Center for Radiological Research
630 W. 168th St.
New York, NY 10032
Tel: (212) 305-3911
Fax: (212) 305-3229
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
M.Sc. with honor, Moscow State University, Moscow, Russia, 1991
Ph.D., Russian Academy of Sciences, Moscow, 1996
Academic and Professional Appointments
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
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.
Journal articles (15 printed works):
S, Mezentsev A, Kalachikov S, Raith K,
Roop DR and Panteleyev AA. Targeted ablation of Arnt in
mouse epidermis results in profound defects in desquamation
and epidermal barrier function. J Cell Sci 119:4901-12,
A, Mastyugin V, Seta F, Ashkar S, Kemp R, Reddy
DS, Falck JR, Dunn MW and Laniado-Schwartzman M. Transfection
of cytochrome P4504B1 into the cornea increases angiogenic
activity of the limbal vessels. J Pharmacol Exp Ther
315:42-50, 2005. [abstract]
A, Merks RM, O'Riordan E, Chen J, Mendelev N,
Goligorsky MS and Brodsky SV. Endothelial microparticles
affect angiogenesis in vitro: role of oxidative stress.
Am J Physiol Heart Circ Physiol 289:H1106-14,
Volti G, Sacerdoti D, Sangras B, Vanella A, Mezentsev
A, Scapagnini G, Falck JR and Abraham NG. Carbon
monoxide signaling in promoting angiogenesis in human
microvessel endothelial cells. Antioxid Redox Signal
7:704-10, 2005. [abstract]
V, Mezentsev A, Zhang WX, Ashkar S, Dunn
MW and Laniado-Schwartzman M. Promoter activity and regulation
of the corneal CYP4B1 gene by hypoxia. J Cell Biochem
91:1218-38, 2004. [abstract]
Published Abstracts & Letters (26 posters and oral presentations):
A and Amundson SA. Response to low and high doses
of proton irradiation in 3-dimensional tissue model Epi-200.
The 54th Annual Meeting of The Society for Radiological
Research, Boston, 2008.
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, Washington DC, 2007.
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.
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.
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,
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. ARVO,
Program Summary Book, 2005.
for CV and full list of publications