TIGP Molecular Medicine Program

2025 TIGP-MM admission
TIGP molecular medicine program is now accepting applications for the 2025 Fall semester.
The application deadline is Feb. 1st, 2025.
Online application: https://tigp.apps.sinica.edu.tw/index.php
Application requirements: https://www.ibms.sinica.edu.tw/mmp/page/3-1.html
TIGP-MM official website: https://www.ibms.sinica.edu.tw/mmp/index.html #

2024 TIGP-MM admission
TIGP molecular medicine program is now accepting applications for the 2024 Fall semester.
The application deadline is Feb. 1st, 2024.
Online application: https://tigp.apps.sinica.edu.tw/index.php
Application requirements: https://www.ibms.sinica.edu.tw/mmp/page/3-1.html
TIGP-MM official website: https://www.ibms.sinica.edu.tw/mmp/index.html #

📌[Research] 2018/05/03📌

🔎Activation Switch for Cancer Metastasis Discovered, Introducing the Novel PSPC1 Oncogene

　Scientists have uncovered a key oncogene that controls the proliferation and metastasis of cancer cells! In their latest study, research fellow Dr. Yuh-Shan Jou, postdoctoral researcher Dr. Hsi-Wen Yeh, and their research team at the Institute of Biomedical Sciences of Academia Sinica, have found that the paraspeckle component (PSPC1) gene, which is overexpressed in the final stages of cancer causes cancerous cells to proliferate, metastasize, and invade normal tissues. Dr. Yuh-Shan Jou commented that this discovery of PSPC1 is a key regulatory gene for controlling the deterioration and spread of cancer is uncovered by the scientific community. In the future, if scientists can figure out how to inhibit the PSPC1 oncogene, then it will be possible to reduce the growth and spread of cancer cells and contribute to the development of new and more effective cancer drugs.

　Tumor metastasis and the invasion of cancer cells are the main causes of death in cancer patients. However, the mechanisms of metastatic reprogramming in tumor progression remained elusive to scientists. Previous studies have shown that the activation of the transforming growth factor beta 1 (TGF-β1), a secreted protein that performs various cellular functions, is a key mechanism of cancer metastasis. In general, TGF-β1 controls cell growth, cell proliferation, cell differentiation, and apoptosis, activating cytostasis to sustain homeostasis in normal cells. However, this protein exerts dichotomous roles. In contrast to normal cells, in cancerous cells, TGF-β1, in its altered gene expression, acts in the opposite manner, promoting the proliferation, invasion, and metastasis of cancer cells. During the late and advanced stages of cancer, TGF-β1 can be found in large amounts in tumor tissues. Yet, exactly how this “two-faced” protein functions has puzzled scientists since the specific function of TGF-β1 varies depending on the progression of cancer.

　To identify the key factor for cancer metastasis and the specific role that TGF-β1 plays, Dr. Yuh-Shan Jou and his team used integrated cancer genomic approaches to study and analyze tissue samples of malignant tumors from lung cancer, breast cancer, liver cancer, and prostate cancer to look for gene mutations, abnormalities, and other factors related to the survival rate of patients.

　In their analysis of tumors, they identified PSPC1 as a master modulator for the metastatic switch. They also found that PSPC1 is upregulated or overtly expressed in tumor tissues and also responsible for reprogramming the TGF-β1 protein in cancer cells. In other words, in normal cells, PSPC1 is expressed in low levels, and TGF-β1 functions normally, inhibiting cell proliferation; however, when expressed in high levels in cancer cells, PSPC1 interacts with the Smad2/3 protein, which are main signal transducers for receptors of the TGF-β1 protein, to increase TGF-β1 expression and the autocrine signaling of cancer cells. More importantly, PSPC1 preferentially switches Smads targets from cytostatic genes in normal cells to pro-metastatic ones in malignant cancer cells, ultimately creating a favorable environment for the growth and proliferation of cancer cells.

