National Sun Yat-sen University

Glyco-Biomedicine Lab

Chuang, Po-Kai
https://ibms.nsysu.edu.tw/p/412-1332-23637.php?Lang=zh-tw

Research Field

Medicine

Introduction

Research and development with 14 years of experience in the functional study of globo-series glycosphingolipids and cancers. Adept in handling several research projects that advanced in the interaction of biological mechanisms and glycans. Can accomplish research design, experimental data analytics, investigation, and development in a wide range of therapeutic areas. Looking to leverage well collaboration, research planning, and new technique contribution skill in studying the interplay of glycosphingolipids and antitumor immunity.

I would like to bring the novel knowledge of glycobiology, oncology, and immune therapy back to Taiwan, especially the correlation between cellular biochemistry and glycoscience. In my current research, we found that the tumor cells not only need highly glycosyl metabolism pathways for survival but also express specific glycans for promoting cancer survival signals and escaping immune cell attacks (as known as immunosuppression). 

On the other hand, We are making an effort to enhance antibodies' effectivity and antibody-vaccinal effects by glycosyl-engineering on the Fc domain in the animal study. This modification made that human immune cells quickly recognized to antibodies and increased binding affinity for ADCC(Antibody-dependent cellular cytotoxicity) or ADCP(Antibody-dependent cellular phagocytosis).

In our Lab, you will learn the below devices that would be as a tool for addressing our research and getting the skill to work in the bio-industry.

  1. Flow cytometry: To analyze the cell surface marker and sort out specific cell populations for further cell functional assay or interactions.
  2. LC-MS/MS: Profiling the cell composition and molecular and glycans sequencing.
  3. Laminar flow: For cell culturing and cell assay.
  4. Antibody glycoengineering.
  5. Animal study for tumor therapy.
  6. Colony technique: You will get the skill to edit the gene sequence and build up your own plasmid to transform this plasmid in an expression host (ex: E.coli)
  7. Protein expression and purification: You can transfect target plasmid in the mammalian cells to express target protein and purification pure protein form mixture as well.
  8. Confocal Microscope: To grab images from living cells or fixation cells by Fluorescence labeling.
  9. Immune cell isolation and culturing: To isolate specific immune cells as cell sources for cell therapy, including NK cells and Macrophages.
  10. Glycan array and lectin array: For screening the interacted glycans.
  11. Biacore (Surface. Plasmon resonance, SPR): A label-free kinetic affinity analysis for protein-protein interaction and protein-glycan interaction.
  12. Western blot and qPCR for verification of protein and gene expression.


Research Topics

Glycoengineering Antibody and Antibody-dependent Cell-mediated Cytotoxicity (ADCC) Enhancement and Antibody-mediated Vaccinal Effect. 

In our previous study, Antibody has homologous glycosylation that can increase the affinity to the Fc receptor to enhance ADCC functions in NK cells. This finding is good for improving the antibody-drug design and efficiency. In addition, we found that the antibody treatment with tumors or influenza will generate a memory immune response to protect the host against recurrence and infection. However, the mechanism is not clear so far. Therefore, we are going to establish the animal model to study this antibody-mediated vaccinal effect and to figure out the regulatory mechanism.

Desialylation and Immune Checkpoint Therapy Design.

Dr. Carolyn Bertozzi was awarded the 2022 Nobel Prize in Chemistry. In her recent studies, she found that the sialo-glycans will inhibit the NK cell functions by negative regulatory signaling on the NK cell surface to suppress the ADCC functional activity or other positive regulatory immune attacks. However, there are no defined glycans and receptors involved in these inhibitory reactions. According to this hypothesis, our research group found that Siglec 9 plays an important receptor in interacting with sialo-glycans to suppress NK cell functions. The effect of this interaction is similar to PD1-PDL1 immune suppression. Thus, In this study, we are going to examine several approaches to block immunosuppression, such as antibody development, inhibitor, and desialylation therapy to select the best way for immune therapy.

Anti-SSEA3 Humanized Antibody Development and Antibody-dependent Cellular Phagocytosis (ADCP).

In our current study, we found that the glycoengineering antibody is able to promote the ability of M1 macrophages for phagocytosis. M1 macrophage expressed Fc gamma RI receptor and Fc gamma RIIIA receptor, However Fc gamma RI receptor have obviously stronger binding with antibody than Fc gamma RIIIA receptor. Therefore, We are going to investigate and develop the Fc domain and optimal the glycans that specifically bind to the Fc gamma RI receptor to destroy the tumor mass or tumor stem cells and increase the antibody-mediated vaccinal effect. 


Honor

American Association of Pharmaceutical Scientists (AAPS) member


Educational Background

Assistant Professor, Institute of Biomedical Sciences, National Sun Yat-sen University, 2023-present

Postdoctoral associate, Department of Chemistry, The Scripps Research Institute, La Jolla, California, 2019-2023

Postdoctoral Fellow, Genomics Research Center, Academia Sinica, Taipei, Taiwan, 2018-2019

Ph.D., Institute of Basic Medical Sciences, National Cheng Kung University, 2010-2018


2 Vacancies

Job Description

Cell assay 

Molecular biology assay

Glycobiology

The mechanism of drug resistance

Immune therapy

Preferred Intern Education Level

Bachelor's degree,  Master's degree, or PhD student

Skill sets or Qualities

(Required but not necessary. You can gain these abilities in our Lab)

Cell biofunctional assay

Molecular biologic assay

Antibody and protein engineering, expression, and purification