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Dr. Meng-Chiao  Ho
Assistant Research Fellow
Room 316, Institute of Biological Chemistry, Academia Sinica
128, Academia Road Sec. 2, Nankang, Taipei 115, Taiwan
TEL: +886-2-2785-5696 ext. 3080
FAX: +886-2-2788-9759
Meng-Chiao Ho's Website

Our research interests are mainly focused on the structure, function, and biophysical properties of proteins. The information we discovered can further guide the inhibitor design to aid in cancer therapy or enzyme engineering for industrial uses. We conduct our studies primarily using X-ray crystallography, spectroscopy and enzymology and routinely collaborates with other laboratories worldwide. Your can find more about us at http://ho.ibc.sinica.edu.tw/

Our current studies involves three areas: (a) reconstruct the rice survival strategy under submergence (b) protein-protein interaction related to cancer (c) enzyme engineering for industrial use.

Reconstruct the rice survival strategy under submergence:
• Most rice cultivars die within a week of complete submergence, but some rice cultivars show high tolerance and survive up to two weeks under complete submergence. It’s believed that Sub1A is the key transcription factor that regulates quiescence responses enabling prolonged submergence. We aim to understand Sub1A1 regulatory networks. We will study the DNA binding specificity of Sub1A-1 to reveal the downstream signaling pathway via biochemical and biophysical approaches combined with our microarray data and the functions of other domains by structural approaches.

Protein-protein interaction related to cancer:
• The receptor-like protein tyrosine phosphatase-α (rPTPα) is a crucial player in mediating RTK/Src signal transduction pathways. Because rPTPα can activate Src and is overexpressed in various cancers, rPTPα is considered as proto-oncogene. The rPTPα can be phosphorylated by RTK to become the active form, and is also subject to oxidation by ROS. However, detailed information at the molecular level is missing largely due to lack of structures of true protein-phosphoprotein complexes. The major challenges in such structural studies include 1) to produce a large quantity of protein-phosphoprotein complexes involving specifically modified rPTPα; 2) to crystallize the protein complexes. We would like to address a) how rPTPα activates the activity of Src b) how oxidation of rPTPα affects its activity to activate Src.
• Protein arginine methyltransferases (PRMTs) play roles in cancer progression by methylating many cancer related proteins. However, the question remains which protein methylation leads to oncogenic activation. Our structural approaches focusing on PRMT-protein complex provide a way to answer this question and can assist inhibitor design to prevent methylation for cancer therapy.
• KLHL20, a protein adaptor, interacts with the tumor suppressor, PML. This interaction induces the degradation of PML which leads to tumor progression. Inhibitors that prevent KLHL20-PML interaction may be useful in cancer therapy. We are now working on the KLHL20-PML complex structure which can provide a blueprint for inhibitor design.

Enzyme engineering for industrial use:
• Many enzymes that catalyze specific reactions have industrial applications. The biochemical/biophysical modifications of enzymes by protein engineering can broaden the uses in the industry. Based on structural analyses, we aim to improve chemical properties of cellulase (substrate variety) for biofuel application and physical properties (heat and pH tolerance) of our patented keratinase for animal feed application.

2001.09 - 2007.11 Ph.D., Physiology & Biophysics, Boston University
1995 - 1999 B.S., Chemistry, National Tsing-Hua University

2011,08 - present Assistant Research Fellow, Institute of Biological Chemistry, Academia Sinica
2007,12 - 2011,07 postdoctoral researcher, Albert Einstein College of Medicine of Yeshiva University

    Publications List
Diamidine compounds for selective inhibition of protein arginine methyltransferase 1.
Yan L, Yan C, Qian K, Su H, Kofsky-Wofford SA, Lee WC, Zhao X, Ho MC, Ivanov I, Zheng YG Journal of medicinal chemistry (2014)
Catalytic Site Conformations in Human PNP by (19)F-NMR and Crystallography.
Suarez J, Haapalainen AM, Cahill SM, Ho MC, Yan F, Almo SC, Schramm VL Chemistry & biology (2013)
Structure of the Arginine Methyltransferase PRMT5-MEP50 Reveals a Mechanism for Substrate Specificity.
Meng-Chiao Ho, Carola Wilczek, Jeffrey B. Bonanno, Li Xing, Janina Seznec, Tsutomu Matsui, Lester G. Carter, Takashi Onikubo, P. Rajesh Kumar, Man K. Chan, Michael Brenowitz, R. Holland Cheng, Ulf Reimer, Steven C. Almo, David Shechter PLoS ONE (2013)
Characterizing DNA methyltransferases with an ultrasensitive luciferase-linked continuous assay.
Hemeon I, Gutierrez J.A., Ho MC., Schramm V.L. Anal Chem. (2011)
Entropy-driven binding of picomolar transition state analogue inhibitors to human 5'-methylthioadenosine phosphorylase.
Guan R, Ho MC, Brenowitz M, Tyler PC, Evans GB, Almo SC, Schramm VL Biochemistry (2011)
Methylthioinosine phosphorylase from Pseudomonas aeruginosa. Structure and annotation of a novel enzyme in quorum sensing.
Guan R, Ho MC, Almo SC, Schramm VL Biochemistry (2011)
Four generations of transition-state analogues for human purine nucleoside phosphorylase.
Ho MC, Shi W, Rinaldo-Matthis A, Tyler PC, Evans GB, Clinch K, Almo SC, Schramm VL Proceedings of the National Academy of Sciences of the United States of America (2010)
A phosphoenzyme mimic, overlapping catalytic sites and reaction coordinate motion for human NAMPT.
Burgos ES, Ho MC, Almo SC, Schramm VL Proceedings of the National Academy of Sciences of the United States of America (2009)
The origin of the electrostatic perturbation in acetoacetate decarboxylase.
Ho MC, Menetret JF, Tsuruta H, Allen KN Nature (2009)
Transition state analogues in structures of ricin and saporin ribosome-inactivating proteins.
Ho MC, Sturm MB, Almo SC, Schramm VL Proceedings of the National Academy of Sciences of the United States of America (2009)

Updated 2017.03.08

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