MxW Symposium 2024 | Speakers


Speakers

Discover the expertise of key opinion leaders and leading scientists at the MxW Symposium 2024 in Boston! Our speakers, pioneers in neuroscience, cell biology, and bioengineering, will share insights on iPSC-derived neurons, neural organoids, and MEAs. Learn more about their innovative talks and the impact on neuroscience research.

Confirmed Speakers:

Prof. Dr. Sofie Salama
University of California, Santa Cruz, USA
Keynote

Prof. Dr. Mircea Teodorescu
University of California, Santa Cruz, USA
Keynote

Prof. Dr. Pamela Abshire
University of Maryland, College Park, USA
Scientific Talk

Prof. Dr. Dai Akita
Takahashi Lab, The University of Tokyo, Japan
Special Online Short Talk & Dai Corner

Dr. An Ouyang 
ACROBiosystems
Company Talk

Dr. Wesley Clawson
Levin Lab, Tufts University, USA
Scientific Talk

Jessica Conley
Tim Shafer’s lab, U.S. Environmental Protection Agency, USA & ORISE, USA
Short Talk

Luke Foulser
bit.bio
Company Talk

Prof. Dr. Feng Guo
Indiana University Bloomington, USA
Scientific Talk

Dr. Matt Kelley
Alexion-AstraZeneca Rare Disease, USA
Scientific Talk

Daniel Rebbin
Institute for Interdisciplinary Studies, University of Amsterdam, Netherlands
Short Talk

Dr. Maria Sundberg
Sahin Lab, Boston Children’s Hospital/Harvard Medical School, USA
Scientific Talk

Dr. Abduqodir Toychiev
NeuroDiscovery Lab, Mitsubishi Tanabe Pharma America, Inc., USA
Scientific Talk

Prof. Dr. Julio Martinez-Trujillo 
Cognitive Neurophysiology Laboratory, Western University
Canada
Scientific Talk

Speaker Information – Scientific Abstracts & Short Bios:


Prof. Dr. Pamela Abshire
University of Maryland, College Park, USA


Title
| Top Ten Lessons Learned from Long Term Experiments with the MaxOne HD-MEA

Abstract | Over the past couple of years, our lab has transitioned from zero to daily use of multiple MaxOne platforms. We are using the system for long term recording and stimulation experiments to study network plasticity in 2D dissociated neuronal culture. In this talk I’ll briefly discuss some of the challenges that we’ve encountered and how we’ve handled them, including: spike detection, temperature, well size, artifacts, PDMS structures, long-term recordings, mixed cultures, phototoxicity, stagetop incubator, and routing of stimulation vs recording channels.

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Prof. Dr. Dai Akita
Takahashi Lab, The University of Tokyo, Japan


Title
| Showcasing interaction between neural culture and public audience

Abstract | Recent advances in information processing using neural cultures, such as gameplay and voice recognition, are attracting increasing interest. However, it is still rare for the general public to observe the real-time activity of living neurons and witness their responses to applied stimuli. We have developed an interactive interface that allows users to view artistically visualized neural activity and send stimulation commands through the chat interface of streaming platforms such as Zoom, YouTube, and others. The audience can experience the neural activity through light and sound effects triggered by neuronal spikes. The stimulation process is straightforward and intuitive: commands are sent as text messages and translated into stimulation sequences for 26 electrodes, each corresponding to a letter of the alphabet. In this short talk, we will briefly explain and demonstrate the system.

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Dr. An Ouyang
ACROBiosystems


Title
| Human iPSC-derived Cerebral Organoids as Neurodegenerative Disease and Neurotoxicity Models

