Research Highlights Come Learn about our School's Research
Doing chemistry on proteins to unravel complex redox biology and develop new drug modalities – Dr. Clive Chung
While it seems unusual to put “chemistry” and “protein” together in a sentence, in every second there are thousands of chemical reactions occurring on proteins in living systems. Certainly these are not explosive chemical reactions as you will see when you put a piece of sodium metal in acid. Instead, living systems are very smart and can initiate, regulate or terminate chemical reactions on proteins in highly controllable manners. An example is phosphorylation on protein, a post-translational modification where a phosphoryl group is attached to nucleophilic amino acids such as serine, threonine or tyrosine. Phosphorylation can significantly change the protein functions and activities, thus resulting in signaling cascades to control other chemical reactions to regulate important biological processes such as growth and development.
Unlike protein phosphorylation which can be detected readily by western blotting, another type of chemistry on proteins: oxidation and reduction, i.e. redox biology, is much less
explored. This is not because this redox biology is not important in living systems as it has long been hypothesized for its close associations with disease development and progression such as cancers and neurodegenerative disorders. Yet, studying redox chemistry on proteins is very challenging because this chemistry (oxidation or reduction) is highly dynamic and unstable, and cannot be detected by most of the conventional experiments. Dr. Clive Chung’s lab is trying to tackle this problem by turning the unstable redox chemistry on protein into a permanent modification using their specific chemical probes. With this permanent modification, his lab can then identify proteins involved in redox biology by confocal fluorescence microscopy, gel-based experiments and advance LC-MS/MS. Some of these proteins are found to be important targets for cancer development, thus uncovering the missing link between redox biology and cancers down to molecular level.
Dr. Clive Chung's webpage
Dr. Clive Chung’s lab is also developing new chemistry on proteins for expanding the pool of proteins that can be bound and drugged, aiming at developing new drug modalities for more effective cancer therapy and overcome drug resistance found in current cancer therapy by drugging new protein targets. To know more, please come to L1-05 and have a chat with Dr. Clive Chung’s team!
The highly conserved respiratory system of air breathing animals represents a major interface between internal organs and the environment. In the course of a typical human lifespan, approximately 200 to 400 million liters of air are conducted via the respiratory system. While the pulmonary function has been adapted for organismal physiology and aging, it is also vulnerable to diseases including COVID-19, asthma, COPD, fibrosis, and cancer. Morphogenesis of the respiratory system takes place during embryogenesis and generates diverse cell types with distinct physiological functions. After birth, when mammals are transitioned from the amniotic fluid to air breathing, the airway forms a protective mucosal barrier, clears inhaled pathogens, and generates innate and adaptive immune responses to harmful signals. Surprisingly, how this vital barrier forms and functions at the molecular level, and how dysfunction leads to diseases, are poorly characterized. Building the airway using human organoids: from form to function - Dr. Mu He
In the He lab at the SBMS at Faculty of Medicine, we are leveraging the power of stem cell biology, live imaging, human organoids, and single-cell technologies to understand how the respiratory system develops, repairs, and regenerates. Our lab focuses on the respiratory epithelial cells as the entry point to address fundamental questions pertaining to human airway development and physiology, including: 1) how is the airway mucosal barrier differentiated before the first breath, 2) how do airways balance mucus secretion and clearance, and 3) how do mucosal commensal microbiome and pathogen shape airway regeneration and function? Given the species-specific differences in airway biology between mice and humans, new approaches are needed, and we are using new model systems and performing comparative studies to reveal unifying principles of regeneration. Through proactive collaboration between research and medicine, our ultimate goal is to translate basic biomedical discovery into effective therapies for patients affected by respiratory diseases.
Dr. Mu He's webpage
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