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SELECTBIO Conferences Extracellular Vesicles 2023: Drug Delivery, Biologics & Therapeutics

Michal Toborek's Biography

Michal Toborek, Professor and Vice-Chair for Research, University of Miami School of Medicine

Michal Toborek is a Leonard M. Miller Professor of Biochemistry and Molecular Biology and Vice-Chair for Research in the Department of Biochemistry and Molecular Biology at the University of Miami. Prior to getting a PhD (1989) in Biochemistry from the Silesian School of Medicine in Katowice, Poland, he obtained an MD degree in 1985 from the same institution. After completion of his PhD degree, he moved to the University of Kentucky for his post-doctoral work and gradually rose to the ranks. In 2011, we moved to the University of Miami Miller School of Medicine. The main research interest in his laboratory is focused on the involvement of the blood-brain barrier (BBB) in the pathomechanisms of cerebrovascular and neurodegenerative disorders. He extensively published on the role of the BBB in HIV trafficking into the brain. Other projects in his laboratory have also been focused to study the interactions between drugs of abuse, exercise, and BBB integrity. His research is supported by several NIH grants. Dr. Toborek is a founding member of the International Brain Barriers Society and a member of the Scientific Council for the International Symposia on Signaling at the Blood-Brain Barriers. Dr. Toborek served on numerous NIH study section and is the past President of the Society on Neuroimmune Pharmacology (SNIP). In 2014, he received the Wybran Award from SNIP, the highest honor bestowed by SNIP in recognition of the very best scientific contributions that have resulted in the preservation and expansion of the field of Neuroimmune Pharmacology. His most recent recognitions include Doctor honoris causa titles from the Academy of Physical Education, Katowice, Poland and from the Silesian School of Medicine, Honorary Membership in the Romanian Academy of Medical Sciences, and the Distinguished Services Award from SNIP. He was also recognized as an Expertscape World Expert in the Blood-Brain Barrier.

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Extracellular Vesicle-Mediated Amyloid Transfer and Intercellular Communication within the Neurovascular Unit

Thursday, 27 July 2023 at 16:45

Add to Calendar ▼2023-07-27 16:45:002023-07-27 17:45:00Europe/LondonExtracellular Vesicle-Mediated Amyloid Transfer and Intercellular Communication within the Neurovascular UnitExtracellular Vesicles 2023: Drug Delivery, Biologics and Therapeutics in Orlando, FloridaOrlando,

It is widely accepted that elevated brain deposits of amyloid beta (A-beta) contribute to neuropathology in Alzheimer’s disease. Additionally, A-beta deposition was demonstrated to be elevated in the brains of HIV-infected patients and associated with neuro-cognitive decline; however, the mechanisms of these processes are poorly understood. The role of the blood-brain barrier (BBB) as an interface for the transfer of A-beta from the periphery into the brain and the cells of neurovascular unit is poorly characterized. Indeed, substantial population of neural progenitor cells (NPC) reside near brain capillaries that form the BBB. The purpose of this study is to understand the impact of brain endothelium-derived extracellular vesicles containing A-beta (A-beta-EVs) on metabolic functions and differentiation of NPCs. Mechanistically, we focused on the role of mitochondria, the receptor for advanced glycation end products (RAGE), and activation of the inflammasome on these events. We demonstrate that physiological concentrations of A-beta-40 can transfer and accumulate in NPCs via endothelial EVs. This transfer results in mitochondrial dysfunction, disrupting cristae morphology, metabolic rates, fusion and fission dynamics of NPCs, as well as their neurite development. Moreover, our results show that A-beta partly co-localized with the inflammasome markers ASC and NLRP3 in the recipient NPCs. This co-localization was affected by HIV and RAGE inhibition by a high-affinity specific inhibitor, FPS-ZM1. Interestingly, both A-beta-EVs and RAGE inhibition altered NPC differentiation. Overall, our data indicates that intercellular transfer of A-beta-40 is carried out by brain endothelium derived EVs that can induce mitochondrial dysfunction and alter cellular signaling, leading to aberrant neurogenesis of NPCs. These events may modulate EV-mediated amyloid pathology in the HIV-infected brain and contribute to the development of HIV-associated neuro-cognitive disorders.

Add to Calendar ▼2023-07-26 00:00:002023-07-27 00:00:00Europe/LondonExtracellular Vesicles 2023: Drug Delivery, Biologics and TherapeuticsExtracellular Vesicles 2023: Drug Delivery, Biologics and Therapeutics in Orlando, FloridaOrlando,