Elucidating the involvement of the Src Kinase substrates, Tks4 and Tks5, in mechanisms of tumor dormancy, progression and metastasis

Ronn is working on several breast cancer cell lines in vitro, using 2D and 3D cell culture techniques to define the role of Tks5 in the formation of invadopodia and in the ECM. He is purifying human Tks5 protein for the generation of monoclonal antibodies. These antibodies will allow us to better determine the localization and roles of Tks5 in cancer cells.
Breast Cancer cells stained with Actin, Tks5 and DAPI. Yellow puncta (merge) indicate invadopodia structures.

Kinases important for functional invadopodia formation in cancer progression. 

Shinji is researching invadopodia-related kinases that have been identified using high content invadopodia screening assay. Currently these candidate kinases are being validated in several cancer types and will be assessed as cancer therapeutic target.

The adaptor protein Tks5 is a critical molecule for invadopodia formation. 

Shinji is also studying the role of invadopodia in cancer progression, especially melanoma and breast cancer, using a mouse model to reveal the role of invadopodia in cancer progression in vivo. 

ventral actin puncta

Understanding the role of Src kinase in cell cycle progression in estrogen receptor-positive breast cancer using an in vitro cell culture system and an in vivo xenograft model

Although canonical estrogen signaling in estrogen receptor-positive (ER+) breast cancer has been the focus of numerous studies, Chris is focusing on the role of Src kinase as a mediator of non-genomic estrogen signaling. Our lab previously showed that Src family kinases (SFKs) are involved in peptide growth factor-mediated cell cycle progression in fibroblasts, and our initial findings suggest the same is true in estrogen-positive breast cancer. We aim to understand the molecular mechanism of estrogen-dependent, Src-mediated cell cycle progression in ER+ breast cancer through in vitro studies as well as test the effects of Src inhibitors in human xenograft mouse models. We hypothesize that these signaling pathways will elucidate novel targets and potential therapeutic targets for ER+ breast cancer patients.
Understanding the role of Src kinase in cell cycle progression in estrogen receptor-positive breast cancer.

The effects of two candidate kinases on invadopodia formation and function

Letitia is investigating the role of two candidate kinases in melanoma and breast cancer cells with regards to invadopodia formation and function. Both of these proteins were highlighted in a previous screen as their knockdown with siRNAs resulted in decreased invadopodia formation and gelatin degradation. She is determining the expression of these kinases and presence of invadopodia in different cell lines to illustrate what effects both over-expression or knockdown would have upon these structures.