Completed: May 30 Webinar Neurodevelopment & NeurodegenerationNRR Series Webinar: Title: Neurodevelopment & Neurodegeneration Date and Time: The 30th of May, Tuesday 20:30-21:40 (Beijing) | 14:30-15:40 (CET) | 7:30 am-8:40 am (CST) | 8:30 am-9:40 am (EST)
PROGRAM
Speaker 1:
Professor of Neuroscience & Cell Biology, Rutgers University-Robert Wood Johnson Medical School, USA Speech Title: New roles of integrin-K+ channel complexes as mediators of neurodevelopment and its associated developmental channelopathies
About the speaker: The laboratory of Prof. Federico Sesti studies the physiology, regulation and biophysics of potassium (K+) channels. K+ channels are integral membrane proteins whose primary function in the nervous system, is to modulate the wide variety of firing patterns that are required for processing information and generating motor outputs. In addition, K+ channels can also control cellular functions in ways that do not directly depend on their conducting properties. Channels engage receptors and other signaling molecules to perform non-ionic roles, especially integrins, which play multi-faceted roles in cell signaling. Their studies show that stimulation of integrin-KCNB1 complexes leads to the engagement of Focal Adhesion kinase (FAK), Src family tyrosine kinases, Ras GTPases and Protein kinase B (Akt) resulting in cytoskeletal remodeling, proliferation and growth. In the presence of significant oxidative stress (the imbalance between reactive oxygen species, ROS, and antioxidants), like in the Alzheimer's brain or following a brain trauma, the ROS cause irreversible structural modifications in KCNB1 channels (cross-linking). These modifications are interpreted by the integrins as detachment from the extracellular matrix, a requirement for survival. Consequently, the signaling pathway diverges at some point downstream Ras inducing the activation of via MAPK family c-Jun N-terminal kinases, which promote oxidative stress and eventually cellular death. Current projects focus on elucidating the role of integrin-KCNB1 signaling in Alzheimer's disease and Traumatic Brain Injury. They are also assessing the potential therapeutic of second generation Bcr-Abl and Src tyrosine kinase inhibitors and BACE1 inhibitors for the treatment of those pathologies.
Yijing Su Research Assistant Professor Department of Neuroscience and Mahoney Institute for Neurosciences, Perelman School of Medicine, University of Pennsylvania, USA Speech title: A Single-Cell Transcriptome Atlas of Glia Diversity in the Human Hippocampus across the Postnatal Lifespan and Alzhimer's Disease About the speaker: Research in their laboratory centers on understanding molecular mechanisms underlying neurodevelopment and how its dysregulation may contribute to developmental neurological disorders. The lab uses a combination of experimental approaches that include molecular biology, biochemistry, mouse genetics, imaging, electrophysiology, electron microscopy, optogenetic manipulations, next generation sequencing, and behavioral tests to study neural development. They have been using two complementary model systems, the genetically modified mouse system and patient-derived induced pluripotent stem cell (iPSC) model systems. They are interested in addressing a broad range of topics, from neuronal migration, axon and dendritic development, synapse formation, circuitry integration to plasticity of developing neurons, and functional regeneration of mature neurons. Dr. Yijing Su’s research focuses on understanding epigenetic changes during neuronal activation and its role in neuronal function in both population and single cell levels.
Session Chair: Yang Li Principle investigator Fudan University, China About the Session Chair: Shanghai Young Outstanding Academic Leader, member of the State Key Laboratory of Medical Neurobiology and the Key Laboratory of Metabolism and Molecular Medicine of the Ministry of Education. Dr. Li’s lab focus on the regulation of lysosome homeostasis and its role in improving Alzheimer's disease. By using small-molecule compounds as probes, novel mechanisms of lysosomal biogenesis have been revealed. On the other hand, LYECs (lysosome-enhancing compounds) will be potential approaches to enhance the degradation efficiency of autolysosomes and ameliorate neurodegenerative diseases. Research papers have been published in Nature, Nature Cell Biology, Alzheimer's & Dementia, Autophagy, JCB, and other high profile journals as the first author or correspondence.
