Shih
Shou-Ching S. Jaminet, Ph.D.
Director of Multi-Gene Transcriptional Profiling
Instructor of Pathology
Beth Israel Deaconess Medical Center
Harvard Medical School

330 Brookline Avenue, RN-280D
Boston, MA 02215
Office: 617-667-8156
Fax: 617-667-3591
Email:
sjaminet@bidmc.harvard.edu

Education/Training/Appointments:

Shou-Ching S. Jaminet earned her Ph.D in Cancer Immunology from Newcastle University, Newcastle, Australia in 1994. After post-doctoral research at Sloan Kettering Cancer Center, she became an Instructor at Boston Children's Hospital, in 2000. She joined BIDMC in 2005, where she established and leads the Multi-Gene Transcriptional Profiling Laboratory.


Research Interests: Intercellular Communication and Angiogenesis

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Basic Research - My research is based upon the view that the quantity of a transcribed product determines a gene's biological effect, and that per-cell quantities of mRNAs provide the best window into molecular networks. To implement a transcriptome-based research strategy, my lab developed Multi-Gene Transcriptional Profiling (MGTP), a method for measuring mRNA copy numbers per cell of multi-gene panels. Through MGTP, we identified TM4SF1 as a new endothelial cell biomarker and a new anti-angiogenic therapeutic target.


I am currently pursuing the hypothesis that TM4SF1 is an endocytic vehicle that delivers cargos to the nucleus of endothelial cells for the regulation of proliferation, migration, and intercellular interactions. Studies currently underway include:

1. Investigation of TMED internalization mechanisms and identification of cargo proteins of TMED. We have currently identified β-actin, myosin-10, dynamin, tubulin, PLCγ, HDAC6, and ERG as TM4SF1 interaction partners. PLCγ is an immediate downstream mediator of VEGF-A signaling.

2. Evaluation of TM4SF1 as a therapeutic target for solid tumors. TM4SF1 is a uniquely attractive therapeutic target due to (a) its high expression in tumor vessels and tumor cells, but low expression in normal vessels and other normal cell types, and (b) its ability via endocytosis to deliver antibody-drug conjugates to the cytosol and nucleus. We are currently working with a major pharmaceutical company to develop an anti-TM4SF1 antibody drug conjugate cancer therapy.

3. Role of TM4SF1 in intercellular interactions and vasculogenesis. TM4SF1 regulates endothelial cell intercellular interactions through formation of nanopodia, long (up to 50 μm) and thin (~100-300 nm) membrane extensions that anchor to the extracellular matrix through intermittent TMED (Figure 1A, green arrows) and can form intercellular nanotubes that become the sites of junctions. TM4SF1 heterozygous mice are developmentally delayed and 50% die in utero or perinatally of brain hemorrhage. TM4SF1-het mice thus provide a unique model in which to study the role of TM4SF1 in vasculogenesis.

4. Genetic variants. A variety of TM4SF1 single nucleotide polymorphisms (SNPs) are known to occur in humans, and we are investigating their roles in TMED endocytosis and their possible clinical relevance in cancer and other diseases.


New and Noteworthy Publications:

Lin, C.I., Merley, A., Sciuto, T.E., Li, D., Melero-Martin, J.M., Dvorak, A.M., Dvorak, H.F. & Jaminet, S.C. TM4SF1: a new vascular therapeutic target in cancer. Angiogenesis in press (2014). PMID: 24986520

Lin, C.I., Lau, C.Y., Li, D. & Jaminet, S.C. Nanopodia--thin, fragile membrane projections with roles in cell movement and intercellular interactions. Journal of visualized experiments : JoVE, e51320 (2014). PMID: 24747485

Zukauskas, A., Merley, A., Li, D., Ang, L.H., Sciuto, T.E., Salman, S., Dvorak, A.M., Dvorak, H.F. & Jaminet, S.C. TM4SF1: a tetraspanin-like protein necessary for nanopodia formation and endothelial cell migration. Angiogenesis 14, 345-354 (2011). Selected for cover art. PMID: 21626280.

Wada, Y., Li, D., Merley, A., Zukauskas, A., Aird, W.C., Dvorak, H.F. & Shih, S.C. A multi-gene transcriptional profiling approach to the discovery of cell signature markers. Cytotechnology 63, 25-33 (2010). PMID: 20972619

Shih, S.C., Zukauskas, A., Li, D., Liu, G., Ang, L.H., Nagy, J.A., Brown, L.F. & Dvorak, H.F. The L6 protein TM4SF1 is critical for endothelial cell function and tumor angiogenesis. Cancer Res 69, 3272-3277 (2009). Corresponding author. PMID: 19351819.