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Human TM4SF1 Protein Topology and Protein Domains

The two faces of TMED

  1. On an endothelial cell’s luminal (blood vessel) side, TMED act as a vehicle that takes on cargo and delivers it to the cytoplasmic and nuclear compartments for the refulation of proliferation and migration.
  2. On the abluminal (tissue) side, TMED interact with integrins and assist cell attachment to matrix and facilitates nanopodia formation for movement and intercellular communication.

I am currently pursuing the hypothesis that TM4SF1 is:

  1. an endocytic vehicle that delivers cargos to specific intracellular locations, largely the nucleus, for the regulation of proliferation and migration.
  2. a molecular facilitator that recruit molecules to TMED for intercellular interactions through nanopodia.
    Studies currently underway include investigations of TM4SF1 internalization mechanisms and identification of cargo proteins. We have so far identified fourteen signaling molecules as TM4SF1 cargo proteins.

Ongoing Translational Research:

  1. TM4SF1 is a uniquely attractive solid cancer therapeutic target due to (a) its ability to internalize to the cytosol and nucleus, and (b) its high expression in tumor vascular endothelial cells and tumor cells, but low expression in normal vascular endothelium and other normal cell types. We have developed anti-human TM4SF1 antibodies and our current focus is to evaluate TM4SF1 as a cancer therapeutic target.
  2. investigation of the effect of TM4SF1 single nucleotide polymorphisms on TM4SF1 endocytosis and clinical outcomes in cancer and hemorrhagic stroke.
  3. anti-TM4SF1-linker diagnostic imaging for use in solid cancer diagnosis, prognosis, and patient stratification or personalized medicine.