Our laboratory has developed many of the genetically engineered mouse strains that are being used around the world to overexpress genes in a temporally and spatially controlled manner in the mammary gland and other organs using the tetracycline system and to delete genes in a tissue-specific and temporally controlled fashion using the Cre/loxP and Flp/FRT recombination systems. A list of these published strains can be found on the Resource Page. Several of these models in combination with new and unpublished genetically engineered mouse lines are being used for these ongoing projects in our laboratory:
Role of Janus kinases (JAKs) and Signal Transducers and Activators of Transcription (STATs) in mammary gland and pancreas development as well as cancer initiation and progression
Since its discovery as "just another kinase" more than twenty years ago, the family of JAK tyrosine kinases and their respective Signal Transducers and Activators of Transcription (STATs) have been a center of attention in the areas of signal transduction, development, and cancer. The subsequent designation of JAKs as Janus kinases after the mythical two-faced Roman God of the doorways accurately portrays the analogous and sometimes contrasting molecular and biological characteristics of these tyrosine kinases. The multifaceted nature of JAKs becomes evident from their ability to activate specific STATs during distinct phases of normal mammary gland and pancreas development. Studies in cancer cell lines and genetically engineered mouse models also show that JAK/STAT signaling possesses a "two-faced" role during cancer initiation and progression.
Current investigations by our team focus on newly discovered compensatory functions of JAKs and STATs in the early development of glandular tissues, inflammatory conditions, and cancer progression.
Cellular plasticity in normal and neoplastic mammary epithelial cells
As a response to physiological and pathological conditions, epithelial cells can undergo reprogramming and adopt different fates during normal development and tissue homeostasis as well as mammary tumor progression. In a recent study published in the journal Nature Communications, our team demonstrated how cellular plasticity is orchestrated by oncogenic signals that promote the transition of luminal epithelial cells into basal cells. Subsequently, transforming cells acquire mesenchymal features leading to the genesis of tumors that cluster to the triple-negative mammary cancer subtype, which is referred to as ‘claudin-low’.
For more background information on cellular plasticity please refer to our latest review "Cellular plasticity in mammary gland development and breast cancer" Cancers 15 (23): 5605 (2023).
In ongoing experiments, we use several genetically engineered mouse models and genome-wide sequencing to gain insight into the dynamic processes that promote cellular plasticity during mammary gland development and tumorigenesis in vivo.
As part of this project, we also continue to investigate the role of the TSG101 protein in mammary gland metaplasia.