Ph.D., Enhelhardt Institute of Molecular Biology
Office Phone: (216) 523-7199
Lab Phone: (216) 523-7554
COSHP Faculty Profile
Dr. Kondratov obtained his M.S. in Physics and Mathematics from Moscow Institute of Physics and Technology, his Ph.D. in Molecular and Cellular Biology from Enhelhardt Institute of Molecular Biology, and has post-graduate training in University of Illinois at Chicago and Cleveland Clinic Foundation. He has been a faculty member of Cleveland State University since 2006.
Our laboratory studies molecular mechanisms of aging and circadian rhythms. Recently we have found an unexpected functional connection between these two phenomena.
"The circadian system" or internal molecular clock is a genetically determined time keeping mechanism, which was developed by many organisms, from single cellular bacteria and fungi up to mammals including human, in order to adapt to 24-hour light/dark cycle. The circadian system controls daily oscillations of many behavioral and physiological processes such as locomotor activity, body temperature, food intake and sleep/wake. We have reported that knockout of the key circadian protein BMAL1 results in syndrome of early aging in mice - the significantly reduced life span (9 months for knockout vs. 28 months for wild type animals) and the development of multiple age-related pathologies (such as sarcopenia, osteoporosis, reduction of subcutaneous adipose tissue, decreased hair growth, cataracts, cornea inflammation, etc.).
Being a transcriptional factor, BMAL1 may orchestrate or influence many metabolic pathways in the organism. Therefore, different mechanisms may be responsible for aging and for the development of particular pathologies in BMAL1 deficient animals. Currently we are studying the role of BMAL1 in the control of ROS/RNS (reactive oxygen and nitrogen species) homeostasis and in the regulation of insulin-like growth factor/insulin-like growth factor receptor (IGF/IGFR) pathway. Both ROS and IGF/IGFR play important roles in diverse physiological processes and are strictly redulated through multiple feedback loops. Uncontrolled accumulation of ROS or impaired IGF/IGFR signaling result in serious injury of cells and tissues and are the major determinants of aging and age-related pathologies.
We use in vitro to in vivo systems, and different techniques and approaches in order to uncover the molecular mechanisms of the circadian control of aging. We are trying to understand the nature of such a principal factor in the aging process as the organism-environment interaction, and to identify molecular targets for anti-aging therapy.
1. Kondratov R.V., Chernov M.V., Kondratova A.A., Gorbacheva V., Gudkov A.V., and Antoch M.P. BMAL1-dependent circadian oscillation of nuclear CLOCK: posttranslational events induced by dimerization of transcriptional activators of the mammalian clock system. (2003) Genes and Development, August , 17(15), 1921-1932
2. Gorbacheva V.Y., Kondratov R.V., Zhang R., Gudkov A.V., Takahashi J.S., and Antoch M.P. Circadian control of drug response: mouse sensitivity to chemotherapeutic drug cyclophosphamide is modulated by the functional status of CLOCK/BMAL1 transactivation complex. (2005) Proceedings of the National Academy of Sciences of U.S.A., 102(9), 3407-3412
3. Kondratov R.V.*, Kanagal R., Kondratova A.A., Gorbacheva V. Y., and Antoch M. P. Dual role of CLOCK/BMAL1 transcriptional complex in the transcription control. (2006) FASEB J. 20(3), 530-532
4. Kondratov R.V.*, Kondratova A.A., Lee C., Gorbacheva V.Y., Chernov M.V., and Antoch M.P. Posttranslational regulation of circadian CLOCK(NPAS2)/BMAL1 complex by CRYPTOCHROMES. (2006), Cell Cycle 5(8), 890-895
5. Kondratov R.V.*, Kondratova A.A., Gorbacheva V.Y., Vykhovanetc O.V. and Antoch M.P. Early aging and age-related pathologies in mice deficient in BMAL1, the core component of the circadian clock. (2006), Genes and Development, 20(14), 1868-1873
6. Kondratov R.V.*, Gorbacheva V.Y., Antoch M.P. Circadian proteins in normal physiology and genotoxic stress response. (2006), Current Topics in Developmental Biology, In Press, Invited Review.
* - Corresponding author