医学部系列学术讲座之一

发布者:系统管理员发布时间:2008-05-13浏览次数:230


报告题目:NK Cells in Cancer Immunotherapy

报告人:Dr. Zhou Dapeng

Primary Appointment

Assistant Professor with tenure track, Department of Melanoma Medical Oncology, The University of Texas M. D. Anderson Cancer Center

Joint Appointment

Assistant Professor with tenure track, Department of Immunology, The University of Texas M.D. Anderson Cancer Center, Houston

Member, Graduate School of Biomedical Sciences, University of Texas Health Science Center at Houston.

报告摘要:

NKT cells are a unique subset of T cells that recognize conserved glycolipid antigens, presented by a non-polymorphic, MHC-like antigen presenting molecule CD1d. These T cells are activated in first line of immune defense within two hours after antigen stimulation, and produce cytokines/chemokines that exert critical regulatory effects on adaptive immune system. Specifically, NKT cells instruct the adaptive immune cells how to respond to tumor and pathogens. Chemically synthesized agonist glycolipid ligands for NKT cells trigger their Th1 cytokine release, prevent and cure cancer in mouse models of melanoma and lymphoma. Paradoxically, tumor microenvironment may also induce the NKT cells to produce immune suppressive cytokines. Currently, we are developing two NKT-related projects.

Project 1: Synthetic glycolipid antigens for NKT cells are potential immunomodulators for clinical use. In collaboration with the Immuno-Monitoring Core and the Adoptive Transfer Therapy center of M.D. Anderson, we are studying the biology of NKT cells upon activation with various glycolipid ligands. Our specific aim is to fine tune the NKT cell’s quality of cytokine production and cytotoxicity, as well as their lifespan and efficiency of tumor infiltration. One additional approach provided by our department is to genetically modify T cells by infecting them with a recombinant retrovirus, thereby equipping the T cells with anti-cancer genes that are not normally activated during the T cell’s own differentiation program.

Project 2: Immunosuppression is one of the major mechanisms involved in cancer progression. The immunosuppressive role of NKT cells in cancer patients has been hypothesized to be associated with abnormal expression of tumor-derived glycolipid antigens. We and others have published that a glycosphingolipid, isoglobotrihexosylcermide (iGb3) is a natural ligand for NKT cells. To allow the precise dissection of iGb3 in cancer cells at the molecular and subcellular levels, we have established two tools: 1) mass spectrometry and 2) iGb3-specific monoclonal antibodies. We are using these tools to study the iGb3 expression and function in human cancers including melanoma, leukemia, lymphoma and myeloma.

时间:2008515 1400

地点:附属第一医院影像楼4楼核医学科会议室

欢迎广大师生积极参加。

附:报告人简介:

EDUCATION:

Graduate education:

1994 M.D.,Shanghai First Medical College, Shanghai, China

1997 M.Sc. Biochemistry, Shanghai First Medical College, Shanghai, China

2002 Ph.D. Biochemistry, University of Zurich, Zurich, Switzerland

Postgraduate Training

2002 – 2002 Postdoctoral Fellow – Immunology, Department of Molecular Biology, Princeton University

2002 – 2004 Postdoctoral Fellow – Immunology, Department of Pathology, University of Chicago, Chicago, IL

PUBLICATIONS:

Articles in Peer-Reviewed Journals (selected)

1. Zhou D, Henion T, Jungalwala FB, Berger EG, Hennet T. The {beta} 1, 3-galactosyltransferase beta3GalT-V is a stage-specific embryonic antigen-3 (SSEA-3) synthase. J Biol Chem. 2000 Jul 28; 275(30):22631-4.

2. Bai X*, Zhou D*, Brown J*, Hennet T, Esko JD. Biosynthesis of the linkage region of glycosaminoglycans: Cloning and activity of Galactosyltransferase II, the sixth member of the beta 1, 3 galactosyltransferase gene family (beta3GalT6). J. Biol. Chem. 2001 Dec 21; 276(51):48189-95. (*co-first authors)

3.Henion TR*, Zhou D*, Wolfer DP, Jungalwala FB, Hennet T. Cloning of a mouse beta1,3 N-acetylglucosaminyltransferase Lc3 synthase gene encoding the key regulator of lacto-series glycolipid biosynthesis. J Biol Chem. 2001 Aug 10; 276(32):30261-9. (*co-first authors)

4. Zhou D*, Cantu III C*, Sagiv Y, Schrantz N, Kulkarni AB, QI X, Mahuran DJ, Morales CR, Grabowsky GA, Benlagha, K, Salvage PB, Bendelac AB and Teyton L. Editing of CD1-bound lipid antigens by endosomal lipid transfer proteins. Science. 2004 Jan 23; 303(5657):523-7. (*co-first authors, co-senior authors)

5. Zhou D*, Mattner J, Cantu III C, Yin N, Gao Y, Sagiv Y, Hudspeth K, Wu Y, Teneberg S, Wang D, Proia RL, Levery SB, Teyton L, and Bendelac A*. An endogenous lysosomal glycosphingolipid recognized by mouse and human NKT cells. Science. 2004 Nov 11 online publication. (*correspondence authors)

6. Xia C, Zhou D*, Liu C, Lou Y, Yao Q, Zhang W, Wang PG*.Thio - isoglobotrihexosylceramide, an Agonist for Activating Invariant Natural Killer T Cells. Org Lett. 2006 Nov 23;8(24):5493-5496. (*Co-senior authors)

7. Chen WL, Nadas J, Xia CF, Zhang W, Wang JH, Thapa P, Li YS, Zhou D* and Wang PG. Synthesis and SAR study of isoglobotrihexosylceramide (iGb3) analogs. Submitted. (*Co-Senior authors)

8. Li Y, Zhou D*, Xia C, Wang PG, Levery SB*. Sensitive Quantitation of Isoglobotriaosylceramide in the Presence of Isobaric Components Using Electrospray Ionization-Ion Trap Mass Spectrometry. Glycobiology. 2007 Nov 28; [Epub ahead of print] (*Co-Senior authors)

9. Li Y, Teneberg S, Thapa T, Bendelac A, Levery SB*, Zhou D*. Sensitive detection of Isoglobo and globo series of tetraglycosylceramides in human thymus using Electrospray ionization-Ion Trap Mass Spectrometry. Glycobiology. 2007 Nov 28; [Epub ahead of print] (*Co-Senior authors)

Invited Articles

Zhou D. OX40 signaling directly triggers the anticancer function of NKT cells.

Journal of Clinical Investigation (Commentary). 2007, Nov. 117: 3169-3172.

Zhou D. The immunological function of iGb3. Current Protein and Peptide

Science, 2006, 7(4),325-33

(科研办公室)