　Poor prognosis and low survival rates in cancer patients are also highly correlated with the over-expression of PSPC1. Besides promoting the proliferation and metastasis of cancer cells, PSPC1 also increases epithelial-mesenchymal transition (EMT) and the growth of cancer stem cells (CSC). As such, if the over-expression of PSPC1 can be suppressed, both cancer cell growth and proliferation can subsequently be reduced.

　Dr. Yuh-Shan Jou noted that both the discovery of the lead role that the PSPC1 oncogene plays in reprograming the mechanism of cell proliferation as well as the corresponding changes found in the function of the TGF-β1 protein are novel and cutting-edge breakthroughs in the field of cancer research. These results offer scientists new food for thought regarding cancer cell proliferation and also shows PSPC1 as a new theranostic target for drugs that can counter cancer metastasis, spurring progress in anticancer drug research.

　This study was published online in Nature Cell Biology on March 28, 2018 and highlighted as a featured article in the News & Views section of the April 2018 issue.

　The full research article entitled “PSPC1 mediates TGF-β1 autocrine signaling and Smad2/3 target switching to promote EMT, stemness and metastasis” is available online through the Nature Cell Biology website at: https://www.nature.com/articles/s41556-018-0062-y. Associated content from a related article, “Paraspeckle factor turns TGF-β1 pro-metastatic,” is also available on the Nature Cell Biology website at: https://www.nature.com/articles/s41556-018-0078-3.

　The lead author of “PSPC1 mediates TGF-β1 autocrine signaling and Smad2/3 target switching to promote EMT, stemness and metastasis” is Dr. Hsi-Wen Yeh. Co-authors include Dr. Yuh-Shan Jou and his research team, Dr. Ruey-Bing Yang (Research Fellow, Institute of Biomedical Sciences, Academia Sinica), Dr. Ching-Feng Cheng (Joint Appointment Associate Research Fellow, Institute of Biomedical Sciences, Academia Sinica and Tzu Chi University), Dr. Ruey-Hwa Chen (Distinguished Research Fellow, Institute of Biological Chemistry, Academia Sinica), Dr. Chian-Feng Chen (Associate Research Fellow, Genome Center, National Yang Ming University), and Dr. Chiung-Tong Chen (Director, Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes).

http://www.ibms.sinica.edu.tw/pi_webpage/blue_style2016/page/highlight_detail.php?p_id=49&pub_id=477

PSPC1 mediates TGF-β1 autocrine signalling and Smad2/3 target switching to promote EMT, stemness and metastasis Yeh et al. find that PSPC1 is upregulated in cancer and interacts with Smad2/3 to induce TGF-β1. This leads to increased autocrine TGF-β1 signalling and a switch to pro-metastatic TGF-β1-dependent gene expression.

🎊🎉Congratulations to Christina Li-Ping Thio (TIGP-MM 2014 enrolled) for her hard work.

Awards & News Detail Short chain fatty acids (SCFAs) are the fermentation products of multiple bacterial phyla, including Bacteroidetes, Firmicutes and Fusobacteria, and exist naturally in our body. The immunoregulatory roles of SCFAs have been extensively studied in intestinal disorders such as inflammatory bowel disea...

📌[Research] 2018/01/25

New insight on therapeutic treatment for mental disorders: A novel regulation of DNA repair mechanism in neurons

