Dr. Andrew B. Gladden
The University of Texas MD Anderson Cancer Center
Department of Genetics
The main focus of our research is to gain insight into the role of cell adhesion pathways in the development and homeostasis of tissues and organs and how disruption of these pathways contributes to tumor initiation and progression to metastasis. Our laboratory utilizes numerous approaches to address this overarching goal, including: genetic mouse models, cell culture studies, organotypic cultures, and biochemistry.
Mammalian epithelial cells organize membrane domains in relation to surrounding cells and extracellular matrix via signals emanating from cell:cell contacts. In particular, the adherens junction (AJ) facilitates intercellular signaling via cell:cell adhesion and helps to define the cell autonomous boundary between the apical and basal regions of the cell. We are investigating how the junctional polarity complex-- which comprises the core AJ proteins E-cadherin and α-catenin, the polarity proteins PAR3 and aPKC, and the NF2 tumor suppressor, Merlin as well as other proteins-- regulates both cell polarity and adhesion in cells and tissue.
The progression from a benign to metastatic cancer generally requires epithelial to mesenchymal transition (EMT), a process in which epithelial cells dissolve cell:cell contacts, lose polarity, and gain mobility. We are interested in how the actin cytoskeleton and cell polarity proteins regulate tumor progression. We hope to enhance our understanding of how solid tumor cells target specific signaling pathways to progress into metastatic lesions, with the goal of developing new biomarkers to monitor benign tumors for specific metastatic signatures.
Finally, we are studying how cell:cell adhesion and communication contribute to the regulation of the adult stem cell niche. To address this question we utilize mouse models as well as isolated stem cells. Future projects will utilize organotypic cultures and epidermal reconstitution methods to expand our knowledge of how cell adhesion and the cell cytoskeleton maintain and activate epidermal stem cells.