Shou-Ching Shih, PhD
Instructor of Pathology
Beth Israel Deaconess Medical Center
Harvard Medical School
330 Brookline Avenue, RN 280D
Boston, MA 02215
Shou-Ching Shih earned her Ph.D in Cancer Immunology from Newcastle University, Newcastle, Australia in 1994. After post-doctoral research at Sloan Kettering Cancer Center and Beth Israel Deaconess Medical Center commencing in 1994 and 1996 respectively, she became an Instructor at The Childrens Hospital in 2000. She returned to BIDMC in 2004, joining the Pathology Department and the CVBR.
Intercellular Communication and Angiogenesis
My laboratory investigates the molecular and cellular mechanisms of endothelial cell (EC) membrane nanotubes in angiogenesis with special emphasis on EC-EC and EC-tumor cell interactions.
Nanotubes in EC communication
We have recently shown that TM4SF1 plays a critical role in EC filopodia and nanotube formation, and that these structures are channels for long-distance cell-cell communication which provide directional guidance for EC migration and help organize new vascular structures. We are currently investigating the cellular and molecular mechanisms linking TM4SF1, integrins, and cytoskeletal components during EC nanotube formation and EC-EC and EC-tumor cell interactions.
My translational research makes extensive use of multi-gene transcriptional profiling (MGTP), a technique we developed that is helpful in the discovery of biomarkers. Discovery of new disease biomarkers in accessible tissues such as blood has the potential to identify clinically important prognostic or diagnostic markers. We are currently focused on chronic lymphocytic leukemia (CLL) prognosis. Gene expression profiling approaches to CLL prognosis. CLL is the most common leukemia, and there is currently no prognostic marker capable of identifying which CLL patients will benefit from early treatment or which treatment will be most effective in an individual patient. Recent work by ourselves and others has shown that epigenetic regulation of gene expression is a key causal factor in CLL, and that the expression of the targets of existing CLL drugs varies dramatically from patient to patient; thus, gene expression profiling of B cells drawn from CLL patient blood has the potential both to distinguish varieties of the disease and to provide a reliable means of prognosis and prediction of response to treatment.
New and Noteworthy Publications
View all publications via PubMed >>
Shih SC, Zukauskas A, Li D, Liu G, Nagy J, Brown L, Dvorak H. (2008) The L6 protein TM4SF1 is critical for tumor angiogenesis, endothelial cell filopodia and nanotube formation, and for cytokinesis. Cancer Cell, in process.
This study describes the roles of TM4SF1 in endothelial cell communications, nanotube formation and tumor angiogenesis, and is the first to demonstrate a role of intercellular membrane nanotubes in providing guidance for endothelial cell migration and vascular maturation.
Shih SC, Smith LE. (2005) Quantitative multi-gene transcriptional profiling using real-time PCR with a master template. Exp Mol Pathol 79:14.
This study describes a novel master template approach for quantitative real-time PCR measurement, a technique which greatly improves the usefulness of transcriptional profiling by enabling the ready measurement of mRNA copy numbers per cell from multi-gene panels.
Shih SC, Ju M, Liu N, Mo JR, Ney JJ, Smith LE. (2003) Transforming growth factor beta1 induction of vascular endothelial growth factor receptor 1: mechanism of pericyte-induced vascular survival in vivo. Proc Natl Acad Sci USA 100:15859.
This study was the first to conclusively demonstrate that TGFb1 expressed by pericytes induces VEGFR-1 expression in endothelial cells and plays a critical role in vascular survival.
Shih SC, Ju M, Liu N, Smith LE. (2003) Selective stimulation of VEGFR-1 prevents oxygen-induced retinal vascular degeneration in retinopathy of prematurity. J Clin Invest 112:50.
This study was the first to demonstrate that activation of VEGFR-1 through PLGF triggers survival mechanisms that rescue the retina from vascular degeneration.
Shih SC, Robinson GS, Perruzzi CA, Calvo A, Desai K, Green JE, Ali IU, Smith LE, Senger DR. (2002) Molecular profiling of angiogenesis markers. Am J Pathol 161:35.
This study described for the first time the use of multi-gene expression profiles generated by quantitative real-time PCR for the discovery of cell specific biomarkers.