PANELIST 1: Xiang-Yao Li Principle investigator International Institutes of Medicine, the Fourth Affiliated Hospital of Zhejiang University School of Medicine, China About the Panelist: Dr. Li’s primary research interests focus on the neuronal mechanisms of chronic pain. Injuries on the somatosensory pathway would cause neuropathic pain, which affects about 8% of people. His group try to understand the involvements of irregulated synaptic transmission to the developments and maintenance of neuropathic pain.
PANELIST 2: Ling Liu Professor Tongji University School of Medicine, China About the Panelist: Professor of Tongji University, School of Medicine, doctoral supervisor, deputy director of the Department of Pathology and Pathophysiology, member of the 17th People's Congress of Shanghai Putuo District, Council member of Pathophysiology Association of Shanghai, reviewer of NRR, BMC Cancer, Spandidos Publications, JMI, reviewer of graduate dissertations of Ministry of Education, reviewer of National Natural Science Foundation of China. Research interests: Early neurodevelopment of the human brain; Neurodevelopment-related diseases of the human brain; Regeneration and clinical translation of human brain . Academic achievements: Research papers have been published in Cell Research, Cell Death and Differentiation, Plos Pathogens, Stem Cell Reports, Immunology, Cerebral Cortex and other international journals as the first author or correspondence. Grants funded by the National Science and Technology, Science and Technology Commission of Shanghai Municipality, and the national key research and development program of China.
PANELIST 3: Domenico Praticò Scott Richards North Star Foundation Chair Alzheimer's research Director Alzheimer's Center At Temple Professor, Neural Sciences Lewis Katz School of Medicine, Temple University, USA About the Panelist: Dr. Praticò’s research area is clinical pharmacology with a special focus on the cellular and molecular aspects of cell oxidative biology and a particular interest in small molecules such as bioactive oxidized lipids. This area is very broad and extends to multiple disciplines including aging, cardiovascular diseases as well as neurodegeneration. Their work in the biology of oxidized bioactive lipids has significantly contributed to the current understanding of their importance as biomarkers, mediators of cellular and molecular events involved in the pathogenesis of several clinical conditions, and therapeutic targets for preventing and treating human diseases. In our lab we employ cellular and animal models of human diseases, and in this context particular emphasis is given to the translation of any observation made in these systems into a better understanding of human physiology and pathology. Their group is committed to foster collaborative scientific research of the highest quality, and at the same time to provide outstanding teaching and mentoring for young scientists.
PANELIST 4: Xiaoli Shen Full Professor School of Public Health, Qingdao University, China About the Panelist: Her major research interests focus on the etiology and prevention of neurodegenerative disease. Through an ecological study, I found that high concentrations of iron and copper in the soil was associated with the high AD annual mortality in mainland China, providing direct evidence for the involvement of metals in the development of AD. In addition, I found that nesfatin-1, a brain-gut peptides discovered in 2006, could protect dopaminergic neurons against MPP+/MPTP-induced neurotoxicity through the C-Raf-ERK1/2-dependent anti-apoptotic pathway both in vivo and in vitro, suggesting that nesfatin-1 might have therapeutic potential for PD. We also found that reduced nesfatin-1 in the brain may induce nigrostriatal dopaminergic system degeneration; this effect may be mediated via mitochondrial dysfunction-related apoptosis.
