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Shou Ching Shih Lab

Multi-gene transcriptional profiling (MGTP). MGTP is a quantitative profiling technique based on real-time PCR (Am. J. Pathol 2002; Mol Exp Path 2005). It is a sensitive, high-throughput approach to tissue fingerprinting, and offers a systems approach to the discovery of biomarkers and the study of molecular mechanisms. Currently, our transcriptional profiling lab has primer sets for over 800 human and murine genes and we are adding about 50 genes per month. We collaborate with a number of researchers from a variety of institutions in order to more widely share the benefits of our technique and primer library.

Tumor signatures and early detection of cancer. We are using MGTP to survey expression from over 300 growth factor/cytokine genes in order to identify tumor signatures. One goal of this research is to find highly expressed tumor biomarkers which have soluble forms. Such soluble biomarkers may be detected in serum or urine and could lead to routine tests for early detection of cancer. Many of these soluble factors play coordinating roles in angiogenesis and are potential drug targets. This research also aims to elucidate the roles of growth factors/cytokines in the tumor micro-environment and angiogenesis.

Angiogenesis and vessel survival. Our research has focused on the fundamental gene-protein networks underlying blood vessel formation and degeneration in pathological angiogenesis, using the murine retina and tumors as in vivo models. Using transcriptional profiling techniques, we uncovered the importance of VEGFR-1 in blood vessel survival (J Clin Invest 2003), the critical role of pericyte-derived TGF-ß in VEGFR-1 signaling (PNAS 2003), and identified ninety-three new vascular markers (in preparation). Using MGTP, we are currently investigating the molecular mechanisms involved in vessel survival.

Selected Recent Publications

Adam, R.M., Eaton, S.H., Estrada, C., Nimgaonkar, A., Shih, S.C., Smith, L.E., Kohane, I.S., Bagli, D., Freeman, M.R. 2004. Mechanical Stretch is a Highly Selective Regulator of Gene Expression in Human Bladder Smooth Muscle Cells. Physiol Genomics, in press.

Agarwal, A., Estrada-Hernandez, T., Kleuh, U., Shih, S.C., and Claffey, K.P. 2004. N-Acetyl-Cysteine Promotes Angiostatin Production and Tumor Vascular Depletion in a VEGF Dependent Manner. Am J Pathol 164:1683-1696.

Shih, S.C. and Smith L.E. 2005. Quantitative Multi-Gene Transcriptional Profiling using Real-time PCR with a Master Template. Experimental and Molecular Pathology, in press.

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