Pauklin Group | TGFß signalling in cancer stem cells
Our research covers interests in the fields of cancer research and stem cell biology. We focus on the molecular mechanisms of pancreatic cancer formation, particularly the function of TGFβ/Activin/Nodal-Smad2/3 signalling pathway in the formation and maintenance of cancer stem cells in pancreatic ductal adenocarcinomas.
Pancreatic cancers are among the most lethal malignancies in human. They account for approximately 3% of all new cancer cases and the mortality caused by pancreatic cancer is projected to surpass that of other common cancer types in the next decades due to its late diagnosis and limited response to treatment. Evidence has accumulated on a dedifferentiation process of cellular identity during tumorigenesis, and the acquisition of a stem cell-like state of a subpopulation of cells in cancers called cancer stem cells. These cells are exceptionally important because their developmental plasticity allows them to metastasize and give rise to new tumours in the organism.
The TGFβ/Activin/Nodal-Smad2/3 signalling pathway has a central function in tissue and tumour microenvironments. This pathway plays an important role in early development by regulating the self-renewal of human pluripotent stem cells (hPSCs) and germ layer formation, as well as adult pancreatic tissue homeostasis. In addition to controlling human pluripotent stem cells and developmental processes, TGFβ/Activin/Nodal signalling is involved in the formation of pancreatic ductal adenocarcinomas. Our research group is interested in identifying the molecular machineries and gene circuitries that cooperate with TGFβ/Nodal-Smad2/3 signalling in regulating the stem cell-like characteristics of pancreatic cancer stem cells.
We utilizea broad range of research techniques covering human cellculture systems,genome-wide, proteomic, genetic and biochemical methods. These include human cancer stem cell culture systems and human pluripotent stem cells, genome-wide studies (RNA-seq, ChIP-seq, ATAC-seq), proteomics, in vitro mechanistic studies and in vivo experiments.
Collectively, our research provides insight to the signalling pathways and molecular mechanisms essential for the formation and maintenance of pancreatic cancer stem cells, helping to better understand the tumorigenic process, and to uncover novel ways for diagnosing and treating this lethal cancer.
Tumorigenesis and Cancer Stem Cells
Human Pluripotent Stem Cells
Epigenetics and gene expression