Institute of Biological Chemistry, Academia Sinica

Research

Research Theme 1
Targeting host receptors with postbiotics in colorectal cancer: A microbiota-based precision adjuvant therapy

The standard treatments for colorectal cancer (CRC), mainly surgical resection and chemotherapy, are effective to remove the lesion but cannot adjust the composition of gut microbiota. On the other hand, it is well known that microbiomes located in the gastrointestinal lumen impact the development and progression of CRC. The resilient disease-associated microbiota, which may stay in the gut of CRC patients even after treatment, carries a significant risk for recurrence and distal metastasis of the tumor. The unmet need is to develop a new type of microbiota-based precision adjuvant therapy that enhances the efficacy of standard CRC treatment, thus preventing disease relapse. Postbiotics, which are the effective bioactive molecules derived from microbiomes, may promote or suppress oncogenesis through engagement of host receptors. The postbiotic-receptor interaction and downstream cellular responses are the underlying mechanism, which will be tackled by structural approach and signaling study. The mimicry of postbiotic that acts as either an analog or an antagonist for the corresponding host receptor is the deliverable.

Research Theme 2
Healthy heart for healthy aging by gut microbiota: decoding the role of microbial metabolites in myocardial proteostasis

A hallmark of aging-affected heart is the accumulation of oxidized proteins in post-mitotic cardiomyocytes, leading to dysregulation of myocardial proteostasis. As the consequence, the aged heart is highly susceptible to stress, rendering the individual under a significant risk for developing cardiovascular diseases (CVDs). A key challenge in sustaining a healthy heart while aging is to facilitate degradation of cardiac oxidized proteins. For this, we look for effective gut microbial metabolites that regulate oxidative stress and proteolysis in cardiomyocytes. Our goal is to elucidate the mechanism through which the metabolites communicate with the aging heart for proper control of proteostasis. Upon validation, the selected metabolites and their derivatives are the candidates to promote healthy aging.

Degrees and Positions Held

• 1995 – 1999   Ph.D., Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA
• 1992 – 1994   M.S., Toxicology, National Taiwan University College of Medicine
• 1985 – 1989   B.S., Agricultural Chemistry, National Taiwan University College of Agriculture

• 2014 – present   Research Fellow, Institute of Biological Chemistry, Academia Sinica
• 2017 – 2019   Acting Deputy Director, Institute of Biological Chemistry, Academia Sinica
• 2008 – 2014   Associate Research Fellow, Institute of Biological Chemistry, Academia Sinica
• 2003 – 2008   Assistant Research Fellow, Institute of Biological Chemistry, Academia Sinica
• 1999 – 2003   Post-doctoral Research Fellow, Cold Spring Harbor Laboratory, NY, USA

Selected Publications

Active-site cysteine 215 sulfonation targets protein tyrosine phosphatase PTP1B for Cullin1 E3 ligase-mediated degradation. 
Yang CY, Yang CF, Tang XF, Machado LESF, Singh JP, Peti W, Chen CS, Meng TC* 
Free Radic Biol Med (2023)

The catalytic activity of TCPTP is auto-regulated by its intrinsically disordered tail and activated by Integrin alpha-1. 
Singh JP, Li Y, Chen YY, Hsu SD, Page R, Peti W*, Meng TC* 
Nat Commun (2022)

Crystal Structure of TCPTP Unravels an Allosteric Regulatory Role of Helix α7 in Phosphatase Activity. 
Singh JP, Lin MJ, Hsu SF, Peti W, Lee CC*, Meng TC* 
Biochemistry (2021)

Targeting protein tyrosine phosphatase PTP-PEST (PTPN12) for therapeutic intervention in acute myocardial infarction. 
Yang CF, Chen YY, Singh JP, Hsu SF, Liu YW, Yang CY, Chang CW, Chen SN, Shih RH, Hsu SD, Jou YS, Cheng CF*, Meng TC* 
Cardiovasc Res (2020)

Nitrite Protects Neurons Against Hypoxic Damage Through S-nitrosylation of Caspase-6. 
Chen YJ, Liu YC, Liu YW, Lee YB, Huang HC, Chen YY, Shih YH, Lee YC, Cheng CF, Meng TC* 
Antioxid Redox Signal (2019)

Dual specificity phosphatase DUSP6 promotes endothelial inflammation through inducible expression of ICAM-1. 
Hsu SF, Lee YB, Lee YC, Chung AL, Apaya MK, Shyur LF, Cheng CF*, Ho FM*, Meng TC* 
FEBS J (2018)

S-nitrosylation of endogenous protein tyrosine phosphatases in endothelial insulin signaling. 
Hsu MF, Pan KT, Chang FY, Khoo KH, Urlaub H, Cheng CF, Chang GD*, Haj FG*, and Meng TC* 
Free Rad Biol Med (2016)

Substrate specificity and plasticity of FERM-containing protein tyrosine phosphatases. 
Chen KE, Li MY, Chou CC, Ho MR, Chen GC, Meng TC*, Wang AH* 
Structure (2015)

Reciprocal allosteric regulation of p38γ and PTPN3 involves a PDZ domain-modulated complex formation. 
Chen KE, Lin SY, Wu MJ, Ho MR, Santhanam A, Chou CC, Meng TC*, Wang AH* 
Science Signaling (2014)

Nitrite-Mediated S-Nitrosylation of Caspase-3 Prevents Hypoxia-Induced Endothelial Barrier Dysfunction. 
Lai YC, Pan KT, Chang GF, Hsu CH, Khoo KH, Hung CH, Jiang YJ, Ho FM, Meng TC* 
Circulation Research (2011)

Publication List