Current Research in the Gladden Lab

The Gladden lab uses combinations of protein biochemistry, cell culture and mouse models to study how cell polarity and adhesion regulate tissue organization.  The majority of our work focuses on the function of a junctional polarity complex composed of the tumor suppressor protein Merlin, and the polarity proteins Par3 and aPKC.  These three proteins interact at sites of cell:cell contact called adherens junctions when cells make their initial contact with neighboring cells.  The interaction of the junctional polarity complex with the adherens junction is a critical step in establishing cell polarity and organizing tissues.  New work from our lab and others indicates that the adherens junction proteins as well as the junctional polarity proteins undergo alterations in diverse cancer types.  Developing an understanding of the role(s) played by these proteins in cancer initiation or progression is a primary interest of our lab.

In addition to studying how cell polarity and adhesion contribute to pathogenesis, we also examine the role these cellular processes play in regulating tissue regeneration and repair.  In particular, we are interested in how stem cells interact with the surrounding niche.  We utilize epidermal development and skin as a model tissue to study stem cell regulation.  Two stem cell compartments have been described in the skin, the interfollicular stem cell niche and the bulge stem cell niche adjacent to the hair follicle.  The architecture of both of these niches differs considerably, and one key question is whether similar extracellular signals from the niche are transmitted in similar or different manners to the independent epidermal stem cell compartments.  We are currently investigating how stem cell:cell adhesion and polarity proteins regulate the signals originating from the niche.



Developing mouse skin forms diverse types of cell:cell contacts. Cells comprising the skin of wild-type animals organize the actin cytoskeleton (green) at sites of cell:cell contacts. This regulation directs the proper positioning of the basal progenitor layer above the basement membrane of the skin (red). Normal skin (left) has a very ordered basal layer but loss of Merlin (right) results in disorganization of the basal cell layer and actin at cell:cell contacts.