2023 Organizing Committee

Lead Organizers: Gillian McMahon, Challana Tea

Speaker Recruiter: Sreejith Santosh, Camilo Rey Bedón

Biotech Liaison: Ayooshi Mitra, Simar Sharma

Outreach Coordinator: Abhinaba Banerjee, Aishwarya Balaji

Grant Writer: Erin LaMontagne

Welcome Greeter: Jolene Lei, Subhash Arumugam

Catering Coordinator: Sara Herrera de la Mata, Joycelyn Yiu

Registration begins at 8:30 am

Sign in outside Kavli Auditorium (TATA Hall 3rd floor)

9:30 am: Introductory speaker

Abstract

The human brain has many features that are distinct to humans. To effectively understand human disease mechanisms and identify novel therapies, it is critical to have access to a human tissue-based model for experimental study. In vitro models, termed human brain organoids (aka “mini-brains in a dish”) are three-dimensional (3D) tissue structures induced from human pluripotent stem cells (hPSCs) that recapitulate key aspects of human neurodevelopment. Human monolayer cell culture has been one approach; however, it cannot fully mimic 3D architecture, which is likely important for predicting clinical outcomes and finding effective drugs. However, existing organoid models suffer from a lack of cell diversification and a need to assemble distinct regions that normally develop together in vivo. We have developed brain organoids that closely mimic the human fetal cortex transcriptionally, architecturally, and functionally.  Here, we demonstrate a novel organoid platform capable of growing multiple domains of the telencephalon together without need for assembly.

Bio

Dr. Watanabe earned a B.S. in Molecular, Cell, and Developmental Biology from the University of California, Los Angeles (UCLA) in 2006. She then pursued her doctoral studies at UC Irvine, where she studied the mechanisms of forebrain patterning and used in vivo developmental principles to derive choroid plexus epithelial cells from mouse and human pluripotent stem cells (PSCs) for cell-based therapeutic applications. Building on her excitement and experience with neural development and stem cell biology, she did her first post-doctoral training at RIKEN Center for Developmental Biology in Japan, to focus on the three-dimensional culture of cerebral cortex structures, so called brain organoids, generated from hPSCs. She then moved back to the U.S. and joined UCLA. Her project focused on the development of highly efficient and reproducible cerebral organoid methods to investigate the origins of cortical neural circuits and model neurodevelopmental disorders, including the Congenital Zika Syndrome. Building upon these accomplishments, she successfully received a NIH K99/R00 grant from the National Institute of Child Health and Human Development (NICHD). She was recently recruited to UC Irvine as a part of Faculty Hiring for Leveraged Research Excellence (FHLRE) “Stem Cells in Tissue Engineering” and started as an Assistant Professor at the Anatomy and Neurobiology Department in 2020. She is very excited to contribute to a synergistic interdepartmental concentration in stem cell-based engineering.

Abstract

This talk focuses on the recent advances in microscale bioprinting technology developed in our lab. Using a range of biomaterials and cells, 3D tissue models are created with precise control over their micro-architecture, mechanical, chemical, and biological properties. The bioprinted tissues enable investigation of cell-microenvironment interactions in response to integrated stimuli, leading to the development of Organ-on-a-Chip models for disease modeling and drug discovery. The presentation will delve into the engineer's perspective on design innovation, biomaterials selection, and scalable biomanufacturing, showcasing examples of liver, heart, and tumor models.

Bio

Dr. Min Tang received her Ph.D. in Nanoengineering from the University of California, San Diego, and holds a Master's and Bachelor's degree in Biomedical Engineering from Columbia University and Saint Louis Washington University, respectively. Her current research focuses on the application of biomanufacturing technologies, specifically 3D bioprinting, in the fields of tumor microenvironment studies and tissue engineering. During her postdoctoral training at UC San Diego, she expanded her research to include the evaluation of immunotherapy efficacy and the establishment of a blood-brain barrier model for more realistic drug testing for brain tumors. These studies have resulted in the publication of 16 peer-reviewed articles in journals such as Cell Research, Advanced Materials, Nucleic Acid Research, Small, and Biomaterials. Additionally, Dr. Tang has contributed to writing chapters in two books on 3D bioprinting. Her development of a 3D bioprinted brain tumor immune model was highlighted as a new tool in developmental biology and tumor research by Nature in April 2021.

