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SELECTBIO Conferences Extracellular Vesicle-based Dx & Rx Summit

Extracellular Vesicle-based Dx & Rx Summit Agenda



Co-Located Conference Agendas

Circulating Biomarkers World Congress 2019 | Liquid Biopsies 2019 | Extracellular Vesicle-based Dx & Rx Summit | 

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Thursday, 28 March 2019


Summit Session Title: Emerging Themes in EV-based Diagnostics and Therapeutics


Summit Chairpersons: Professor Lucia Languino and Professor Paul Robbins

11:00

Jan LötvallKeynote Presentation

Diversity of Extracellular Vesicles to Understand their Diagnostic and Therapeutic Potential
Jan Lötvall, Professor, University of Gothenburg; Founding President of ISEV, Sweden

This presentation will discuss the diversity of extracellular vesicles, primarily from a clinical perspective. Specifically, the presentation will show the presence of extracellular vesicles in tissues, specifically healthy tissues as well as different types of tumors.  Data showing the presence of multiple types of EVs in different types of tissues will be presented, as well as the opportunities of utilizing that knowledge for clinical use.

11:30

Lucia LanguinoConference Chair

Exosomes: Novel Opportunities for the Diagnosis and Therapy of Cancer
Lucia Languino, Professor of Cancer Biology, Thomas Jefferson University, United States of America

12:00

Networking Lunch in the Exhibit Hall and Poster Viewing

13:00

Ymir GenomicsEV Isolation from Biofluids
Shannon Pendergrast, Chief Scientific Officer, Ymir Genomics

We will present several novel products and methods for the rapid and effective isolation of biofluid extracellular vesicles (EVs).

13:30

Chulhee ChoiKeynote Presentation

Exosome Engineering for Delivery of Cytosolic Proteins: Principles and Therapeutic Applications
Chulhee Choi, Professor and Chair, BioMedical Imaging Center, Korea Advanced Institute of Science and Technology (KAIST), President, Cellex Life Sciences, Korea South

Our group has recently developed an opto-genetically engineered exosome system, named ‘exosomes for protein loading via optically reversible protein–protein interaction” (EXPLOR) that can deliver soluble proteins into the cytosol of target cells via controlled, reversible protein–protein interactions (PPI). By integrating a reversible PPI module controlled by specific wavelength of light with the endogenous process of exosome biogenesis, cargo proteins of our interest can be loaded into newly generated exosomes. Protein-loaded exosomes were shown to significantly increase intracellular levels of cargo proteins and their function in recipient cells in both a time- and dose-dependent manner. In this presentation, I will introduce the basic principles of EXPLOR technology and follow-up studies for therapeutic applications including sepsis.

14:00

Induced Tissue Regeneration (iTR) Using Extracellular Vesicles
Dana Larocca, VP Discovery Research, AgeX Therapeutics, United States of America

There is a critical unmet medical need for new therapies to treat age-related diseases given the increasing burden of a global demographic shift toward older populations.  Extracellular vesicles (EVs) have been demonstrated to be largely responsible for the regenerative effects of stem cells in a variety of animal models of age-associated diseases including cardiovascular diseases.  We hypothesize that EVs made by cells from early human development will convey strong regenerative signals because this is when regenerative capacity is at its peak. We used partial differentiation of human pluripotent stem cells to derive a large library of highly scalable and clonally pure embryonic progenitor cell lines.  Over 200 progenitor lines were originally established to meet the high demands of cell purity and scalability needed to treat a large aging population.  We are now mining this diverse library of cell lines for their ability to provide a scalable source of highly regenerative EVs.  We found that embryonic progenitor derived EVs had higher angiogenic activity than adult stem cell derived EVs. Moreover, angiogenic activity was maintained by EVs produced by cells at up to at least 52 population doublings and following bioreactor scale-up.  We are currently mapping bioactivity and cargo of EVs derived from a variety of embryonic cell types including endothelial, pericyte, smooth muscle, osteochondral and brown adipocyte progenitors.  We anticipate that the resulting library of diverse embryonic EVs will be a valuable resource for developing EV therapies for cardiovascular and other age-related diseases.

14:30

Adipose-derived Stem Cell Extracellular Vesicles can be Specifically Tuned for Soft Tissue Repair and Wound Healing
John Ludlow, Executive Director, Regenerative Medicine, Zen-Bio, Inc., United States of America

Our research program is designed to provide critical proof-of-concept data demonstrating manufacturing conditions and wound healing properties of stem cell-derived extracellular vesicles.