Mental disorders affect millions of people around the world and also account for an increasingly significant proportion of medical expenses. A research team led by Dr. Yijuang Chern, a Distinguished Research Fellow in the Institute of Biomedical Sciences at Academia Sinica, recently found a new mechanism underlying DNA repair in neurons. Their findings contribute to the current understanding of diseases with defects in DNA repair (such as mental diseases and neurodegenerative diseases). This study was published on January 3, 2018 in Molecular Psychiatry.
Generally speaking, the human body automatically metabolizes extraneous free radicals and repairs DNA sequences that are damaged by free radicals to ensure that cells function properly. Recent studies have discovered that neurons in patients suffering from mental illnesses show excessive presence of free radicals and the inability to fully repair damaged DNA.
When damaged DNA sequences cannot be properly repaired, these abnormal sequences will be replicated, resulting in abnormal neurotransmission, compromising neuronal survival, and aggravating the development of psychotic disorders. Therefore, how to restore and fix defective DNA repair mechanisms in neurons is a critical area of focus in research on mental disorders.
In their recent study, Dr. Chern and her team discovered a brand new complex that is related to the DNA repair mechanism in neurons—TDG complex. The TDG complex consists of TRAX (translin-associated protein X), DISC1 (disrupted-in-schizophrenia 1), and GSK3β (glycogen synthase kinase 3 beta). TRAX is an interacting protein of the C-terminus of the A2A adenosine receptor (A2AR), which forms a complex with GSK3β and a risk gene for schizophrenia (DISC1). TRAX and DISC1 are proteins associated with mental disorders and that GSK3β kinase is associated with the ability to regulate DNA repair mechanisms. Dr. Chern’s team discovered that activation of A2AR leads to dissociation of the TRAX/DISC1/GSK3β complex (TDG complex).
This is of great interest because TRAX plays a critical role in detecting DNA damage by directly interacting with ATM to trigger the DNA repair machinery. Dissociation of the TDG complex facilitates the release of TRAX from the TDG complex and allows TRAX to enter the nucleus to facilitate DNA repair and subsequently enhance neuronal survival. Collectively, the TDG complex might serve as a potential therapeutic target for the development of novel treatments for diseases resulting from defects in DNA repair.
Although tremendous efforts have been devoted to the development of therapeutic treatments for mental disorders over the past decades, many important aspects regarding these disorders remained elusive. Findings regarding the TDG complex from this study offers new insight for illnesses resulting from deficiencies in DNA repair mechanisms and is expected to aid the development of new treatments for mental illnesses and neurodegenerative diseases in the future.
Dr. Chern and her team’s research article entitled “GSK3β negatively regulates TRAX, a scaffold protein implicated in mental disorders, for NHEJ-mediated DNA repair in neurons” is available at:

GSK3β negatively regulates TRAX, a scaffold protein implicated in mental disorders, for NHEJ-mediated DNA repair in neurons Article

💡[Research] 2018/01/30
🔬Revealing the Mysterious Role of Myosin-Va in the Initial Step of Cilium Assembly

In a research article published in the January issue of the prestigious scientific journal Nature Cell Biology, Dr. Tang K. Tang (a Distinguished Research Fellow) and his lab members at the Institute of Biomedical Sciences (IBMS), Academia Sinica, uncover for the first time the role of Myosin-Va in the initial step of cilium assembly and reveal the underlying mechanism.

Primary cilia are microtubule-based organelles protruding from the apical cell surface to perform a wide variety of biological functions. Defects in cilium assembly cause a number of genetic disorders known as ciliopathies, which are characterized by loss of vision/hearing, disturbing kidney function, organ left-right displacement, and defects in brain development. Cilium assembly is a highly ordered process, which has been classified into the intracellular and the extracellular pathways, depended on cell types. At the very beginning of ciliogenesis, several small preciliary vesicles (PCVs) first appeared and transported to the distal appendage (DA) of the mother centriole (M-centriole), followed by fusing to form a large primary ciliary vesicle (CV). The axoneme, a microtubule-based cytoskeleton, then grows and elongates within the CV, which later forms the ciliary sheath that surrounds the ciliary shaft. The ciliary shaft eventually becomes the ciliary membrane, while the ciliary sheath docks and fuses with the plasma membrane, allowing to protrude a cilium. Although, the structure and morphology of primary cilia has been well documented, the molecular basis that defines the onset of ciliogenesis remains mysterious.

This Nature Cell biology paper demonstrates that the myosin-Va-mediated transportation of preciliary vesicle to the M-centriole is the earliest event that defines the onset of ciliogenesis. The research team found that Myosin-Va is the earliest marker that first appears on PCV, CV, and ciliary sheath during ciliogenesis. Furthermore, Myosin-Va is required for the trafficking of PCVs to the mother centriole in ciliated cells using both the intracellular and the extracellular pathways, implying that this process is universal. Importantly, this paper uncovers molecular mechanisms of an uncharacterized initial step in cilium assembly. Myosin-Va mediates the transportation of PCVs to the centrosomal region surrounding the centrosome through a dynein- and microtubule-dependent pathway, followed by trafficking of myosin-Va-associated PCVs to the M-centriole via the centrosome-associated branched actin network. This important finding provides a molecular basis for in-depth understanding of cilium assembly and human ciliopathy.