Abstract

Pluripotent stem cell-derived organoids have transformed our ability to recreate complex three-dimensional models of human tissue. However, the directed differentiation methods used to create them do not afford the ability to introduce cross-germ-layer cell types. Here, we present a bottom-up engineering approach to building vascularized human tissue by combining genetic reprogramming with chemically directed organoid differentiation. As a proof of concept, we created neuro-vascular and myo-vascular organoids via transcription factor overexpression in vascular organoids. We comprehensively characterized neuro-vascular organoids in terms of marker gene expression and composition, and demonstrated that the organoids maintain neural and vascular function for at least 45 days in culture. Finally, we demonstrated chronic electrical stimulation of myo-vascular organoid aggregates as a potential path toward engineering mature and large-scale vascularized skeletal muscle tissue from organoids. Our approach offers a roadmap to build diverse vascularized tissues of any type derived entirely from pluripotent stem cells.

Bio

Amir Dailamy received his B.S in Bioengineering from the University of California, Los Angeles in 2017. Currently, he is a Ph.D. candidate at UCSD in the department of Bioengineering in Dr. Prashant Mali's lab. His research interests include leveraging innate developmental processes for developing novel ways to engineer implantable organ tissues at scale.

Lunch

A vegan lunch will be provided, this is also an opportunity to network with other attendees and talk with our industry sponsors.

Abstract

The Vascularized Micro-Tumor (VMT) is a novel 3D model system that recapitulates the human tumor microenvironment within a transparent microfluidic device that allows for real-time imaging. The tumors include perfused vasculature, stromal cells and a complex matrix, allowing for analysis of drug responses in the context of tumor-stromal interactions. Importantly, all nutrients and drugs reach the tumor through living, human blood vessels. We are now incorporating fresh, patient-derived colorectal cancer (CRC) tumor tissue, and have optimized protocols for tumor survival and growth. CRC is the second leading cause of cancer-related deaths in the US. We find that the tumors show heterogeneous responses to standard-of-care drugs, however some respond to experimental drugs. The VMT provides a greatly improved model system for understanding the complexity of human CRC, including heterogeneous responses to drug therapies.

Bio

Dr. Hughes is a faculty member in the Department of Molecular Biology and Biochemistry and recently stepped down as chair after serving for 10 years. He is also a faculty member in Biomedical Engineering and served for 5 years as Director of the Edwards Lifesciences Center for Advanced Cardiovascular Technology in the Henry Samueli School of Engineering. He also served for over ten years as co-director of the Onco-Imaging and Biotechnology Program, part of the Chao Family Comprehensive Cancer Center at UCI. Professor Hughes’ research focuses on the development and growth of blood vessels. The work in his lab spans multiple scales – from understanding the basic molecular mechanisms of angiogenesis (the growth of new blood vessels) to the engineering of artificial tissues. Recently his lab has been pioneering “Body-on-Chip” technology, which allows for micro-organs – heart, pancreas, tumor, etc. – to be grown in the lab, each with its own blood vessel network. These “Vascularized Micro-Organ” and “Vascularized Micro-Tumor” devices are set to revolutionize how we screen for new therapeutic drugs, and the technology is now licensed to Aracari Biosciences, of which Dr. Hughes is a founder, and for which he serves as CSO. Professor Hughes has published over 100 peer-reviewed research manuscripts, in some of the world’s top science journals. In recognition of his outstanding research and publication record, he was elected as a Fellow of the American Association for the Advancement of Science (AAAS) in 2014. In addition to his research, Professor Hughes works extensively with the non-profit organization, cureHHT, which provides patient support and research advocacy on behalf of those suffering from the rare vascular disorder Hereditary Hemorrhagic Telangiectasia. Professor Hughes served for 8 years as Chair of the foundation’s Global Research and Medical Advisory Board and now chairs its North American Scientific and Medical Advisory Council.

