Understanding the complexity of molecular and cellular regulation in cancer cells for therapeutic application is my life goal. As cancer biologists, we have been exposed to both basic and clinical research backgrounds. We have also been collaborating with pharmaceutical companies for for studying clinical cancer therapeutics and developed important tools and models to understand medulloblastoma, a severe children brain tumor. Aberrant activated Hedgehog pathway has contributed to more than 20% of medulloblastoma development. To further explore how Hedgehog signalling in medulloblastoma and other cancers, we will combine proteomics, genetics and pharmacological approaches to understand the mechanism in cancer and target the abnormal molecules to eliminate cancer.
Introduction of Hedgehog pathway
Deficiency in the process of embryo development will lead to birth defect and severe disease, such as cancer. The Hedgehog (Hh) pathway is a conserved signaling system essential for embryonic development. I am interested to understand how Hh signaling regulates embryo development by using mouse/ zebrafish model. Upon ligand stimulation, Hh pathway promotes cell proliferation, differentiation and migration. However, how the negative regulators modulate signaling during embryo development still remains unknown. Mutations that deregulate Hh signalling have been implicated in basal cell carcinoma and medulloblastoma and of great translational significance. Using siRNA library screening and proteomics approach, revealing several important hits for Hh regulation. Now, we would like to verify those candidates and figure out how those genes impact on Hh pathway.
Introduction of Hedgehog pathway
Deficiency in the process of embryo development will lead to birth defect and severe disease, such as cancer. The Hedgehog (Hh) pathway is a conserved signaling system essential for embryonic development. I am interested to understand how Hh signaling regulates embryo development by using mouse/ zebrafish model. Upon ligand stimulation, Hh pathway promotes cell proliferation, differentiation and migration. However, how the negative regulators modulate signaling during embryo development still remains unknown. Mutations that deregulate Hh signalling have been implicated in basal cell carcinoma and medulloblastoma and of great translational significance. Using siRNA library screening and proteomics approach, revealing several important hits for Hh regulation. Now, we would like to verify those candidates and figure out how those genes impact on Hh pathway.
Fig. 1 Hh signalling in primary cilia. Under normal regulation, the twelve transmembrane protein, Patch1 will inhibit smoothen (Smo)-seven transmembrane protein. The Gli3 transcriptional repressor turns off Hh downstream genes such as Gli1 and Patch1. When sonic Hh binds to Patch1 will release the inhibitory domain of Smo and accumulates in the primary cilium and through multiple cascades, Gli1, transcriptional activator, will translocate into nuclear and turn on Hh targets.
The master energy sensor, AMPK
AMP-activated protein kinase (AMPK) is a sensor of energy status that maintains cellular energy homeostasis. It arises very early during eukaryotic evolution, and its ancestral role is in the response to starvation. Recent work shows that the kinase is activated by not only increased AMP, but also increased ADP. Although best known for its effects on metabolism, AMPK has many other functions, including regulation of mitochondrial biogenesis and disposal, autophagy, cell polarity, and cell growth and proliferation. Both tumor cells and viruses establish mechanisms to down-regulate AMPK, allowing them to escape its restraining influences on growth.
AMP-activated protein kinase (AMPK) is a sensor of energy status that maintains cellular energy homeostasis. It arises very early during eukaryotic evolution, and its ancestral role is in the response to starvation. Recent work shows that the kinase is activated by not only increased AMP, but also increased ADP. Although best known for its effects on metabolism, AMPK has many other functions, including regulation of mitochondrial biogenesis and disposal, autophagy, cell polarity, and cell growth and proliferation. Both tumor cells and viruses establish mechanisms to down-regulate AMPK, allowing them to escape its restraining influences on growth.