Abstract | Current organoid technologies often lack certain physiological cell types and reproducible, translatable biological assays, despite being a promising advancement in drug development and disease modeling to combat high clinical drug failure rates, even after rigorous preclinical testing. At ACROBiosystems, we have developed novel, commercially available, hydrogel-free, consistent human iPSC-derived cerebral organoid systems. These cerebral organoids inherently contain several neuronal subtypes, astrocytes, oligodendrocytes, microglia, and endothelial cells, verified by bulk RNA-seq, scRNA-seq, and marker immunolabeling. Electrophysiological activity was recorded intracellularly by patch clamp and extracellularly by silicon probe insertion into the organoids. Furthermore, chemical and alpha-synuclein pre-formed fibril-induced models of Parkinson’s disease and small molecule and Tau pre-formed fibril-induced models of Alzheimer’s disease were generated on the cerebral organoids, recapitulating relevant disease-related phenotypes. We outline the use of ACROBiosystems’ human iPSC-derived organoids as an improved preclinical model for neurodegeneration and neurotoxicity to help provide better guidance for therapy development when moving into clinical research.

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Dr. Wesley Clawson
Levin Lab, Tufts University, USA


Title
| Training Tissue Through Closed Loop Virtual Embodiment

Abstract | Biological systems’ most fundamental ability is learning. However, how tissue-wide goal-seeking behavior orchestrates reorganization remains unknown. Using the MaxWell Biosystems CMOS HD-MEAs, we engineered a closed-loop experimental paradigm that allows for the training of neural tissue culture through embodiment in virtual spaces, such as a 1D track. We have successfully embodied culture in two paradigms. First, we trained neural cultures’ bursting behavior, when neurons fire synchronously for a short time, to preferentially burst from specific regions of the culture. Second, we allowed the cultures to navigate a track where regions along the track correspond to different feedback frequencies. While still proof-of-concept – this engineered, synthetic experimentation offers unprecedented insights detached from in vivo complexity, and observation throughout training has the potential to unveil general principles of unconventional learning and plasticity.

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Jessica Conley
Tim Shafer’s lab, U.S. Environmental Protection Agency, USA
Oak Ridge Institute for Science and Education (ORISE), USA


Title
| A New Approach Methodology (NAM) using Human iPSC-derived BrainSpheres for Developmental Neurotoxicity Screening

Abstract | Exposure to environmental compounds during neurodevelopment can cause adverse morphological and/or functional changes in the developing brain, and new, human based models are needed to investigate the potential developmental neurotoxicity (DNT) of environmental compounds. To investigate these effects, human induced pluripotent stem cell-derived neural spheroid models have been utilized due to their ability to form mature neural populations that exhibit spontaneous electrical activity.
We have used high-density microelectrode array recordings to characterize the ontogeny of spontaneous electrical activity in a human neurospheroid model and study the impacts of chemical exposure on the development of that activity. Our results show that compounds known to disrupt network formation in other in vitro models, also disrupt the formation of neural networks in human neurospheroids. These results indicate this model could be a valuable addition to existing in vitro approaches for DNT screening.
Future studies will expand testing of environmentally relevant compounds to demonstrate further the capability of this approach for DNT screening. This abstract does not represent US EPA policy.

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Luke Foulser
bit.bio


Title
| Utilising Functional Human iPSC-Derived Neurons as a Robust Foundation for generating consistent, physiologically relevant HD-MEA Assays

Abstract | High-density microelectrode arrays (HD-MEAs) are a powerful tool to measure the electrophysiological properties of human neurons in vitro, and are a cornerstone method in the development of new therapeutics for neurological diseases. High-density electrophysiology experiments that produce publishable, translatable data rely on high-quality, functional, and physiologically relevant cells as input.
bit.bio has developed opti-ox™, an iPSC reprogramming technology that enables the consistent generation of defined, mature, functional human cell types at scale.
In this talk, we will explore how the MaxWell MaxTwo HD-MEA system has been used in the functional characterisation of opti-ox precision reprogrammed ioMotor Neurons, ioGlutamatergic Neurons™, and ioSensory Neurons™.
We dive into data generated on the MaxWell MaxTwo characterising the electrophysiological properties of these three cell types and show how their properties are aligned with their known biological function. We will also discuss how you could use ioCells™ to set up similar experiments with a MaxTwo system in your own lab.

