Projects
1, Project of LEI Qunying’s Laboratory(雷群英，医学院分子细胞生物学实验室）：Acetylation Control of Cancer Metabolism
Cancer metabolism has re-emerged as an international hot topic in recent years. Our laboratory and other groups’ studies found more than 2,000 cytoplasmic proteins are potentially regulated by acetylation including almost every metabolism enzyme. Our further studies have found acetylation regulation plays essential role in cancer metabolism, and recently we demonstrated PKM2 acetylation at K305 promotes its lysosome degradation via chaperon-mediated autophagy to accelerate cancer metabolism and tumor growth, while acetylation at K5 negatively regulates LDHA and is decreased in human pancreatic cancer. We will focus on the important metabolism enzymes to define their regulation and function in Warburg effect.
2, Project of LIANG Chunmin’s Laboratory(梁春敏,医学院细胞与肿瘤免疫学实验室)：A study on the correlation between the expression of chemokine receptor CCR7 and induced EMT in gastric carcinoma microenvironment
Our project aims to illustrate the correlation between the expression of chemokine receptor CCR7 and induced EMT in gastric carcinoma microenvironment. In vitro, culturing gastric carcinoma cells become the basic technique. Then we induce the cells to experience EMT by adding the cytokines TGF-beta1 and TNF-alpha and try to verify how the CCR7 expression changes as the epithelia cells has a mesenchymal phenotype, which will be achieved with the benefit of the techniques: ICC, Western Blot, Elisa and Flow Cytometry. In vivo, we put our focus on the clinical specimen by the help of IHC to find out the relationship between CCR7 and the overall survival.
3，Project of CHENG Yunfeng’s Laboratory(程韵枫, 中山医院实验研究中心)：Th cell and their cytokines in ITP patients
Immune thrombocytopenia (ITP), also known as idiopathic thrombocytopenic purpura or immune thrombocytopenic purpura, is an immune-mediated acquired disease of adults and children characterized by transient or persistent decrease of the platelet count and, depending upon the degree of thrombocytopenia, increased risk of bleeding. People who have ITP may have nosebleeds, bleeding from the gums during dental work, or other bleeding that's hard to stop. Women who have ITP may have menstrual bleeding that's heavier than normal.
ITP is traditionally considered an auto-antibody mediated disease. Recently the role of T cell immunity in ITP has been recognized and discussed by various researchers. In order to investigate changes in Th (T helper) cell subgrouping and their cytokines of ITP patients, we will enroll ITP patients to measuere the expression of Th cells and their cytokines using real-time PCR and flow cytometry.
4，Project of SHI Dongyun’s Laboratory(施冬云, 医学院生化系):
1)The role of redox microenvironment in regulating tumor specific energy metabolism
It is known that one of the common features of many solid tumors is a hypoxic growth microenviroment in vivo. Normally, hypoxia will induce a decrease of mitochondrial oxygen consumption and ATP generation. In order to maintain rapid growth, tumor cells usually have elevated aerobic glycolysis (the Warburg effect) to meet their energy requirements. It is necessary for tumor cells to apply a kind of energy compensatory strategy in a hypoxic microenviroment. Therefore tumor cells should have the specific energy metabolism mechanisms and biological features that should be different from normal cells. Our study is based these points: that tumor cells show the Warburg effect, that tumor cell growth relies on ROS, and that tumor cells usually have higher level of oxidative stress compared to normal cells. Our results have shown that regulation of the redox microenvironment can effectively modulate the abnormally upregulated glycolytic pathway. This could be a promising target in early diagnosis and treatment for tumor. We expect to find targets to selectively kill tumor cells and exploit a new strategy to inhibit cancer through interference with energy pathways.
2) The effect of fat and oxidative stress microenvironment in type II diabetes
Oxidative stress, through the production of reactive oxygen species (ROS), has been proposed as the root cause underlying the development type 2 diabetes mellitus (T2DM). It has also been implicated in the progression of long-term diabetes complications, including diabetic nephropathy, microvascular and macrovascular dysfunction. Our project will use cell and animal model to explore the mechanism of oxidative stress in development of T2DM. We will focus on the role of fat and oxidative stress in alteration of the metabolic pathway in diabetes and its prevention and the relative mechanisms.
5, Project of HE Rui’s Laboratory(何睿, 医学院免疫学系): Regulatory mechanism of immune inflammation
The main research interests in my lab include 1) the understanding of the molecular mechanism of T helper cells (Th) differentiation and their roles in the pathogenesis of immune-related inflammatory diseases, such as allergic diseases and autoimmune diseases, 2) the understanding of the contribution of tissue inflammation to cancer development.
Ongoing projects
1)The role of LTB4-BLT1 axis in the acute and chronic tissue inflammation.
2)The cellular and molecular mechanism of autoimmune skin diseases, such as cutaneous lupus and psoriasis.
3)The innate and adaptive mechanism of asthma
The immune mechanism by which stromal cells regulate tumor development
6, Project of Yang Pengyuan’s Laboratory(杨芃原,生物医学研究院蛋白质中心):Genome-wide Proteomic study on Hepatitis-Hepatocellular Carcinomar Cells.
