirradiational effects require an experimental model that would respond adequately to the impact. Unfortunately, the traditional approach employed by cell biologists has all these limitations of culturing the cells in a monolayer. Indeed, many scientists consider the cells as equal and independent units, which is not truth in the tissue. Role of intracellular contacts was often ignored or restricted to the interactions through the medium. In our opinion, it is hard to expect that cell behavior in a T- flask will correspond to one in vivo. Moreover, the prolonged cell culturing compromises the genome stability and promotes an accumulation of chromosome aberrations. My previous work in Biomedical Sciences, which involved multiple experiments with different kind of 3-dimensional tissue models and explants led me to the conclusion that 3-dimensional tissues remain the most adequate model to study processes that occur in the body.

In perspective, our studies will include functional genomic analysis of various aspects of the postirradiational effects, and a comparison of functional genomic responses to different kinds of ionizing radiation. In addition to the list of the specific genes those expression was affected by irradiation we would also identify the most fragile areas in the genome, which more frequently undergo the mutations. We expect that our studies will help us to answer the question whether the existing risk of the cosmic rays prevents us from sending the people to the space with a long- term mission and suggest a strategy to minimize the consequences of space radiation.

Academic Training
Undergraduate:	M.Sc. with honor, Moscow State University, Moscow, Russia, 1991
Graduate:	Ph.D., Russian Academy of Sciences, Moscow, 1996

Current Academic and Professional Appointments

Research Associate Scientist, Center for Radiological Research, College of Physicians & Surgeons of Columbia University

Publications

Some papers are available online in PDF format (requires Adobe Acrobat Reader, available for free download here: .
(http://www.adobe.com/products/acrobat/readstep2.html)

Refered Journal articles:

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.

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), 4, 901-12.

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.

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.

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.

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

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

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

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.

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.

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.

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

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.

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.

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

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

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

Published Abstracts & Letters:

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.

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.

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.

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

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.

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

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.

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.

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.

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

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

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

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

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.