In Korea, research areas of medical schools have been divided based on organs, diseases, or education curricula. Likewise, medical sciences at Seoul National University (SNU) College of Medicine (SNUCM) are separately conducted by 34 basic and clinical ‘classes’ which represent educational units for medical students. As our understanding on biology and biomedical sciences is explosively deepened and widened, it is becoming clear that a large number of diseases have the same roots in fundamental biological processes, necessitating convergence medical sciences.
In the Convergence Degradation Medicine Center (CDMC), we aim to develop therapeutic strategies by understanding a common root in all diseases. – ‘homeostasis’ at the levels of molecules (proteins and RNAs), their complexes, and subcellular organelles. In principle, cellular homeostasis is regulated by biogenesis, activity alteration, and degradation. Whereas biological research traditionally has focused on ‘biogenesis’ (e.g., transcription) and ‘activity alteration’ (e.g., phosphorylation), relatively little is known about ‘degradation’ medicine. The research of CDMC focuses on protein/RNA complexes and subcellular organelles and the development of “degradation-based” therapeutic tools to treat associated diseases, including incurable rare diseases.
Overview
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Aim 1
- To investigate the functions and mechanisms of degradation of (1) proteins and RNAs, (2) complexes composed on proteins and/or RNAs, and (3) subcellular organelles such as the ER, peroxisomes, Golgi body, lipid droplets, endosomes, lysosomes, and nucleus.
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Aim 2
- To characterize the functional relationship of these degradative processes with human diseases such as cancer, multiple sclerosis, neurodegeneration, alpha-trypsin deficiency syndrome, cystic fibrosis, obesity, diabetes, and NASH.
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Aim 3
- To development therapeutic means through “targeted degradation” of proteins, their complexes, or subcellular organelles, such as AUTOTAC (autophagy-targeting chimera).
The turnover of cellular materials are mediated by the ubiquitin (Ub)-proteasome system (UPS) and the autophagy-lysosome system (hereafter autophagy). The substrates of degradative systems include proteins and RNAs as well as their complexes (e.g., proteasomes, ribosomes, P-bodies, stress granules) and subcellular organelles (the nucleus, mitochondrion, endoplasmic reticulum (ER), peroxisome, and lysosome).
These mechanisms involve pathophysiology and drug targets for various diseases, such as peroxisome biogenesis disorder/Zellweger syndrome, alpha1-antitrypsin deficiency/cystic fibrosis, obesity, non-alcoholic fatty hepatitis (NASH), diabetes, antibiotic-resistant bacteria, and tuberculosis. Many of such diseases represent rare intractable diseases, requiring novel concepts of treatment. The DCMC aims to identify new pathways and mechanisms underlying degradation of intracellular complexes and organelles, to link them to related diseases, and to develop therapeutic strategies. By integrating the results from each subgroup, we aim to establish a new concept of "macroscopic (convergence) degradation medicine" at the levels of the cell and, eventually, the human body
The CDMC is composed of 28 experts in DBMS. Group 1 will focus on the functions and mechanisms underlying degradation of proteins and RNA as well as their complexes such as proteasomes, ribosomes, Cajal bodies, and nuclear pore complexes, P-bodies, and stress granules. Group 2 will focus on subcellular organelles such as the ER, peroxisome, lipid droplet, Golgi body, endosome, and nucleus. Group 3 will investigate the functional relationship of these degradative processes with various diseases. To gain additional expertise, core research groups will participate in various types of collaboration in genetics, proteomics, structural biology, medicinal chemistry, and preclinical trials