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Prof. Dr. Feng Guo
Indiana University Bloomington, USA


Title
| Brain Organoid Computing for Artificial Intelligence

Short Bio | Dr. Feng Guo is an Associated Professor of Intelligent Systems Engineering at Indiana University Bloomington (IUB). Before joining IUB in 2017, he received his Ph.D. in Engineering Science and Mechanics at Penn State and his postdoc training at Stanford University. His group is developing intelligent medical devices, sensors, and systems with the support of multiple NIH and NSF awards. He is a recipient of the NIH Director’s New Innovator Award, the Outstanding Junior Faculty Award at IU, Early Career Award at Penn State, the Dean Postdoctoral Fellowship at Stanford School of Medicine, etc.

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Dr. Matt Kelley
Alexion-AstraZeneca Rare Disease, USA


Title
| Progressing neuroscience drug discovery through HD-MEAs

Abstract | High-density microelectrode arrays (HD-MEAs) are a powerful, emerging technology in neuroscience drug discovery. These arrays enable simultaneous, non-invasive, real-time monitoring of electrical activity from neurons at scale, offering a detailed perspective on network dynamics and individual neuron functionality, including axon physiology. We will discuss various use cases of HD-MEAs in drug discovery research featuring ex-vivo and in-vitro preparations. The presentation will include the introduction of a human model of Dravet syndrome, developed using patient induced pluripotent stem cell (iPSC) derived neurons and characterized by HD-MEAs. We will discuss how our spike sorting analysis pipeline enables high throughput assessment of neuronal response to an ion channel potentiator. The primary aim of this presentation is to explore the current applications and next steps of HD-MEA technology in the realm of drug discovery research, emphasizing its potential to bring value to the development of novel treatments for patients with neurological disease.

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Daniel Rebbin
Institute for Interdisciplinary Studies, University of Amsterdam, Netherlands


Title
| Synergies Between Ephaptic and Synaptic Signals Bias Neural Self-Organization

Abstract | With the hype around AI currently unfolding, the connectionist assumption that cognitive processes can be boiled down to the manipulation of synaptic weight matrices seems more popular than ever before. However, this growing paradigm casts an ever larger shadow on the compelling literature suggesting that ephaptic, i.e. field-mediated, coupling seems to play a decisive role for the temporal dynamics at a network level, which can be easily overlooked due to its seemingly marginal impacts at a single-cell level. Considering the physical constraints imposed by free energy minimisation on neural self-organization, we test a parsimonious explanation for the empirical network properties brain organoids on a high-density multielectrode array (HD-MEA): As the synaptic and ephaptic signals emitted from an oscillatory source propagate at different speeds, their spatial cross-correlation is biasing neural self-organization in an overlooked way. Specifically, the constructive interference between these two signals during gamma bursts allows for the gradual emergence of neural clusters. This novel perspective promises a fruitful avenue to reconcile the analogue and digital aspects of neural computation.

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Prof. Dr. Sofie Salama
University of California, Santa Cruz, USA

Prof. Dr. Mircea Teodorescu
University of California, Santa Cruz, USA


Title
| Modular Open Source Systems for Longitudinal Culturing and Characterization of Brain Tissues?

Abstract | This presentation will explore the development and validation of several IoT-enabled platforms designed for longitudinal culturing of biological samples, with direct application to brain cortical organoids. These employ sensing (e.g., computer vision and electrophysiology), automatic microfluidics feeding and control for media volume regulation to enhance in vitro experiment consistency. Our MaxOne integrated system maintained robust neural activity throughout multi-day experiments, comparable with the control samples. Furthermore, the automated system enables hourly electrophysiology recordings that revealed dramatic temporal changes in organoid neuron firing rates not observed in once-a-day recordings. Finally, in this system media changes do not appear to affect neuronal activity.

