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博士后学术沙龙(第92期)
文:李申美 来源:医学院 时间:2024-04-15 846

为搭建我校博士后之间的学术交流平台,促进学术水平提升,学校博士后管理办公室组织开展博士后学术沙龙活动。本次沙龙由我校博士后刘红梅、蒋灵晰、刘文静、侯艳培和王信分享其研究成果,诚挚邀请感兴趣的师生参加。

一、时   间:2024年4月23日(周二)14:30

二、地   点:沙河校区医学院213会议室

三、主办单位:电子科技大学博士后管理办公室

四、承办单位:医学院

                          四川省人民医院

                     电子科技大学博士后联谊会

五、活动安排:

报告一:   

(1)主题:基于工程化细胞膜仿生药物递送系统的胰腺癌免疫治疗研究

(2)主讲人:刘红梅  医学院博士后

(3)交流内容:

胰腺癌是被称为“癌中之王”的难治性肿瘤,免疫检查点阻断(ICB)疗法在多种难治性肿瘤中已经取得良好疗效,但其单独治疗难以在胰腺癌患者中获益,这与其复杂的基质屏障及固有的免疫抑制微环境密切相关,不仅限制了治疗剂的有效递送,还极大降低了胰腺癌对现有药物/免疫治疗的反应率。因此,通过破坏胰腺癌基质屏障、逆转免疫抑制微环境而重塑肿瘤微环境是突破胰腺癌治疗难度大的关键。Defactinib是一种强效的黏着斑激酶抑制剂,可抑制肿瘤微环境中细胞外基质形成,破坏肿瘤基质屏障,促进肿瘤部位药物累积及免疫细胞浸润;藤黄酸是一种多靶点广谱抗癌化合物,除肿瘤细胞毒性作用外,还能诱导免疫原性细胞死亡,激活抗肿瘤免疫;二者与ICB联合应用有望突破胰腺癌基质屏障并强化化疗与免疫协同效应。在这项工作中构建一种癌细胞-红细胞杂化膜仿生的三药共载的介孔二氧化硅纳米递药系统,用于 Defactinib、藤黄酸、免疫检查点阻断剂共递送,探索其通过化疗与免疫治疗协同抗胰腺癌的作用效果,并阐明其对胰腺癌基质以及免疫微环境调控的作用机制,为胰腺癌提供一种新的治疗策略。

(4)主讲人简介:

刘红梅,医学博士,毕业于成都中医药大学西南特色中药资源国家重点实验室,现为电子科技大学与四川省人民医院联合培养博士后,合作导师为蔡璐璐研究员,主要从事肿瘤靶向及微环境响应的纳米药物递送系统的研制及其在癌症的化疗、免疫方面的相关研究工作。目前主持国家自然科学基金青年项目1项、中国博士后科学基金面上项目1项、四川省科技厅重点研发项目1项以及四川省医学会青年创新项目1项。其研究成果在Signal Transduction and Targeted Therapy,Biomaterials,Journal of Controlled Release,International journal of nanomedicine,Small等SCI杂志上发表论文10余篇。

报告二: 

(1)主题:高度近视及其并发症的致病基因挖掘与机制探索

(2)主讲人:蒋灵晰  医学院博士后

(3)交流内容:

我国是近视大国,超过5亿的近视患者和高达1亿的高度近视人群(HM)。近视防控关乎国家和民族的未来,已被提升为国家战略任务,并纳入了政府重要考核指标。遗传是HM的重要原因,为了有效推进近视及其并发症的防治工作,急需阐明HM发病的遗传因素,明确眼球形变发生的触发因素与核心机制。本报告汇报人围绕HM及其并发症的疾病基因和作用机制进行了长期研究,并以发现的核心致病机制为抓手探索出近视新防控药物递送平台。因此,此次汇报将从致病基因挖掘、机制探索和疾病防治3个方向,结合已发表的文章,介绍高度近视及其并发症的相关研究成果。

(4)主讲人简介:

蒋灵晰,电子科大医学院博士后。近五年在国际主流学术期刊以第一/通讯作者(含并列)发表SCI论文14篇(单篇SCI他引最高次数为396次);主持国家和省部级科研项目4项;获国家发明专利授权6项;担任包括Clinical and Translational Medicine在内等多个学术期刊的审稿人。研究方向:致盲性眼科疾病的致病基因与机制探索。

报告三:

(1)主题:Defective CAPSL function causes impaired retinal angiogenesis through the MYC axis and is associated with familial exudative vitreoretinopathy

(2)主讲人: 刘文静  医学院博士后

(3)交流内容:

