Cell-cell adhesion in stem cell fate decisions and tissue regeneration

Andreadis Research Group

bio imaging images of Cadherin 11 cells.

The Andreadis research group aims to understand the fundamental mechanobiology of cell adhesion in stem cell fate decisions, tissue regeneration and cancer metastasis.

Overview

Cadherin-11 is a classical type II cadherin which is known as a calcium-dependent trans-membrane adhesion protein. Cadherins play critical roles in cell adhesion by forming hemophilic junctions binding cells together within tissues and maintaining tissue integrity. More recently, cadherins have also been implicated in signal transduction.

The Andreadis group implicated cadherin-11 in MSC (mesenchymal stem cell) differentiation into SMC (smooth muscle cell) via ROCK pathway (1, 2). Subsequently, Yayu Liu a PhD candidate and Dr. Sinhu Row, who recently graduated from the UB CBE PhD program reported that cadherin-11 is necessary for extracellular matrix synthesis e.g. collagen and elastin, both in vivo and in vitro ultimately controlling the tissue’s mechanical properties (3). More recently, Yayu Liu and Dr. Pedro Lei discovered that cadherin-11 interacts with PDGFRb (platelet-derived growth factor receptor beta) to regulate cell proliferation via the AKT pathway. Furthermore, in vivo experiments with cadherin 11-/- (KO) mice showed that cadherin-11 is necessary for wound healing and tissue regeneration. These results provide mechanistic understanding of the role of cadherin-11 in cell proliferation even when growth factors are present at very low concentrations, implicating this cadherin in tumor growth and metastasis.

Students on this Project

  • Yayu Liu (PhD Candidate)
  • Sindhu Row (PhD)
  • Pedro Lei (PhD)

Resulting publications

  1. Alimperti S, Andreadis ST. CDH2 and CDH11 act as regulators of stem cell fate decisions. Stem Cell Res. 2015 May; 14(3):270-82.
  2. Alimperti S, You H, George T, Agarwal SK, Andreadis ST. Cadherin-11 regulates both mesenchymal stem cell differentiation into smooth muscle cells and the development of contractile function in vivo. J Cell Sci. 2014 Jun 15; 127(12):2627-38.
  3.  Row S, Liu Y, Alimperti S, Agarwal SK, Andreadis ST. Cadherin-11 is a novel regulator of extracellular matrix synthesis and tissue mechanics. J Cell Sci. 2016 Aug 1;129(15):2950-61.