Study the pathological features of diseases using induced pluripotent stem cells derived form patient's somatic cells
The limited experimental access to disease-affected human tissues has severely impeded the elucidating of molecular mechanisms underlying disease development. Generation of induced pluripotent stem cells (iPSCs) by over-expression of defined transcription factors in somatic cells, in particular in those from patient somatic cells, presents an attractive and promising approach to model the early stages of diseases in vitro and to screen novel biomarkers as well as therapeutic medicines. Recently, many research groups have independently reported that patient-specific iPSC-derived cells recapitulated multiple features of pathological events of a particular disease, offering experimental evidence of utilizing patient-specific iPSCs to model diseases and reevaluate the current therapies. We have derived iPSC lines using somatic cells of patients suffering from Klinefelter's Syndrome (KS) and Alzheimer's Disease (AD) and explored the possibility to use these iPSC lines to recapitulate the pathological features of the diseases. Our results show that patient's specific iPSC lines provide good opportunity to study the development and treatment of diseases.
Study the pathological features of diseases using induced pluripotent stem cells derived form patient's somatic cells
The limited experimental access to disease-affected human tissues has severely impeded the elucidating of molecular mechanisms underlying disease development. Generation of induced pluripotent stem cells (iPSCs) by over-expression of defined transcription factors in somatic cells, in particular in those from patient somatic cells, presents an attractive and promising approach to model the early stages of diseases in vitro and to screen novel biomarkers as well as therapeutic medicines. Recently, many research groups have independently reported that patient-specific iPSC-derived cells recapitulated multiple features of pathological events of a particular disease, offering experimental evidence of utilizing patient-specific iPSCs to model diseases and reevaluate the current therapies. We have derived iPSC lines using somatic cells of patients suffering from Klinefelter's Syndrome (KS) and Alzheimer's Disease (AD) and explored the possibility to use these iPSC lines to recapitulate the pathological features of the diseases. Our results show that patient's specific iPSC lines provide good opportunity to study the development and treatment of diseases.
Novel signaling by the IKK complex
Signal transduction plays a pivot role in regulating cell functions, from proliferation, differentiation, programmed cell death, and transformation. Deregulation of signal transduction could lead to various human diseases even cancer. Extracellular signals are transmitted into cells via an intracellular signaling network that is composed of multiple signaling pathways, dictating cellular functions, such as growth, differentiation, programmed death (apoptosis) and transformation.
Although we have learnt a great deal about the architecture of the intracellular signaling network, our understanding of its biology is limited. The work in my laboratory focuses on elucidating molecular mechanisms underlying plasticity and specificity of intracellular signaling network using c- Jun N-terminal protein kinase (JNK) and IkB kinase (IKK)/NF-kappaB as molecular probes and understanding the impact of deregulating the intracellular signaling network on human diseases
Telomeres and Aging
端粒是染色体末端的特殊结构，它由简单重复的DNA 序列和与之结合的蛋白质构成，保护染色体末端不被降解或融合，并使染色体能够完全复制。端粒长度的维持以及端粒结构的稳定在细胞衰老、癌症发生以及干细胞全能性自我更新能力维持等生命过程中都起重要作用。
Genomics in the “Century of Biology”
完整基因组测序已为包括肺癌在内的若干种癌症类型的突变谱提供了线索。最新测序技术意味着，现在有可能从全基因组范围内来观察突变差异，而且现在研究人员对肺癌已经做到了这一点
Erich Gnaiger：Life Style and Mitochondrial Competence – Modern Drugs for T2 Diabetes in Aging and Degenerative Diseases.
D. Swarovski Research Laboratory (Mitochondrial Physiology), Dept. General, Visceral and Transplant Surgery, Innsbruck Medical University; and OROBOROS INSTRUMENTS, Innsbruck, Austria. - Email: erich.gnaiger@oroboros.at
The contribution of mitochondrial dysfunction to the etiology of T2 diabetes and a range of preventable metabolic diseases is the subject of intensive current research with world-wide health implications.
Recently these investigations gained depth and scope by technological advances for diagnosis of mitochondrial function by comprehensive OXPHOS analysis using high-resolution respirometry [1,2]. Fundamental questions of a causal relationship, however, between compromised mitochondrial function and development of T2 diabetes remain to be resolved [3,4] to optimize prevention and treatment of insulin resistance.
For preventable diseases such as T2 diabetes, the evolutionary background of mitochondrial competence provides a solid basis for improved and broad application of a well established modern drug, mtLSD.
