The Selected Cell Epigenomic Analysis Core will support Center Research projects by enabling molecular analysis that reach beyond the ensemble measurements that conventionally limit studies derived from averages over large numbers of cells. We will harness and advance the technologies derived from engineering and physical science to isolate and observe selected cells and their interaction with and response to environmental factors. Each Center research project will identify and characterize particular tumor cell phenotypes usually in rare subpopulations. The Core will develop processes and devices to rapidly evaluate the molecular state of selected cells and work toward analysis of a few or even individual cells. The Core will enable Center reserchers to understand the distribution'of properties and to then consider the consequences of this heterogeneity in the context of various microenvironments. Such analyses should lead to a more fundamental understanding of cancer. In this core activity we will design a fluidic network to perform sample preparation on chip. This will include a chip-based cell sorter for selecting labeled cells of interest. These will be sorted and delivered to on-chip chambers for cell lysing and extraction of whole genomic DNA from cellular nuclei. We will design a network of microfluidic compartments using methods described in the microfabrication core. The goal will be to extract, retain and efficiently deliver DNA for analysis without the need for PCR amplification. Initially this will be done with many cells for delivery of sample to existing Chip-seq and DNA methylation analyses. As the concepts for analysis are verified, the sample preparation process will be extended to deliver material to separately developing single molecule approaches.
This PS-OC brings together expert teams from the fields of physics, nano and microfabrication, engineering and cancer biology to develop novel trans-disciplinary approaches to better understand the complexity of cancer metastasis, the aspect of cancer that directly leads to patient morbidity and mortality. Approaches developed by physical scientists will be focused on the study of cancer. Our studies aim to identify novel mechanisms used by cancer cells, but not normal cells, for growth and metastasis to distant body sites. These new mechanism provide novel drug targets, that aim towards arresting cancer metastasis.
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|Seigel, Gail M (2014) Review: R28 retinal precursor cells: the first 20 years. Mol Vis 20:301-6|
|Hughes, Andrew D; Marshall, Jocelyn R; Keller, Eric et al. (2014) Differential drug responses of circulating tumor cells within patient blood. Cancer Lett 352:28-35|
|Mitchell, Michael J; King, Michael R (2014) Unnatural killer cells to prevent bloodborne metastasis: inspiration from biology and engineering. Expert Rev Anticancer Ther 14:641-4|
|Rhim, Andrew D; Thege, Fredrik I; Santana, Steven M et al. (2014) Detection of circulating pancreas epithelial cells in patients with pancreatic cystic lesions. Gastroenterology 146:647-51|
|Esch, Mandy B; Smith, Alec S T; Prot, Jean-Matthieu et al. (2014) How multi-organ microdevices can help foster drug development. Adv Drug Deliv Rev 69-70:158-69|
|Chandrasekaran, Siddarth; Marshall, Jocelyn R; Messing, James A et al. (2014) TRAIL-mediated apoptosis in breast cancer cells cultured as 3D spheroids. PLoS One 9:e111487|
|Santana, Steven M; Antonyak, Marc A; Cerione, Richard A et al. (2014) Microfluidic isolation of cancer-cell-derived microvesicles from hetergeneous extracellular shed vesicle populations. Biomed Microdevices 16:869-77|
|Congleton, Johanna; Shen, Miaoqing; MacDonald, Robert et al. (2014) Phosphorylation of c-Cbl and p85 PI3K driven by all-trans retinoic acid and CD38 depends on Lyn kinase activity. Cell Signal 26:1589-97|
|Thadani-Mulero, Maria; Portella, Luigi; Sun, Shihua et al. (2014) Androgen receptor splice variants determine taxane sensitivity in prostate cancer. Cancer Res 74:2270-82|
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