Cancer Stem Cell Research Laboratory
Director: Galina Botchkina, PhD.
Key Words: Cancer; Stem cells; Genomics; Anti-Cancer Drug Development.
During the last 55 years, cancer has moved from the category of invariably fatal to the category of chronic diseases. However, metastatic epithelial cancers remain to be incurable by standard treatment modalities. This failure was attributed to the existence of rare, highly drug- and radiation-resistant cells within the tumor, a hypothesis which was firmly confirmed by the recent discovery of tumor-initiating cells with stem-like properties, called cancer stem cells (CSCs), in all major types of human cancers. This discovery has dramatically improved our understanding of tumor development and made clear the necessity to develop novel effective therapies targeting these exceptionally resistant cells.
Current research in my laboratory is focused on studying the prostate and colon tumor-initiating CSCs and CSC-targeted anti-cancer drug development. We have obtained the biologic and genomic CSC characteristics, and developed 3D in vitro CSC culture systems, which are more relevant both clinically and with respect to stem cell biology. The CSC-focused research and CSC-targeted drug development is widely accepted as a new concept of carcinogenesis and new paradigm of cancer treatment strategies. We investigate CSC-targeted activities of several new-generation taxoids against prostate and colon CSCs. We have identified several members of this family which significantly affect a stemness state of the prostate and colon CSCs (Botchkina et al., 2010). Our experience in stem cell research and accumulated data allow for fruitful collaboration on many aspects of tumor and stem cell biology. Current research is supported by NIH and NYSTAR grants.
I. Cancer Stem Cells
We have identified several candidate phenotypic populations of the tumor-initiating cells and obtained their genome-wide and pathway-specific characteristics (Rowehl et al., 2008; Botchkina et al., 09; Song et al., 09; Botchkina et al., 2010). We have developed 3D in vitro CSC culture systems, which are more clinically relevant, as well as more relevant to the stem cell biology. Our experience in stem cell research and accumulated data allow for fruitful collaboration on many aspects of the tumor and stem cell biology.
II. CSC-Targeted Drug Development
At the present time, metastatic epithelial cancers remain incurable, which is related to the exceptional resistance of CSCs to standard therapies. The CSC-focused research and CSC-targeted drug development is widely accepted as a new concept of carcinogenesis and new paradigm of cancer treatment strategies. We investigate CSC-targeted activities of several new-generation taxoids against prostate and colon CSCs. We have identified several members of this family which significantly affect a stemness state of the prostate and colon CSCs (Botchkina et al., 2010).
III. Development of the Bench-top Instruments for Early Cancer Detection
My long-term collaboration with the Department of Electrical & Computer Engineering, Sensor CAT (Serge Luryi and Vera Gorfinkel) and BioPhotonics Inc. resulted in the development of the two novel technologies for early cancer detection and analysis, the SBU Telomerase Analyzer and the Integrated Real-Time PCR/Capillary Electrophoresis System funded by two NIH SBIR/STTR (R42CA106193-04 and R43CA113188-01) and 3 NYSTAR grants.
IV. Mathematic modeling of the stem cell proliferation and responses to drugs
In collaboration with the Department of Electrical & Computer Engineering (Petar Djuric and Monica Bugallo), and Applied Mathematics Inc. (Lev Ginzburg and Nicholas Friedenberg) we are working on mathematical modeling of stem cell proliferation, signal processing, and responses to drugs. We have submitted 3 NSF proposals. One SBIR/STTR proposal will be submitted in April.
1. Botchkina GI, Kim RH, Botchkina IL, Kirshenbaum A, Frischer ZI and Adler HL.Noninvasive detection of prostate cancer by quantitative analysis of telomerase activity. Clinical Cancer Research, 11 (9), 3243-3249, 2005.
2. KabotyanskiEA, BotchkinaIL, KosobokovaO, BotchkinaGI, GorfinkelV, and GorbovitskiB. Highly sensitive revealing of PCR products with capillary electrophoresis based on single photon detection. Biosens Bioelectron., 21, 1924-1931, 2006.
3. Rowehl RH, Crawford H, Dufour A, Leyfman Y, J. Ju, and Botchkina GI. Genomic Analysis of Prostate Cancer Stem Cells Isolated from Highly Metastatic Cell Line. Cancer Genomics and Proteomics, 5(6), 301-309, 2008.
4. Botchkina IL, Rivadeneira D, Watkins K, Karpeh MS and Botchkina GI. Clinical Significance of Telomerase Activity in Peritoneal Disseminated Cells: Gastrointestinal Cancers. Molecular Medicine, 14 (1-2), 45-54, 2008.
5. Botchkina IL, Rowehl RA, Rivadeneira DE, Karpeh MS Jr, Crawford H, Dufour A, Ju J, Weng Y, Leyfman Y, and Botchkina GI. Phenotypic Subpopulations of Metastatic Colon Cancer Stem Cells: Genomic Analysis. Cancer Genomics and Proteomics, 6(1), 19-30, 2009.
6. Wang Y, Song B, Botchkina G, Gavin, E, Wan Y, Formentini A, Kornmann M, Ju J. miR-140 inhibits cell prolieferation by targeting histone deacetylase 4 in human colon and osteosarcoma cancer cells mediated by p53. Oncogene, 1-10, 2009.
7. Bugallo MF, Botchkina GI, Djuric PM. A stochastic model of proliferation of cancer stem cells and its estimation by particle filtering. ICASSP, 529-533, 2010.
8. BotchkinaGI, Wang Y, Savitt AG, Rowehl RA, Leyfman L, Wang H, Zhu S, Ju J, Zuniga E, Das M, and Ojima I. New-generation taxoid SB-T-1214 inhibits stem cell-related gene expression in three-dimensional cancer spheroids induced by two phenotypic subpopulations of colon tumor-initiating cells. Molecular Cancer 2010 (in press).
Galina I. Botchkina
Associate Professor of Pathology
Online Abstract System
Biochemistry & Cell Biology
Physiology & Biophysics
Molecular Genetics & Microbiology
Applied Mathematics and Statistics
Oral Biology and Pathology
Phone: 631.632.1311 * Fax: 631.632.7942 Email: email@example.com