The authors of this paper: Chien-Ting Wu, Hsin-Yi Chen, and Tang K. Tang.

Related Websites:
The full research article is available at
https://www.nature.com/articles/s41556-017-0018-7

This work was supported by Academia Sinica Award and the grant from the Ministry of Science and Technology, Taiwan.

📢📢📢Exultant NEWS for young aspirants who wants to pursue high quality Multi Disciplinary PhD programs in one of the meritorious Research center Acadmia Sinica-Taiwan, under Taiwan International Graduate Program (TIGP).

💻TIGP has opened online application system for the new comers, just fill the application form and avail your opportunity to study in the high quality environment. 👨‍🔬👨‍⚕️👍🔬⚗️🗜️🛡️💉💊📊

📅Deadline for accepting the form is 31st March 2018.
👉Online application: https://tigp.apps.sinica.edu.tw/index.php

Don’t wait for long, until its too late. ت❤️

TIGP onLine

🥇Congrats to the TIGP-MM graduates!

🎉The 12th TIGP graduation ceremony🎉

🐁[News] 2017/10/16🐁

📌Chronic neuropathic pain protect heart from ischemia reperfusion injury

Ischemic heart disease or coronary heart disease is the leading cause of death in the world and the 2nd cause of death in Taiwan. Timely restoration of blood flow is the most effective way to rescue myocardium. However, reperfusion can also damage cardiomyocytes due to calcium overload, free radical production and inflammatory cell infiltration. This phenomenon is called ischemia-reperfusion (IR) injury. A team led by Drs. Chien-Chang Chen and Bai Chuang Shyu at the Institute of Biomedical Sciences (IBMS) in Academia Sinica discovered a novel mechanism of chronic neuropathic pain induces cardioprotection against cardiac IR injury in mice. The research was published in the journal Nature Communications on October 10th, 2017.

Cardiac protection can be induced by ischemic preconditioning (IPC) or postconditioning in the heart. IPC can also be applied in distant tissues or organs to protect heart from IR injury which is called remote IPC. Prodromal angina, presented as a form of chest pain, can limit infarct size and is speculated as an innate cardioprotection. Although preinfarction angina-associated cardioprotection is thought to represent a clinical correlation of IPC, it is possible that angina also induces nociceptive signal pathway to provide cardioprotection. It is unclear whether pre-existing chronic pain will also have a similar cardioprotective effect.

Up to 25% of the population is suffering from chronic pain, especially in elder. Ischemic heart disease is also prevalent in the elderly population. However, it is unclear whether this is a relationship between chronic pain and ischemic heart diseases. The team discovered that chronic neuropathic pain in mice reduced IR injury. They showed that the ERK activity and neuronal activity in the anterior nucleus of the paraventricular thalamus (PVA), is required for the chronic neuropathic pain-induced cardioprotection. In addition, direct activation of PVA neuron using pharmacological or optogenetic tools without peripheral injury also provided cardioprotection. Inhibition of parasympathetic nerve activity abolished chronic neuropathic pain-induced cardioprotection. Overall, the team demonstrates that chronic pain induces cardioprotection via a novel central mechanism involving activation of PVA neurons.

The article entitled “Cardioprotection induced in a mouse model of neuropathic pain via anterior nucleus of paraventricular thalamus” can be found at: https://www.nature.com/articles/s41467-017-00891-z

The complete list of authors is: Yi-Fen Cheng, Ya-Ting Chang, Wei-Hsin Chen, Hsi-Chien Shih, Yen-Hui Chen, Bai-Chuang Shyu and Chien-Chang Chen

http://www.ibms.sinica.edu.tw/templates/default/en/news/news_detail.php?nid=263