Undergraduate Internships

Internship position available for Biochemistry Internship course (BIOC4966)

Time: Summer semester 2016
Location: The 2nd People’s Hospital of Shenzhen
Address: 深圳笋岗西路3002号

Projects available:

Investigation of the anti-cancer effect and underlying mechanism of epigallocatechin-3-gallate (EGCG) on bladder cancer via PI3K/AKT pathway

Abstract: Epigallocatechin-3-gallate (EGCG), the most abundant and bioactive catechin in green tea, has been demonstrated to have anti- oxidation and other effects; it is the potential natural medicine. Bladder cancer is one of the most malignant cancer types, and studies revealed that activation of PI3K/AKT pathway plays an important role in bladder cancer development. Seldom studies elucidated the efficacy and underlying mechanism of EGCG in bladder cancer. Our previous study showed that EGCG inhibited bladder cancer cell proliferation, migration, and also down regulated phosphorylation-level of PI3K and AKT in bladder cancer. Thus, we hypothesized that EGCG inhibited bladder cancer development through PI3K/AKT pathway. In the following study, pathway inhibitors and over expression of AKT will be included to confirm the important role of PI3K/AKT pathway in EGCG induced apoptosis in bladder cancer; western blot and co-immunoprecipitation would be performed to analysis the underlying mechanism of EGCG on the pathway; and the nude mice tumor model and orthotopic murine bladder cancer model will be used to investigate the anti-tumor, anti-metastasis and immunomodulation effects of EGCG in bladder cancer, and some pathway relevant protein would also be tested in the tumor. In conclusion, this study will provide scientific evidence for the anti-cancer effect and underlying mechanism of EGCG on bladder cancer, and also provide technologic guidance for clinical application and potential supplements of EGCG against bladder cancer.
Synthetic genetic circuits that regulate cell fate decision

Abstract: Synthetic biology is bringing together engineers and biologists to design and build novel biomolecular components, networks and pathways, and to use these constructs to rewire and reprogram organisms. Synthetic biology progresses quickly. It is transforming from designing basic modules to addressing practical applications. Our project is trying to construct genetic circuits that may regulate cancer cell oncogene signaling, to explore the application of synthetic biology in cancer cell fate decision and reprogram. We use MAPK signaling as our target signaling. MAPK signaling is a highly conserved oncogene pathway, which has mutations in more than one third of human cancers. New methods targeting MAPK pathway activity will have huge application potential.
CRISPR/Cas9-based light-inducible genetic circuit for intervening bladder cancer cell

Abstract: Genetic circuit combined with specific targets of cancer cell has opened up a new avenue for cancer precision medicine. However, due to a lack of artificial switch, the current CRISPR/Cas9-based genetic circuit for bladder cancer (BC) is not able to modulate gene expression in precision, thus can not assure therapeutic safety in future. Light as a gene switch with extremely high resolution offers an ideal solution. We have proved that the constitutive CRISPR/Cas9-based light-inducible genetic circuit is able to regulate gene expression and inhibit proliferation of BC efficiently. Therefore, we speculated that it's possible to intervene BC in a specific and modulatable manner, by combination of the BC specific targets and CRISPR/Cas9-based light-inducible gene expression technology. The project will optimize the condition of light-inducible gene expression, design logic And Gate genetic circuit using specific promoters of BC, and investigate the efficiency and molecular mechanism of the genetic circuit for intervening BC by different effector genes. The research will establish a new specific and modulatable genetic circuit, providing theoretical and experimental basis for the development of precision treatment methods for BC.
Transcriptional cofactor Mask2 mediates the function of bladder cancer cell growth and invasion induced by YAP

Abstract: Bladder cancer is a malignant tumor of urinary system with high incidence, so it is necessary to find effective therapeutic targets for it. The highly conserved Hippo signaling pathway is an important pathway involved in tumorigenesis and development, however, the function and mechanism of the novel downstream transcription cofactor Mask2 in bladder is not clear, so it's necessary to carry on further research. In our previous studies, we find that YAP is highly expressed in many clinical samples of bladder cancer patients; Overexpression of YAP in bladder cancer cells is able to promote cell growth and the downstream target genes' expression of Hippo signaling pathways involved in restricting cell growth and migration; Knockdown of transcriptional cofactor Mask2 is able to inhibit cell growth and the downstream target genes' expression of Hippo signaling pathways; In further study, we find knockdown of Mask2 is able to inhibit bladder cancer cell grow induced by the excessive expression of YAP. Therefore, we hypothesize that Mask2 mediates the function of bladder cancer cell growth and invasion induced by YAP. This project plans to clarify the function and mechanism of Mask2 in process of bladder cancer cell growth and migration both in vitro and in vivo, to offer essential scientific basis for new targets of bladder cancer treatment.
Transformation of CART cell specific recognition of bladder cancer stem cells

Abstract: Bladder cancer is one of the most common malignant tumors worldwide and great threat to human health. The recurrence and metastasis of cancer after radiotherapy and chemotherapy is still a serious problem that needs to be faced.This project aims to isolate tumor stem cells from bladder cancer tissue and transform CAR-T cells to make it specific torecognize bladder cancer stem cell surface molecular markers. Utilization of synthetic biological methods, we design and construct optically controlled gene expression of key components in CAR-T cell control switch system, to create a regulation by light activated pre-CAR-T cells, expressing the corresponding antibody to CAR-T cell recognition and better removal of bladder cancer stem cells.

The 2nd People’s Hospital of Shenzhen will provide free accommodation in Shenzhen and meals at the hospital staff canteen (up to ¥800 per month, enough for food at the hospital canteen) for the interns.

Interested students can apply directly to Dr. Weiren Huang 黄卫人博士 via email: [pony8980@163.com].