My laboratory is interested in functional genomics approaches to discovering gene programs that experimentally regulate and clinically predict cancer metastasis and its resistance to treatment.
KEYWORDS: Metastasis, chemotherapy resistance, radiation resistance, DNA damage, breast cancer, glioblastoma multiforme, bioinformatics, genomics, microRNA, STAT1, interferon.
The two most daunting obstacles in the clinical management of cancer are metastasis, or the spread of tumor cells from its origin to distant sites in the body, and resistance to chemotherapy and/or radiation, which are two primary means of treating the disease. Unfortunately, the molecular mechanisms that drive these central and elusive problems in oncology have remained poorly understood.
Our laboratory is focused on understanding how cancer cells acquire metastatic and treatment resistant phenotypes. Recent evidence suggests that these two traits are acquired during tumorigenesis by antagonistic forces encountered as tumors grow and interact with their environment. Key among these selective pressures include inflammation, overcoming senescence and apoptosis, and barriers imposed by surrounding stroma. Because the biology of these selective pressures can overlap with molecular mechanisms involved in metastasis and treatment resistance, genetic alterations that occur as a response to these pressures may predispose tumors to acquire a metastatic and/or treatment-resistant phenotype.
In order to better understand the basis for metastasis and treatment resistance, we utilize a multi-disciplinary approach towards both experimental and translational research goals. Hypothesis generation and testing relies on a systems biology paradigm that incorporates animal models, molecular biology, functional genomics, bioinformatics, and clinical correlation. Using these methods we and colleagues have identified gene expression signatures and signaling pathways that not only predict but also regulate cancer phenotypes such as aggressive organ-selective metastasis and resistance to DNA damaging agents (chemotherapy and radiation). Some of these signatures and pathways are expressed across multiple common human cancers including breast and brain cancer. Genes that regulate the expression or function of the signatures include microRNAs, interferon-related genes, and ubiquitin modifiers. Thus, gene signatures and the signaling pathways that control them point toward relevant biology that can be dissected and provide clinical tools for prognosis, prediction, and potential therapeutic targeting.
Many rotation projects related to the research interests described are available. Please contact Dr. Minn to inquire.
Taewon Yoon, Postdoctoral researcher
Yu Qiu, Postdoctoral researcher
Danielle Loughlin, Postdoctoral researcher
Christina Twyman, Fellow
Tony Wu, Research specialist
Bihui Xu, Graduate student
Barzin Nabet, Graduate student
Erik Clarke, Rotation student
Ishwaran H, Kogalur UB, Chen X, Minn AJ : Random survival forests for high-dimensional data. Statistical Analysis and Data Mining 4: 115-32, Jan 2011.
Ishwaran H, Kogalur UB, Gorodeski EZ, Minn AJ, Lauer MS: High dimensional variable selection for survival data. Journal of the American Statistical Association 105: 205-17, Mar 2010.
Bos PD, Zhang XH, Nadal C, Shu W, Gomis RR, Nguyen DX, Minn AJ, van de Vijver MJ, Gerald WL, Foekens JA, Massagué J: Genes that mediate breast cancer metastasis to the brain. Nature. 459(7249): 1005-9, Jun 2009.
Dangi-Garimella S, Yun J, Eves EM, Newman M, Erkeland SJ, Hammond SM, Minn AJ, Rosner MR: Raf kinase inhibitory protein suppresses a metastasis signalling cascade involving LIN28 and let-7. EMBO J. 28(4): 347-58, Feb 2009.
Weichselbaum RR, Ishwaran H, Yoon T, Nuyten DS, Baker SW, Khodarev N, Su AW, Shaikh AY, Roach P, Kreike B, Roizman B, Bergh J, Pawitan Y, van de Vijver MJ, Minn AJ: An interferon-related gene signature for DNA damage resistance is a predictive marker for chemotherapy and radiation for breast cancer. Proc Natl Acad Sci U S A 105(47): 18490-5, Nov 2008.
Khodarev NN, Minn AJ, Efimova EV, Darga TE, Labay E, Beckett M, Mauceri HJ, Roizman B, Weichselbaum RR: Signal transducer and activator of transcription 1 regulates both cytotoxic and prosurvival functions in tumor cells. Cancer Res. 67(19): 9214-20, Oct 1 2007.
Minn AJ, Gupta GP, Padua D, Bos P, Nguyen DX, Nuyten D, Kreike B, Zhang Y, Wang Y, Ishwaran H, Foekens JA, van de Vijver M, Massagué J: Lung metastasis genes couple breast tumor size and metastatic spread. Proc Natl Acad Sci U S A 104(16): 6740-5, Apr 2007.
Minn AJ, Gupta GP, Siegel PM, Bos PD, Shu W, Giri DD, Viale A, Olshen AB, Gerald WL, Massagué J: Genes that mediate breast cancer metastasis to lung. Nature. 436(7050): 518-24, Jul 28 2005.
Minn AJ, Kang Y, Serganova I, Gupta GP, Giri DD, Doubrovin M, Ponomarev V, Gerald WL, Blasberg R, Massagué J.: Distinct organ-specific metastatic potential of individual breast cancer cells and primary tumors. J Clin Invest. 115(1): 44-55, Jan 2005.
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Last updated: 02/27/2014
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