The major research interests of Dr. Pengyuan Yang Lab are:
1) Developing new technology and methodology for the identification of protein and protein post-translational-modification (like glycosylation)
2) Profiling healthy and disease human liver proteome and transcriptome, looking for disease related biomarkers and mechanisms systematically
3) Genome-wide proteomic identification (deep-sequencing) and quantitation based on MRM/SRM technology.
7, Project of LIU Yinkun’s Laboratory(刘银坤, 生物医学研究院癌症研究中心,)：Glycan Changes of GP73 in Hepatocellular carcinoma (HCC) Cell Lines
Protein glycosylation plays an important role in many biological processes and the alteration of protein glycosylation have been observed in many diseases. For example, the core fucosylated AFP could be detected by a lectin, LCA. This form was referred to AFP-L3 which was a biomarker for the diagnosis of AFP negative HCC. Recently, fucosylated Golgi protein-73 (GP73) was reported to be a major specific marker for early HCC. We investigated the glycan patterns of GP73 in various HCC cell lines (L02, HepG2, Huh7, SMMC7721, MHCC97L, MHCC97H, and HCCLM3). Eight tumor related lectins (WGA, PHA-E, AAL, LCA, PHA-L, Con A, SNA, and DSA) were selected to analyze GP73 glycoforms. Blotting index analysis suggested that fucosylation and bisecting GlcNAc of GP73 glycan were increased along with the metastatic potential of the four cell lines (Huh7, MHCC97L, MHCC97H, and HCCLM3) by LCA and PHA-E lectin blot. Further, we will confirm the glycan variations in different cell lines via LC-MS/MS, which will give a detail of the glycan information of proteins. Western blot was also used to measure GP73 protein. The protein expression level of GP73 was found to be higher in the metastatic cell lines than that in the non-metastatic cell lines. In addition, the function of GP73 is also studied in this work. And the relationship between glycan of GP73 and its function will be elucidated.
8, Project of QIN Lunxiu’s Laboratory(钦伦秀, 中山医院肝外科):The Molecular Mechanisms of Osteopontin involved in Epithelial-mesenchymal Transition and Metastasis in Hepatocellular Carcinoma
Our previous studies have demonstrated that osteopontin (OPN) is a promoter for hepatocellular carcinoma (HCC) metastasis. Epithelial-mesenchymal transition (EMT) in cancer cells plays a pivotal role in determining metastatic process. In this study, we aimed to explore the functional roles of OPN in regulating EMT of HCC. OPN and EMT marker, expression in HCC were measured by quantitative reverse transcriptase PCR (qRT-PCR), Western blot and immunohistochemistry analyses. The biological consequences of EMT regulated by up- and down-regulation of OPN in HCC cell lines were studied both in vitro and in vivo.
9, Project of ZHANG Jiayi’s Laboratory(张嘉漪, 脑科学研究院)：Wireless control of brain circuit activity
Activities in the brain circuit reflect and control the sensory, motor and emotional behaviors of human being. Optogenetics is a novel technology that enabled us to precisely manipulate the activities, therefore interfere with behaviors. Our laboratory have been using optogenetics to study how our visual system develops, and demonstrated the importance of timing in activities. We aim to develop a simple wireless system to manipulate activities in the visual system based on optogenetics technology. We will also use the system to study whether it is possible to mimic direction-selective function by manipulating direction-selective brain circuit activity in dark.
10, Project of DONG Yi’s Laboratory(董毅,医学神经生物学国家重点实验室): The mechanism of the interaction of multiple neurotransmitters in the neural circuits of depression mice
Most research in the depression field focused on the monoamine theory of depression and the neural circuits in hippocampus and frontal cortex. While recent studies found that glutamatergic system, serotonergic system and the dopamine system were involved in depressive disorders. And there was the increasing realization that the dopamine system in the VTA-NAc reward circuit had a crucial role in depression. However, the interactions of these neurotransmitter systems in neural circuits were still unclear. In this project, we will study the function of 5-HTergic projection from DR and the glutamatergic projection from BLA in the VTA and NAc of social-defeat stress mice by using behavioral, electrophysiological, biochemical and pharmacological methods. The results may provide improtant clues for understanding the interactions of these neurotransmitter systems in neural circuits and provide effective clues for the development of new drugs.
11， Project of LAI Bin’s Laboratory(来宾, 医学神经生物学国家重点实验室):The influence and mechanism of morphine on neuronal dendritic spines in different brain regions of reward neural circuits
Pioids can lead to the reward neural circuits function remodeling, this remodeling including synaptic function remodeling and neuron morphological remodeling. The neuron dendritic spines reduce of reward neural circuits related brain regions caused by chronic morphine application is an important performance of neuronal morphological remodeling. However, existing studies only described this phenomena,its mechanism and role in morphine addiction remains unclear. In this project we will study the impact of morphine application on reward neural circuits neuron dendritic spines from multiple perspectives, such as different brain regions, different projection direction, different types of neurons as well as different types of dendritic spines; To explore the role of neurotransmitter and it's receptor in neuron dendritic spines reduce and it's molecular mechanism; To find effective methods or targets to reverse morphine induced neuron dendritic spines reduce and illuminate the role of reward neural circuits neuron dendritic spines reduce in morphine addiction.