Welcome to the Lab of Shou-Ching Jaminet, Ph.D.

The home of TM4SF1 (Transmembrane-4-L-six-family)

Shou-Ching Jaminet

(史守卿)

Beth Israel Deaconess Medical Center

Harvard Medical School

Director, Multi-Gene Transcriptional Profiling Core

National Taiwan University (BS,MS)

Newcastle University, Australia (PhD)

I am a vascular biologist specializing in the study of tumor angiogenesis. I base much of my research on the view that the quantity of transcribed mRNA is the best indicator of a gene’s biological significance, and that multi-gene profiles showing per-cell quantities of mRNAs provide an informative window into the state of molecular networks.

To implement such a transcriptome-based research strategy, my lab developed Multi- Gene Transcriptional Profiling (MGTP), a method for efficiently and precisely measuring mRNA copy numbers per cell mRNA copy numbers per cell of multi-gene panels. Through MGTP, my group identified TM4SF1 as a new endothelial cell biomarker and a novel anti-angiogenic therapeutic target.

Before my group showed that TM4SF1 is an essential regulator of endothelial cell movement and proliferation, TM4SF1 was known only as a tumor cell antigen of tetraspanin topology; only 53 publications mentioning TM4SF1 had appeared through 2005.


We have now shown that:

• TM4SF1 is a new endothelial cell biomarker and is an essential regulator of endothelial cell movement and proliferation in vitro and vessel maturation in vivo.
• TM4SF1 is highly expressed in proliferating endothelial cells, a large variety of cultured tumor cells, and bone marrow derived mesenchymal stem cells, but weakly or not expressed by other cell types.
• TM4SF1 forms 100-300 nm diameter TM4SF1-enriched domains (TMED) on cell surface and each TMED contain three to fourteen TM4SF1 molecules.
  
• On the abluminal side of the cell surface, TMED firmly attach to matrix and assist nanopodia formation, a thin, fragile membrane projections with roles in cell movement and intercellular interactions.
• TM4SF1 is internalized from the cell surface in a clathrin independent manner, travels to the perinuclear region along microtubules, and subsequently enters the nucleus through nuclear pores (paper in preparation).
• TM4SF1-knockout mice are embryonically lethal at day-9 due to a failure of vasculogenesis (paper in preparation).
• TM4SF1 is a new vascular therapeutic target in cancer.