15:00

The HSP-Accessorized Exosome: Presence in States of Danger, Disease, and Disruption
Michael Graner, Associate Professor, Dept of Neurosurgery, University of Colorado Anschutz School of Medicine, United States of America

Heat shock proteins (HSPs) function as chaperones under both normal and pathologic conditions. As chaperones they assist in protein folding, in holding protein complexes for current or future activation, and in the degradation of senescent proteins for recycling of components and display for immune surveillance. During stressful situations, HSP quantities and/or activities are increased as cells and tissues seek protection from insults. On occasion, these insults can result in the cell surface display of HSPs, which can then lead to the surface display of HSPs on exosomes, membrane-enclosed vesicles released extracellularly after passage thru the endosomal system. HSPs present on the cell surface or in the extracellular space are regarded as “danger signals” in an ancient biologic paradigm. HSP-accessorized exosomes may act as “danger boli”, carrying not only the HSPs, but hundreds of components of the stressed parental cell, capable of prompting immune responses, or possibly immune suppression, depending on the status of the recipient cell. Here we show that exosomes from the blood of patients suffering from neurologic maladies (cancer, brain injury, multiple sclerosis) are precipitated by peptides designed to bind HSPs. The metabolome of such exosomes is distinct from that of blood exosomes from healthy donors. Such HSP-accessorized exosomes possess inflammatory properties and may serve as biomarkers in a “liquid biopsy” setting.

15:30

Paul RobbinsConference Chair

Extracellular Vesicles and Aging
Paul Robbins, Professor, Department of Biochemistry, Molecular Biology, and Biophysics, and the Institute on the Biology of Aging and Metabolism, University of Minnesota Medical School, United States of America

16:00

Dominique PV de KleijnKeynote Presentation

Title to be Confirmed.
Dominique PV de Kleijn, Professor Experimental Vascular Surgery, Professor Netherlands Heart Institute, University Medical Center Utrecht, The Netherlands, Netherlands

16:30

Cell-to-Cell Propagation of Pathogenic Aberrant Dipeptide Repeat Proteins in C9orf72-Linked Amyotrophic Lateral Sclerosis
Davide Trotti, Professor, Scientific Director, Weinberg ALS Center, Vickie and Jack Farber Institute for Neuroscience, Thomas Jefferson University, United States of America

Nucleotide repeat expansions (NREs) are prevalent mutations in a multitude of neurodegenerative diseases. Abnormal translation of these repeat regions produces proteins that contribute to the pathogenesis of these diseases. However, the mechanisms and drivers of the aberrant translation are not well understood. Here we analyzed whether different cellular stressors promote these aberrant translations of peptides associated with the G4C2 hexanucleotide expansions in C9orf72, the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). We found that activating glutamate receptors or increasing neuronal activity trigger these aberrant translation of  neurotoxic peptides. In addition, we postulate that cell-to-cell transmission of these disease-linked aberrant peptides could be a modality by which toxic insults spread in disease-afflicted CNS areas in ALS and FTD. We are presenting evidence here using in vitro and in vivo approaches that indeed transmission of these aberrantly translated peptides occurs via exosomes and that transfer of injury could happen from the neuron of peptide formation to neighboring neurons but also to neurons connected in neuronal networks.

17:00

Extracellular Vesicles Go Nuclear
Aurelio Lorico, Professor of Pathology, Touro University Nevada, United States of America

Molecular mechanisms regulating EV biogenesis, their release, and subsequent uptake by target cells have emerged during the last two decades. How their cargo molecules are selectively delivered to their intracellular sites of action, including the intra-nuclear compartment, is still obscure. This issue is particularly important given that the biogenesis and functionality of EVs are dysregulated under pathological conditions. Recently, we described a novel sub-nuclear compartment which is created by the entry of small GTPase Rab7-containing late endosomes in the nucleoplasmic reticulum. The latter is shaped by superficial and deep nuclear envelope invaginations (NEI) penetrating into the nucleoplasm. Given that late endosomes in NEI has often an elongated appearance and resembles a sword in its scabbard, we proposed to name this dual-structure “spathasome” from Greek/Latin words “spathi/spatha” for sword. This structure appears to act as an intermediate compartment for the delivery of the content of endocytosed EVs (e.g., CD9/CD133 protein complexes and RNA molecules) to the nucleoplasm of their host cell. The NEI-associated late endosomes and nuclear localization of EV-derived proteins were observed in cancer cells and mesenchymal stromal cells in cultures and in breast cancer patient biopsies. A molecular complex, investigated by indirect immunofluorescence, fluorescence resonance energy transfer, immunoisolation techniques and RNA interference, was found to be responsible for the entry of EV cargo into the nucleoplasmic reticulum.


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