Research Focus
We are interested in understanding the molecular mechanisms and signaling pathways that regulate cell adhesion and cell migration associated with cancer cell invasion and metastasis, development and mechanotransduction
Why Study Cell Adhesion?
The dynamic adhesion of cells to their surrounding extracellular matrix provides many of the environmental cues necessary for controlling cell migration, cell shape, survival, proliferation and differentiation. These fundamental events regulate an organism’s normal development, maintenance, and recovery from injury and infection. Defects in the signaling pathways associated with cell adhesion provide the basis for cell transformation and cancer cell metastasis, various developmental defects and cardiovascular disease.
Approach
We use a multi-faceted approach combining biochemistry, cell and molecular biology and various high-end microscopy techniques, including time-lapse and super resolution techniques to determine the molecular organization of the proteins that are involved in cell adhesion and thereby understand how they each contribute to cell behavior. We are primarily focused on characterizing the function of the molecular scaffold/adapter proteins Paxillin and Hic-5. We have found that these multi-domain proteins bind numerous structural and signaling proteins including kinases, phosphatases and Rho family GTPase regulators and effectors to regulate focal adhesion dynamics and signaling, cytoskeletal remodeling and gene expression.
Mike Brown/Turner lab
Animal and 3D Organoid models
Some of our more recent studies have explored the role of paxillin and Hic-5 in coordinating cell migration and tissue remodeling within three-dimensional matrix models. These systems more-readily mimic the stromal tissue environment found in vivo and have provided unique insight into paxillin family function in matrix deposition/remodeling and tissue morphogenesis, as well as cell migration. Through these and other novel approaches, we have also revealed new and unexpected roles for paxillin/Hic-5 in coordinating mechanosignaling and durotaxis, the cell polarity machinery, microtubule acetylation, vesicle trafficking and the emerging field of intermediate filament/focal adhesion crosstalk.
We have also recently developed new knockout mouse model systems for both paxillin and Hic-5 that will provide my program with the ability to study the function of these proteins in development and disease in vivo and in 3D ex vivo organoid culture
Weiyi Xu/Turner lab
Training
The mentoring and training of the future generation of cell biologists has always been a high priority of mine. I have directly supervised over 25 doctoral students and postdoctoral fellows, with most going on to have successful careers in academia and industry. All students and fellows are encouraged to become rigorous and independent experimentalists, attend national meetings, such as ASCB and GRC conferences to present their work and network within the scientific community. Many have been successful in obtaining individual pre- and postdoctoral fellowships.
