Lubomir B. Smilenov, Ph.D.

Center for Radiological Research           Email: lbs5@columbia.edu
630 West 168th Street, VC 11-204        Tel: 212-305-5661
New York, N.Y. 10032                                Fax: 212-305-3229  

   Current Academic and Professional Appointments  

• Assistant Professor, Department of Radiation Oncology, Center for Radiological Research, College of Physicians & Surgeons, Columbia University

   Research Highlights  

Project 1.  Role of heterozygosity for DNA repair genes in radiation response and radiation sensitivity 

Loss of function of DNA repair genes has been implicated in the development of many types of cancer, but for the vast majority of cases there is no link to specific germline mutations. In the last several years heterozygosity leading to haploinsufficiency for proteins involved in DNA repair pathways was shown to play a role in genomic instability and carcinogenesis after DNA damage is induced. Since the effect of heterozygosity for one protein is relatively small, we hypothesize that predisposition to cancer could be a result of the additive effect of heterozygosity for two or more genes critical to pathways that control DNA damage signaling, repair or apoptosis. We investigated the role of heterozygosity for Atm, Rad9 and Brca1 on cell transformation, apoptosis and cataractogenesis. Our results show that cells heterozygous for both Atm and Rad9 or Atm and Brca1 are more resistant to apoptosis are more sensitive to transformation by radiation when compared with wild-type controls or those cells haploinsufficient for only one of these proteins. Radiation induced cataractogenesis also depends on the genotype and at least for Atm and Rad9 genes is enhanced by combined haploinsufficiency for both genes.

Project 2. Role of miRNAs in radiation response

miRNA has recently emerged as an important regulator of gene expression, possibly regulating as many as one-third of all human genes. Despite some progress, the characterization of miRNA-related mechanisms is still in its initial stage. Our current works shows that significant changes in miRNA expression occurs after irradiation of normal human cells. These differences assign important regulatory functions for miRNA expressed in irradiated cells. The main hypothesis of our study is that miRNA expression will very specifically reflect the type and dose of radiation, and that the combination of miRNA and gene expression profiling will characterize radiation responses even better. The integration of miRNA and gene expression analysis will definitely increase our understanding of the mechanisms involved in the cellular response to stress. The studies, which build from cell models to mouse models to whole human blood, represent a comprehensive set of experiments that will allow us to build on results from each stage. The integrated interpretation of these results is intended to accelerate our understanding of the signaling mechanisms involved in the response to ionizing radiation in general, and to protons and HZE particles specifically, and to facilitate discovery of new biomarkers for biodosimetry.

   Select Publications Online  

Some papers are available online in PDF format (requires Adobe Acrobat Reader, available for free download here: )

If you do not find what you are looking for below, try searching for Lubomir Smilenov on PubMed.

• Kleiman NJ, David J, Elliston CD, Hopkins KM, Smilenov LB, Brenner DJ, Worgul BV, Hall EJ and Lieberman HB. Mrad9 and atm haploinsufficiency enhance spontaneous and X-ray-induced cataractogenesis in mice. Radiat Res. 168(5):567-73, 2007. [abstract]

• Schwartz EI, Smilenov LB, Price MA, Osredkar T, Baker RA, Ghosh S, Shi FD, Vollmer TL, Lencinas A, Stearns DM, Gorospe M and Kruman II. Cell cycle activation in postmitotic neurons is essential for DNA repair. Cell Cycle 6(3):318-29, 2007. [abstract]

• Xu A, Smilenov LB, He P, Masumura K, Nohmi T, Yu Z and Hei TK. New insight into intrachromosomal deletions induced by chrysotile in the gpt delta transgenic mutation assay. Environ Health Perspect 115(1):87-92, 2007. [abstract]

• Hall EJ, Worgul BV, Smilenov L, Elliston CD and Brenner DJ. The relative biological effectiveness of densely ionizing heavy-ion radiation for inducing ocular cataracts in wild type versus mice heterozygous for the ATM gene. Radiat Environ Biophys. 45(2):99-104, 2006. [abstract]

• Smilenov LB. Tumor development: Haploinsufficiency and local network assembly. Cancer Lett. 240(1):17-28, 2006. [abstract][PDF]

• Sokolov MV, Smilenov LB, Hall EJ, Panyutin IG, Bonner WM and Sedelnikova OA. Ionizing radiation induces DNA double-strand breaks in bystander primary human fibroblasts. Oncogene 24(49):7257-65, 2005. [abstract]

• Worgul BV, Smilenov L, Brenner DJ, Vazquez M and Hall EJ. Mice heterozygous for the ATM gene are more sensitive to both X-ray and heavy ion exposure than are wildtypes. Adv Space Res. 35(2):254-9, 2005. [abstract]

• Hall EJ, Brenner DJ, Worgul B and Smilenov L. Genetic susceptibility to radiation. Adv Space Res. 35(2):249-53, 2005. [abstract]

• Smilenov LB, Lieberman HB, Mitchell SA, Baker RA, Hopkins KM and Hall EJ. Combined haploinsufficiency for ATM and RAD9 as a factor in cell transformation, apoptosis, and DNA lesion repair dynamics. Cancer Res 65(3):933-8, 2005. [abstract][PDF]

• Kruman II, Wersto RP, Cardozo-Pelaez F, Smilenov L, Chan SL, Chrest FJ, Emokpae R Jr, Gorospe M and Mattson MP. Cell cycle activation linked to neuronal cell death initiated by DNA damage. Neuron 41(4):549-61, 2004. [abstract]

• Worgul BV, Smilenov L, Brenner DJ, Junk A, Zhou W and Hall EJ. Atm heterozygous mice are more sensitive to radiation-induced cataracts than are their wild-type counterparts. Proc Natl Acad Sci U S A 99(15):9836-9, 2002. [abstract]

• Schmeissner PJ, Xie H, Smilenov LB, Shu F and Marcantonio EE. Integrin functions play a key role in the differentiation of thymocytes in vivo. J Immunol. 167(7):3715-24, 2001. [abstract]

• Smilenov LB, Brenner DJ and Hall EJ. Modest increased sensitivity to radiation oncogenesis in ATM heterozygous versus wild-type mammalian cells. Cancer Res. 61(15):5710-3, 2001. [abstract][PDF]

• Smilenov LB, Michailov A, Marcantonio E and Gundersen G. Focal adhesion motility revealed in stationary fibroblasts. Science 286(5442):1172-4, 1999. [abstract][PDF]