Familial exudative vitreoretinopathy (FEVR) is a severe genetic disorder characterized by incomplete vascularization of the peripheral retina and associated symptoms that can lead to vision loss. However, the underlying genetic causes of approximately 50% of FEVR cases remain unknown. Here, we report two heterozygous variants, c.88C>T (p.Arg30Ter) and c.247C>T (p.Leu83Phe), in calcyphosine like (CAPSL), from four patients among two unrelated FEVR-affected families. Both variants exhibited compromised CAPSL protein expression. Vascular endothelial cell-specific inactivation of Capsl in postnatal mice resulted in defective sprouting, delayed radial/vertical vascular progression, compromised endothelial proliferation, and impaired cell migration, recapitulating the human FEVR phenotypes. CAPSL-depleted human retina microvascular endothelial cells (HRECs) exhibited impaired tube formation, decreased cell proliferation, disrupted cell polarity establishment and filopodia/lamellipodia formation, as well as disrupted collective cell migration in vitro. Transcriptomic and proteomic profiling of CAPSL-depleted HRECs revealed that CAPSL abolition inhibited the MYC signaling axis, in which the core MYC gene was decreased at the protein level. Furthermore, a combined analysis of CAPSL-depleted HRECs and MYC-depleted human umbilical vein endothelial cells (HUVECs) uncovered similar transcription patterns, highlighting that a compromised MYC signaling axis could potentially contribute to FEVR. Collectively, this study identifies CAPSL as a novel candidate gene for FEVR, delineating a crucial regulatory role of CAPSL in angiogenesis and pinpointing a potential therapeutic target for FEVR.

(4)主讲人简介:

Wenjing Liu received the Doctor's degree from the University of Electronic Science and Technology of China in 2022. She currently works as a Postdoctoral Fellow in the School of Medicine of UESTC and major in exploring the pathogenic genes and mechanisms in retinal eye diseases under the guidance of Professor Xianjun Zhu.

报告四:

(1)主题:TMEM30A参与足细胞损伤的机制研究

(2)主讲人:侯艳培  医学院博士后 

(3)交流内容:

足细胞损伤是多种肾小球疾病如局灶节段性肾小球硬化,微小病变肾病及糖尿病肾病发生发展的关键环节。深入研究足细胞损伤的确切机制,寻找潜在有效的治疗靶点对延缓肾小球疾病以及制定合理的干预策略具有重要意义。本报告的主要内容是将包括以下两个方面:(1)利用足细胞特异性Tmem30a敲除小鼠和Tmem30a敲减的小鼠足细胞,及体内外阿霉素诱导的足细胞损伤模型,明确TMEM30A和焦亡在足细胞损伤中的重要作用,深入探讨TMEM30A/NLRP3炎性小体通路介导的足细胞焦亡致足细胞损伤的机制,为防治FSGS提供新靶点;(2)通过转录组测序数据发现糖酵解通路与足细胞损伤之间的关系,进一步给予Tmem30a过表达质粒进行干预,明确TMEM30A是否可以增加糖酵解相关酶,改善足细胞损伤。

(4)主讲人简介:

侯艳培,医学博士,2022年博士毕业于哈尔滨医科大学,目前作为四川省人民医院和电子科技大学联合培养博士后,主要研究工作包括足细胞病致病机制的相关研究和法布雷病的基因治疗等。

报告五:

(1)主题:Study of the anti-inflammatory and neuroprotective effects of Nurr1 agonists in Parkinson's disease

(2)主讲人:王信  医学院博士后

(3)交流内容:

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the absence of dopaminergic neurons (mDA). Studies have shown that the development of PD is closely related to neuroinflammation and nuclear receptor-associated transcription factor 1 (NURR1) is closely related to mDA genesis and maintenance of its function, as well as is effective in attenuating neuroinflammation in glial cells, therefore the development of Nurr1-related agonists may be a potential treatment for PD.

We found the compounds stimulate astrocytes, microglia, and neurons, respectively. Then, the Effect of different compounds on the promoter activity of Nurr1 downstream genes was detected by protein fluorescent reporter enzymes. We found compounds inhibit the inflammatory response of glial cells in the PD cell model and have a protective effect on neurons. Moreover, A model for specific knockdown of astrocytic Nav1.6 in substantia nigra was successfully constructed in vivo and in vitro to verify whether the anti-inflammatory and neuroprotective effects of the compound are achieved by Nurr1. We will future Culture peripheral single nucleus cells from Nurr1 gene-deficient patients as well as normal people to detect effects on Nurr1 expression.

This study illustrates the compound increases Nurr1 expression and decreases neuroinflammatory as well as increases neuronal TH expression in a PD cell model.

(4)主讲人简介:

Wang Xin received a master's degree from Wuhan University and a Ph.D. degree from the Dalian Medical University in 2019 and 2022, respectively. She currently works as a Postdoctoral Fellow in the medical college of UESTC. Dr. Wang is working in the field of neurodegenerative disease. Her main research interests include the role of key genes on glial cells in the pathogenesis of Parkinson's disease and Alzheimer's disease, as well as Screening of anti-inflammatory and neuroprotective compounds.

   

                                                               电子科技大学博士后管理办公室

                                                                           2024年4月15日


编辑:李果  / 审核:李果  / 发布:陈伟

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