Projects
Name
Peptide antagonists targeting drug resistance associated proteins
University
China (IFMSA-China) - Peking Union Medical College, Beijing
Domain
Biotechnologies and Informatics
Departement
Biomedical Engineering
Head
Haiyan Xu
Tutor
Haiyan Xu
Languages
English
Duration
4 weeks
Availability
Cities/Months Jan Feb Mar Apr May Jun Jul Augt Sep Oct Nov Dec
No No No No No No Yes No No No No No
Type of Research Project
- Basic science
What is the background of the project?
Tumor microenvironment plays a critical role in tumor development and progression. In particular, stroma derived factor 1α (SDF-1α, or termed as CXCL12), and its cognate receptor, the chemokine receptor 4 (CXCR4) and the receptor tyrosine kinase Axl and its ligand Gas6 are two very key receptor-ligand pairs in the cross-talking between tumor cells and their microenvironment. Blocking the interaction between CXCR4 and CXCL12 axis and develop Axl antagonist is an effective approach to inhibit tumor progression and reverse drug resistance.
What is the aim of the project?
CXCR4 antagonist peptide E5 is screened by our laboratory and has shown therapeutic effect on AML mouse model. One aim of this research is to develop DSPE encapsulated E5 (M-E5) to increase the stability and bioactivity of E5. Then apply M-E5 to two primary AML1-ETO mouse models to accomplish pharmacodynamics and pharmacokinetics to complete preclinical study of E5.Meanwhile, screen peptide with high affinity of Axl and encapsulated peptide and chemotherapeutic drugs Dox with DSPE to formulate micelle and explore its effect on AML.
What techniques and methods are used?
1) Detected CXCR4 or Axl or other protein maker expression on cells by C6 Flow Cytometer system. 2) The morphology of the peptide on cells are observed with Confocal microscope by immunostaining. 3) Establishment ETO mouse model. 4) Isolated peripheral blood (PB), spleen and bone cells from mice 5) Detected micelle cytotoxicity by Cell Counting Kit-8 (CCK-8)
What is the role of the student?
- The tasks will be done under supervision
What are the tasks expected to be accomplished by the student?
1) Detected CXCR4 or Axl or other protein maker expression on cells by C6 Flow Cytometer system. 2) The morphology of the peptide on cells are observed with Confocal microscope by immunostaining. 3) Establishment ETO mouse model. 4) Isolated peripheral blood (PB), spleen and bone cells from mice 5) Detected micelle cytotoxicity by Cell Counting Kit-8 (CCK-8)
Will there be any theoretical teaching provided (preliminary readings, lectures, courses, seminars etc)
Preliminary readings will be provided. In addition, the tutor will discuss and explain in detail about the project that students will be conducting. Students are encouraged to take part in the group meeting and seminars.
What is expected from the student at the end of the research exchange? What will be the general outcome of the student?
- The student will prepare a presentation
- The student will prepare a scientific report
- The student’s name will be mentioned in a future publication
What skills are required of the student? Is there any special knowledge or a certain level of studies needed?
The student needs to be familiar with cell culture, flow cytometry, and data analysis.
Are there any legal limitations in the student’s involvement
No
Hours
8
Type of students accepted
This project accepts:
- Medical students
- Students in biomedical fields
Articles
- Li X; et al. A designed peptide targeting CXCR4 displays anti-acute myelocytic leukemia activity in vitro and in vivo. Sci Rep. 2014 Oct 14;4:6610.
- Li X; et al. Improving chemotherapeutic efficiency in acute myeloid leukemia treatments by chemically synthesized peptide interfering with CXCR4/CXCL12 axis. Sci Rep. 2015 Nov 5;5:16228.
- Zhou GB; et al. Oridonin; a diterpenoid extracted from medicinal herbs; targets AML1-ETO fusion protein and shows potent antitumor activity with low adverse effects on t(8;21) leukemia in vitro and in vivo. Blood. 2007 Apr 15;109(8):3441-50.
- Ben-Batalla I; et al.Axl; a prognostic and therapeutic target in acute myeloid leukemia mediates paracrine crosstalk of leukemia cells with bone marrow stroma. Blood. 2013 Oct 3;122(14):2443-52.