Ming-Cheng Tsai

 

 

Shiang-Jong Tzeng

Tsai, Ming-Cheng

Assistant Professor

MD., Ph.D., Northwestern University 

Address: Room 18, 11F, College of Medicine, NTU.

TEL: (02)23123456-88314

FAX: (02)23915297

email to prof. Tzeng

專長 成果 研究方向   重點設備
 

 

Specialties

1] Immunopharmacology and Antibody Drugs

2] Molecular Cell Biology

3] Obstetrics and Gynecology

 


 

Research highlights

My research is mainly centered on antibody receptor and its ligand, i.e. antibody. We study their function, interaction, and signal transduction in health and in disease using both in vitro and in vivo approaches. At the receptor arm, we primarily focus on the inhibitory Fc receptor, i.e. FcγRIIB (CD32B). FcγRIIB is the dominant inhibitory receptor on B cells to negatively regulate B-cell antigen receptor (BCR) primarily and also other activating receptors, e.g. BAFF receptor and TLRs. As such mice deficient in FcγRIIB result in expansion of antibody-secreting cells, leading to lupus-like disease and ultimately renal failure and demise.

Most of current therapeutic antibodies are IgG-based. Despite of different affinities they all bind to members of Fcγ receptor family, of which FcγRIIB is the only inhibitory receptor. Since FcγRIIB is well known to play a dominant role in negative regulation on various activating receptors in immune cells, it is anticipated to affect the action of therapeutic antibodies in vivo. This makes it an ideal target for drug development for fine tuning of the immune response. As a proof-of-concept, we have screened compounds to this end and positively validated their efficacy in lupus prone mice. Currently we are extending this theme of pharmacological modulation to other diseases, including tumor, infection, stroke and neurodegenerative disorders. To take a step further, we have generated several lines of transgenic mice defective in inhibitory function of FcγRIIB to investigate its physiological outcome in response to IgG antibody and antigen-antibody immune complexes (antigen-specific (cognate) versus antigen non-specific (non-cognate)) in health, e.g. vaccination, and in disease, e.g. autoimmunity. One unique caveat of FcγRIIB is that it plays an essential role in the tight control of both quantity and quality of antibody production in humans. To further explore the importance of this, we have taken on the generation of human broadly neutralizing antibodies against influenza as a main focus at the antibody arm. My other interests include immune tolerance, reproductive immunology and stem cell immunology, e.g. thymus and neural tissue.  Development of pharmacological agent (chemical and protein)- as well as cell (immune and stem cell)-based immunotherapeutics for patients is the long goal.

近期代表著作:

1] Live cell imaging reveals that the inhibitory FcγRIIB destabilizes B-cell receptor membrane-lipid interactions and blocks immune synapse formation. J. Immunol, 180:793-9. 2008.  [Abstract]

2] The B cell inhibitory Fc receptor triggers apoptosis by a novel c-Abl family kinase-dependent pathway. J. Biol. Chem. 280:35247-54. 2005.  [Abstract]

3] Isolation of lipid rafts from B lymphocytes. Methods Mol. Biol. 271:213-24. 2004.  [Abstract]

4] Location is everything: lipid rafts and immune cell signaling. Annu. Rev. Immunol. 21:457-81. 2003.  [Abstract] 

 


Projects

1] Inhibitory Fc receptor and other inhibitory immune receptors

2] Mechanism and application of inhibitory receptors in autoimmunity, tumor immunity, neuroinflammation and vaccination

3] Antibody gene cloning and antibody engineering, e.g. anti-influenza antibody

4] Development of antibody-based as well as cell-based immunotherapeutics

 

 


Facilities

1] Nucleofector II

2] MACSmix homogenizer

 

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