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Dr. Maria Sundberg
Sahin Lab, Boston Children’s Hospital/Harvard Medical School, USA


Title
| Characterization of pathogenic variants of KCNQ2 channel in Human iPSC-derived glutamatergic neuron networks

Abstract | The KCNQ2 gene is located on chromosome 20q13.33, and it encodes a member of the potassium voltage-gated channel subfamily Q that encodes Kv7.2 protein subunits. KCNQ2 channel regulates neuronal excitability and action potential firing. Variations in this gene may cause seizures, epileptic encephalopathy, developmental delay, and autism. Several pathogenic KCNQ2 variants have been identified in patients, but their disease phenotypes and functionality have not been fully characterized at the cellular level.
To investigate the cellular pathophysiology associated to KCNQ2 variants, we used iNGN2 expression to generate cortical glutamatergic neurons from patient-derived iPSCs. In order to generate isogenic control lines, we utilized CRISPR-Cas9 gene editing technology to correct the KCNQ2 variants in these iPSC lines. The disease phenotypes in the patient derived neurons were then characterized using various molecular biology and functional assays. Synaptic marker expression was quantified with immunocytochemistry, neurite growth was measured using time-lapse imaging, and RNA sequencing was used for transcriptional profiling. Importantly, we have utilized the MaxTwo HD-MEA to investigate the functional disease phenotypes of these patient-specific KCNQ2-variant neuronal networks, including network firing rate, bursting phenotypes, and axon tracking features.

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Dr. Abduqodir Toychiev
NeuroDiscovery Lab, Mitsubishi Tanabe Pharma America, Inc., USA


Title
| Functional characterization of induced pluripotent stem cells in patients with amyotrophic lateral sclerosis with TARDBP mutation

Abstract | Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by motor neuron degeneration leading to muscle weakness and eventual death. Early signs of ALS include muscle twitching, cramps, stiffness, and weakness. As the disease advances, individuals may experience slurred speech, difficulties chewing and swallowing, and, in some cases, cognitive decline. The primary aim of current therapies is to slow disease progression rather than restore neuronal function. To help pave the way for future therapeutic strategies, this study focused on understanding fundamental alterations in ALS neurons with TARDBP mutations. Using single-cell electrophysiology and high-density microelectrode arrays, we identified significant changes in firing rates, action potential activity, neuronal hyperactivity, and network dynamics in neurons derived from induced pluripotent stem cells (iPSCs) of patients with ALS and the TARDBP mutation compared to patients with ALS absent this mutation. These changes were particularly pronounced during neuronal stimulation and modulation by synaptic blockers. Our findings offer crucial insights into the pathological mechanisms of ALS motor neurons, helping to provide the foundational understanding necessary for development of targeted treatments.

Authors: Abduqodir Toychiev, PhD; Makoto Tamura, PhD
Disclosure: AT and MT are employees of NeuroDiscovery Lab, Mitsubishi Tanabe Pharma America, Inc.
Sponsorship: This study was sponsored by Mitsubishi Tanabe Pharma America, Inc.
Acknowledgments: Editorial support was provided by p-value communications. This support was funded by Mitsubishi Tanabe Pharma America, Inc., Jersey City, NJ, USA, in accordance with Good Publication Practice Guidelines 2022.

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Prof. Dr. Julio Martinez-Trujillo
Cognitive Neurophysiology Laboratory, Western University, Canada


Title
| A neurometric approach to study iPSC derived networks development

Abstract | Over the last decade an accelerated development in induce pluripotent stem cell (iPSC) technologies and gene editing has allowed differentiation of human iPSCs into neurons and further into 2-D neuronal networks and 3D brain organoids. Neurons committed to the neural lineage fire action potentials and make synaptic connections that resemble the ones in developing brains. Such networks composed of thousands of neurons produce patterns of brain activity that evolve over time and have been described as network bursts. Network bursts can be diverse depending on the developmental period of the network and specific gene mutations. Characterization of single neurons responses and network activity patterns including bursts via multielectrode (MEA) recordings has proven to be a valid method to examine the effect of genetic manipulation and rescue interventions in network activity patterns. Here I present data from low- and high-density MEA recordings of hiPSC derived neuronal networks containing mutations of the MECP2 and SHANK2 genes. I present novel measurements using function fitting on neural activity data that provide a parametrization of network connectivity development. Our results highlight the importance of increasing the spatial and temporal resolution of electrophysiological measurements to reveal important details of how network connectivity develops over time.

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