Abstract

Patient-derived xenografts (PDX) and organoids (PDO) have been shown to model clinical response to cancer therapy. However, it remains challenging to use these models to guide timely clinical decisions for cancer patients. Here we used droplet emulsion to rapidly generate thousands of Micro-Organospheres (MOS) from low-volume patient tissues, which serve as an ideal patient-derived model for clinical precision oncology. A clinical study of newly diagnosed metastatic colorectal cancer (CRC) patients using a MOS-based precision oncology pipeline reliably predicted patient treatment outcome within 14 days, a timeline suitable for guiding treatment decisions in the clinic. Furthermore, MOS capture original stromal cells and allow T cell penetration, providing a clinical assay for testing immuno-oncology (IO) therapies such as PD-1 blockade, bispecific antibodies, and T cell therapies on patient tumors. Lastly, we demonstrate an ultra high-throughput MOS screening platform that provides “virtual clinical trials” to capture patient diversity for determining drug efficacy.

Bio

Dr. Shen is currently a professor and the chief scientific officer of the Terasaki Institute for Biomedical Innovation and the founder and chief executive officer of Xilis Inc, which raised an $89M Series A to advance precision medicine. He was formerly the Hawkins Family Associate Professor in the Department of Biomedical Engineering and the director of the Woo Center for Big Data and Precision Health at Duke University. He received his BS, MS, and PhD degrees from Stanford University and the NSF career award at Cornell University. He was the steering committee chair of the NCI Patient-Derived Model of Cancer Consortium, co-chair of the NCI Tissue Engineering Consortium, and cancer track chair of Biomedical Engineering Society 2019. His lab studies precision medicine from a systems biology perspective. Areas of interest include cancer, stem cells, the gut-brain axis, and microbiome.

Coffee break

Abstract

Organ-on-a-Chip technology has been proven to predict human response better than animal and conventional cell culture models. This session will focus on the use of the Emulate Liver-Chip to predict drug-induced liver injury (DILI) resulting from small molecules identified as benchmarks by the Innovation and Quality (IQ) MPS consortium. The Liver-Chip met the qualification guidelines across a blinded set of 27 known hepatotoxic and non-toxic drugs with a sensitivity of 80%, increasing to 87% when protein binding is corrected, and a specificity of 100%. 

Bio

Dr. Mahajan earned a Bachelors in Biotechnology Engineering from UIET, Panjab University, India and PhD in Biomedical Engineering from Cleveland State University in collaboration with Cleveland Clinic. His postdoctoral Fellowship in the Ingber’s lab at Wyss Institute, Harvard University was focused on developing clinically relevant organ-on chip models to evaluate efficacy and toxicity of various drug candidates, probiotics and adjuvants for vaccine development. In his current role at Emulate as a Scientific Liaison, his efforts are focused on adoption of the technology. So far, Gautam’s work has resulted in more than 20 peer-reviewed publications in reputed journals such as Nature Communications, Biophysical Journal and Biomaterial Sciences, and 20 conference and seminar presentations. 

Abstract

Qureator: Innovative and versatile Microphysiological Systems with HTS capability

During the past decades, scientists and engineers made significant progress in the production of user-friendly Microphysiological Systems (MPS). The key features of MPS are growing physiologically relevant cells embedded in physiological Extracellular Matrix (ECM) and co-cultured with physiologically relevant neighboring cells. Qureator has maintained the key principle of MPS features, but improved MPS by following our ARCH principles: Adoptability, Reproducibility, Customizability and HTS compatibility. This presentation will discuss the architectures of Qureator’s MPS, broad biological applications and recent advances in building a HTS infrastructure at Qureator including in-house developed imaging analysis programs.

Ethics and commercialization panel