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 Cancer is a complex genetic disease that results from a combination of genetic and environmental perturbations to biomolecular networks that typically maintain a homeostatic balance between normal cellular functional states, such as proliferation, apoptosis, and differentiation. Using genome-wide genomic and proteomic measurements of cancer cells (primary tumors, distant metastases, cell lines treated with chemotherapeutic drugs, etc.), coupled with computational approaches, we can gain insights into cellular dysfunction underlying cancer onset, progression, and metastasis.
 At the same time, accurate and early diagnostic markers are critical to the prevention and treatment of cancers. Genome-wide measurements of cancer tissues, combined with statistical pattern recognition and machine learning approaches, allow us to determine sets of informative genes or proteins whose measurements may be used for prognosis or diagnosis. Examples include; distinguishing subtypes or different stages of a cancer, determining whether a cancer has metastatic potential, predicting survival or the likelihood of a successful response to a therapy.
Publications:
L. Hu, W. Hittelman, T. Lu, P. Ji, R. Arlinghaus, I. Shmulevich, S. R. Hamilton, W. Zhang, "NGAL decreases E-cadherin-mediated cell-cell adhesion and increases cell motility and invasion through Rac1 in colon carcinoma cells," Laboratory Investigation, Vol. 89, pp. 531–548, 2009.
N. D. Price, J. Trent, A. K. El-Naggar, D. Cogdell, E. Taylor, K. K. Hunt, R. E. Pollock, L. Hood, I. Shmulevich, W. Zhang, “Highly accurate two-gene classifier for differentiating gastrointestinal stromal tumors and leiomyosarcomas,” Proceedings of the National Academy of Sciences of the USA, Vol. 104, No. 9, pp- 3414-3419, 2007.
R. Jiang, C. Mircean, I. Shmulevich, D. Cogdell, Y. Jia, I. Tabus, K. Aldape, R. Sawaya, J. M. Bruner, G. N. Fuller, W. Zhang, “Pathway alterations during glioma progression revealed by reverse phase protein lysate arrays,” Proteomics, Vol. 6, pp. 2964-2971, 2006.
M. Nykter, K. K. Hunt, R. E. Pollock, A. K. El-Naggar, E. Taylor, I. Shmulevich, O. Yli-Harja, W. Zhang, “Unsupervised analysis uncovers changes in histopathologic diagnosis in supervised genomic studies,” Technology in Cancer Research and Treatment, Vol. 5, No. 2, pp. 177-182, 2006.
H. Lähdesmäki, I. Shmulevich, V. Dunmire, O. Yli-Harja, W. Zhang, "In Silico Microdissection of Microarray Data from Heterogeneous Cell Populations," BMC Bioinformatics 6:54, 2005.
G. N. Fuller, C. Mircean, I. Tabus, E. Taylor, R. Sawaya, J. M. Bruner, I. Shmulevich, W. Zhang, "Molecular voting for glioma classification reflecting heterogeneity in the continuum of cancer progression," Oncology Reports, Vol. 14, pp. 651-656, 2005.
E. Lee, C. Mircean, I. Shmulevich, H. Wang, J. Liu, A. Niemistö, J. Kavanagh, JH Lee, W. Zhang, "Insulin-like growth factor binding protein 2 promotes ovarian cancer cell invasion" Molecular Cancer, Feb 02;4(1):7, 2005.
H. Lähdesmäki, X. Hao, B. Sun, L. Hu, O. Yli-Harja, I. Shmulevich, and W. Zhang, "Distinguishing key biological pathways between primary breast cancers and their lymph node metastases by gene function-based clustering analysis," International Journal of Oncology, Vol. 24, No. 6, pp. 1589–1596, June 2004.
X. Hao, B. Sun, L. Hu, H. Lähdesmäki, V. Dunmire, Y. Feng, S.-W. Zhang, H. Wang, C. Wu, H. Wang, G. N. Fuller, W. F. Symmans, I. Shmulevich, and W. Zhang, "Differential gene and protein expression in primary breast malignancies and their lymph node metastases as revealed by combined cDNA microarray and tissue microarray analysis," Cancer, Vol. 100, No. 6, pp. 1110-1122, 2004.
C. Mircean, I. Tabus, T. Kobayashi, M. Yamaguchi, H. Shiku, I. Shmulevich, W. Zhang, "Pathway Analysis of Informative Genes from Microarray Data Reveals that Metabolism and Signal Transduction Genes Distinguish Different Subtypes of Lymphomas," International Journal of Oncology, Vol. 24, No. 3, pp. 497-504, 2004.
J. Morikawa, H. Li, S. Kim, K. Nishi, S. Ueno, E. Suh, E. Dougherty, I. Shmulevich, H. Shiku, W. Zhang, and T. Kobayashi, "Identification of signature genes by microarray for acute myeloid leukemia without maturation and acute promyelocytic leukemia with t(15;17)(q22;q12)(PML/RARa)," International Journal of Oncology, Vol. 23, No. 3, pp. 617-625, 2003.
T. Kobayashi, M. Yamaguchi, S. Kim, J. Morikawa, S. Ogawa, S. Ueno, E. Suh, E. Dougherty, I. Shmulevich, H. Shiku, W. Zhang, "Microarray Reveals Differences in Both Tumors and Vascular Specific Gene Expression in De Novo CD5+ and CD5- Diffuse Large B-cell Lymphomas," Cancer Research, vol. 63, pp. 60-66, January 2003.
S. Kim, E. R. Dougherty, I. Shmulevich, K. R. Hess, S. R. Hamilton, J. M. Trent, G. N. Fuller, W. Zhang, "Identification of Combination Gene Sets for Glioma Classification," Molecular Cancer Therapeutics, vol. 1, pp. 1229-1236, November 2002.
I. Shmulevich, K. Hunt, A. El-Naggar, E. Taylor, L. Ramdas, P. Labordé, K. R. Hess, R. Pollock, W. Zhang, "Tumor Specific Gene Expression Profiles in Human Leiomyosarcoma: an Evaluation of Intra-Tumor Heterogeneity," Cancer, Vol. 94, No. 7, pp. 2069-2075, 2002.
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