PANELIST 5: Xiuquan Wu Attending Physician, Lecturer Xijing Hospital, Fourth Military Medical University, China About the Panelist: Xiuquan Wu, Department of Neurosurgery, Xijing Hospital, the Fourth Military Medical University, Attending physician, Lecturer. Bachelor, master, doctor and postdoctoral candidate, graduated from the Fourth Military Medical University. He studied under Professor Fei Zhou, a famous neurosurgery and traumatologist in China, and his teacher was Professor Yi Shengyu, a pioneer in neurosurgery in China. The research mainly focuses on the molecular pathological mechanism of brain injury and brain injury prevention strategies. Up to now, more than 40 academic papers have been published, 13 SCI papers have been published by the lead author and co lead author, of which the highest impact factor of a single article is 11.061, and 7 patents have been obtained. He have undertaken two excellent degree thesis and doctoral research funding projects, and participated in more than 10 national and provincial level projects, including the National Natural Science Foundation Key Project and 173 Project. Selected for the university's "New Flight Program" talent program, currently serving as a reviewer for SCI journals such as Neural Regeneration Research and Frontiers in Cellular Neuroscience. Main research directions: 1. Carry out a series of basic research on brain injury and make significant progress in the molecular pathological mechanisms of neuronal injury. Focusing on the key molecular mechanisms of neuronal damage repair, research has found that molecules such as Homer, Parkin, and Pink1 can exert neuroprotective effects, and in-depth research has been conducted on their regulatory signaling pathways. Relevant research has been published in high-level journals such as Journal of Neuroinflammation、Cellular and Molecular Life Sciences. 2. Conducting a series of clinical studies on traumatic brain injury has made significant breakthroughs in exacerbating the risk factors of secondary brain injury. Focusing on the key role of risk factors that exacerbate secondary brain injury in the timely prevention and treatment of traumatic brain injury, retrospective and prospective clinical studies were conducted. A database of over 1100 clinical patients was established, and a secondary brain injury risk factor detection system was developed. The study found that multimodal monitoring of secondary brain injury risk factors can benefit the injured. The relevant research was published in the Chinese Journal of Neurotrauma Surgery Journal of Trauma Surgery and other high-level journals, and participated in the writing of guidelines for timely treatment of traumatic brain injury. 3. Conducting a series of applied research on craniocerebral trauma and achieving significant progress in skull regeneration and repair. Focusing on the role of biological 3D printing technology in skull defects caused by war trauma, conducting applied research, and successfully obtaining a new type of skull repair material based on autologous bone powder loaded stem cells. Relevant research has been published in high-level journals such as Biofabrication.
PANELIST 6: Wei Zou Professor Institute of Translational Medicine, Zhejiang University | School of Medicine , China
About the Panelist: Research Interests Molecular mechanisms of dendrite morphogenesis in neurons; Molecular mechanisms of neurodegeneration; Small molecules to suppress neurodegeneration. The main goal of his lab is to understand the molecular mechanisms of neural development and neurodegeneration. We mainly utilize nematode C. elegans as our model organism, which has been proved as a very powerful system to understand the conserved molecular mechanisms of neural development, such as axon guidance and synapse formation. Formation of neural circuit requires precise regulation of both axonal and dendritic guidance. Many axon guidance molecules have been identified and characterized in the last several decades. However, little is known how dendrites are guided during development. During Wei’s postdoctoral training with Dr. David Sherwood at Duke University and Dr. Kang Shen at Stanford University, he has identified several novel dendritic guidance molecules. Among these, LECT-2, the homologue of human LECT2, acts as a co-ligand with two cell adhesion molecules SAX-7/L1CAM and MNR-1/Menorin. These three molecules form a co-ligand complex, which is recognized by the dendritic receptor DMA-1. Activation of DMA-1 requires the presence of each molecule, suggestive of a co-incidence detection mode of recognition to specify the precise location of dendritic arbors. He also found that HPO-30, a claudin-like protein, functions as a co-receptor of DMA-1. HPO-30 and DMA-1 recruit WAVE regulatory complex and TIAM-1/RacGEF, respectively, to promote actin assembly and dendrite formation. To the best of our knowledge, this is the first case to show that a claudin acts as a signaling molecule rather than as a component of tight junctions during neural development.
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