Post-industrial societies are characterized by a high-energy input lifestyle with diminished physical activity and high incidence of non-transmittable diseases, in comparison to human populations where physical work is essentially important for sustaining life and in which degenerative diseases (T2 diabetes, various cancers, Alzheimer's) are essentially absent [5]. The capacity of oxidative phosphorylation (OXPHOS) is increased or maintained high by a life style involving endurance exercise and strength training [6].
Life style changes from the age of 20-30 years to the elderly, but is subject to change and intervention. Depending on group selection in cross-sectional studies, OXPHOS capacity declines from the age of 20-30 years [7,8], or is independent of age up to 80 years [9,10].
Independent of age, there is a strong decline of OXPHOS capacity in human vastus lateralis from BMI of 20 to 30 [1]. At a BMI >30, a threshold OXPHOS capacity is reached in human v. lateralis that may be characteristic of a low-grade inflammatory state (‘mitochondrial fever’).
Onset of degenerative diseases (T2 diabetes, neuromuscular degeneration, various cancers) and mitochondrial dysfunction interact in an amplification loop progressing slowly with age, such that cause and effect of mitochondrial dysfunction cannot be distinguished. Diminished antioxidant capacity at low mitochondrial density is an important mechanistic candidate in the state of mitochondrial fever.
For implementing a life style supporting mitochondrial competence and preventing degenerative diseases in modern societies, we need (1) extended research programmes focused on the causative link between mitochondrial competence and effective prevention of degenerative diseases, (2) educational programmes on mitochondrial physiology targeted at general practitioners, teachers and the society at large, (3) cooperation of health care and insurance organizations to support preventive life style activities, and (4) do not miss any opportunity in taking the lead in living the mtLife Style Drug (mtLSD).
Fluidigm Biomark-陈巍学基因（22）
Fluidigm公司出品的Biomark系统，是一个基于微流控的，高通量的实时定量PCR系统。它可以高效、快速地对多个样本的、多个基因的表达量进行检测，也可以对多个样本的、多个SNP位点进行分型。同时它还可以大量地节约试剂、人工、实验时间。
本视频介绍了Biomark系统的工作原理，和其优势、特点。
秦正红：DRAM1 regulates autophagy flux and Bid-mediated cell death via lysosomes
秦正红，博士，教授，神经药理专业博士生导师。1994年在美国宾州医学院研究生院获博士学位，先后在美国国家卫生研究院(NIH)及麻省总医院和哈佛大学医学院从事研究工作。2003年从哈佛大学引进，现为苏州大学医学部基础医学与生物科学学院科研中心实验室主任，中国药理学会生化药理学专业委员会委员，中国药理学会神经药理学专业委员会委员，美国神经科学学会会员。
Damage-regulated autophagy modulator1 (DRAM1), a novel TP53 target gene, is an evolutionarily conserved lysosomal protein and plays an essential role in TP53-dependent autophagy activation and apoptosis (Crighton et al, 2006). However, the mechanisms by which DRAM1 promotes autophagy and apoptosis are not clear.
3-Nitropropionic acid (3-NP) is an inhibitor of mitochondrial respiratory complex II. Intrastriatal administration of 3-NP produces neuropathology resemble to Huntington disease. 3-NP-induced neuronal death was involved in autophagy and apoptosis. In vitro studies with 3-NP in TP53 wt and null cells, 3-NP or CCCP increased the protein levels of DRAM1 in a TP53-dependent or independent manner. DRAM1 induction contributed to 3-NP-induced autophagy activation. Knock-down of DRAM1 with siRNA inhibited the activity of V-ATPase, acidification of lysosomes and activation of lysosomal proteases. Knock-down of DRAM1 reduced the clearance of autophagososmes.
3-NP also induced a transcription independent upregulation of BAX protein levels. Knock-down of DRAM1 suppressed the increase in BAX levels. Co-immunoprecipitation and pull-down studies revealed an interaction of DRAM1 and BAX protein. Stably expression of exogenous DRAM1 increased the half-life of BAX. Upregulation of DRAM1 recruited BAX to lysosomes and induced cathepsin B-dependent cleavage of Bid and cytochrome c release. Knockdown of DRAM1, BAX or inhibition of lysosomal enzymes reduced 3-NP-induced cytochrome c release and cell death.
These data suggest that DRAM1 plays important roles in regulating autophagy flux and apoptosis. DRAM1 promotes autophagy flux through a mechanism involves activation of V-ATPase and enhances the acidification of lysosomes. DRAM1 promotes apoptosis via a mechanism involving recruitment of BAX to lysosomes to trigger cathepsin B-mediated Bid cleavage.