(4ah) Microscale Tissue Engineering to Study Vascular-Immune Crosstalk in Cancer

The overarching goal of my research is to advance our physicochemical understanding of tumor immune microenvironments (TIME) in regulating vascular-immune interaction in cancer. The vision for my future research program is to develop unique cancer bioengineering approaches that integrate microscale technologies, hydrogel biomaterials, tissue engineering principles, and spatial omics tools to study vascular-immune system in TIME. These microengineered models will spatially pattern cellular compartments, mimic important physicochemical cues, and quantitatively characterizes the cellular behaviors and extracellular matrix (ECM) properties. My lab will focus on studying physicochemical mediators in disease progression, such as brain cancer, vascular basement membrane (BM) in TIME, and endometrium diseases (e.g., endometrial cancer) to advance human health.

Cancer creates a heterogeneous ecosystem where cancerous cells coexist with vascular and immune cells in a complex TIME. The key limitations of current experimental tools for studying vascular network and immune systems in TIME are incapable of controlling multiple physical and chemical (or physicochemical) parameters, which are necessary to deconstruct and resolve the instructive signals that are intrinsic to physiological settings. These instructive physicochemical mediators include ECM composition and structure, biomolecular gradient, oxygen tension, and mechanical signals. Despite widespread attention, there is still a lack of understanding of the complex interplay between angiogenic function and mediators of immunomodulation during cancer progression. The emergence of microscale engineered models that integrate biological elements with quantitative engineering tools provide unique capabilities to reconstitute essential structure complexity and important biological functions of tissue microenvironments similar with that found in vivo. Moreover, the unique attributes of microscale engineered models enable incorporating hydrogel biomaterials to modulate biochemical functions and biophysical properties for multicellular patterning, recapitulating barrier function, and applications of fluid flow. My independent research program will center on advancing microengineered models to study physicochemical regulators in controlling angiogenic function and immune responses in cancer progression and disease developments. Furthermore, my future research will also explore new frontiers to apply spatial analytical technology (e.g., spatial omics) and machine learning tools to study molecular, cellular and microenvironmental information at spatial and temporal scales in the microengineered tissue models.

My research is driven by my interdisciplinary research training which equipped me with the capability of applying engineering tools to address important biological questions. My PhD work at the Ohio State University (with Dr. Jonathan Song) combined principles from microsystems with tissue engineering to fabricate microfluidic tissue analogues for studying angiogenesis and lymphangiogenesis mediated by ECM biophysical properties and interstitial flow. My postdoctoral research at University of Illinois Urbana-Champaign (with Dr. Brendan Harley) centered on studying matrix invasion pattern of microglia and tumor-immune crosstalk in glioblastoma (GBM) using tissue-engineered models. The long-term vison of my lab is to unravel the principles that physicochemical cues govern the interlay of angiogenic function and immunomodulation that drive disease progression to improve human health. My lab will initially work on these three research areas.

Focus 1. Develop in vitro microphysiological brain immunological models of to elucidate tumor-immune-vascular crosstalk in brain cancer and brain immunology

Focus 2. Fabricate cell-derived ECM to study mechanobiology of vascular basement membrane in tumor microvascular niches

Focus 3. Explore physicochemical cues-regulated vascular-immune interactions (e.g., interstitial flow and ECM mechanobiology) in regulating endometrial development and diseases

Selected Publications

• Chia-Wen Chang, Hsiu-Chen Shih, Marcos G. Cortes-Medina, Peter E. Beshay, Alex Avendano, Alex J. Seibel, Wei-Hao Liao, Yi-Chung Tung*, Jonathan W Song*. “Extracellular Matrix-Derived Biophysical Cues Mediate Interstitial Flow-Induced Sprouting Angiogenesis” ACS Applied Materials & Interfaces, 2023, 15, 12, 15047–15058
• Chia-Wen Chang, Alex J. Seibel, Alex Avendano, Marcos G. Cortes‐Medina, Jonathan W. Song “Distinguishing Specific CXCL12 Isoforms on Their Angiogenesis and Vascular Permeability Promoting Properties” Advanced Healthcare Materials, 2020; 9; 1901399
• Chia-Wen Chang, Chien-Chung Peng, Wei-Hao Liao and Yi-Chung Tung*, "Polydimethylsiloxane SlipChip for mammalian cell culture applications" Analyst, 2015, 140, 7355-7365
• Chia-Wen Chang, Yung-Ju Cheng, Melissa Tu, Ying-Hua Chen, Chien-Chung Peng, Wei-Hao Liao and Yi-Chung Tung*, "A Polydimethylsiloxane-polycarbonate Hybrid Microfluidic Device Capable of Generating Perpendicular Chemical and Oxygen Gradients for Cell Culture Studies" Lab on a Chip, 2014, 14 (19), 3762-3772
• Chia-Wen Chang, Meng-Jiy Wang*, “Preparation of Microfibrillated Cellulose Composites for Sustained Release of H₂O₂ or O₂ for Biomedical Applications” ACS Sustainable Chemistry & Engineering, 2013, 1 (9), 1129-1134

Award and Honors

• The Best Poster Award, 12^th World Biomaterials Congress, Daegu, Korea, 2024
• Pelotonia Graduate Fellowship, OSU Comprehensive Cancer Center, USA, 2017
• CHI MEI Corporation Outstanding Talent Scholarship, Taiwan, 2012
• The Best Undergraduate Research Project Award, NTUST, 2011
• Presidential academic award (Top 5% in department), NTUST, 2018 - 2010

Teaching Interests

My teaching philosophy is to create an open and safe environment that fosters all levels of learners to explore. I believe that the most effective learning occurs in the environments that encourage student curiosity, practice, and collaborative teamwork. Based on my sound academic background in undergraduate and graduate level chemical engineering training, I am qualified to teach core courses, such as Chemical Engineering Principles, Thermodynamics, Transport Phenomena, Chemical Reaction Engineering, Separation Process, and Process Control and Dynamics. Particularly, I am interested in instructing courses related to fluid mechanics, transport phenomena, and mass and energy balances because these are in line with my prior teaching experience and my research in biomedical microfluidics. When teaching in undergraduate core courses, I will emphasize the importance of effectively communicating these fundamental concepts and knowledge in chemical engineering into solutions for technological and societal challenges. Embedding these practical applications in my lecture materials could significantly stimulate students’ curiosity and motivation to promote their learning outcomes. When teaching advanced graduate courses, I will expand my instruction from lecture-based materials to a modulus that mixed the depth content of coursework in biomedical engineering with topical literature discussion in adjacent fields.

Additionally, I am interested in developing new elective courses related to biological transport, microfabrication, biomaterials, immunoengineering and cancer bioengineering. This course would explore engineering principles (including experimental design, engineering tools and quantitative data analysis) in microscale biological transport, tissue engineering, immunology, and cancer. This elective would contain a mix of lecturing, coursework, literature presentation and final projects to provide engineering students an extra exposure to biological and cancer research.

I also value teaching as the fantastic opportunities to shape the future society. I strive to provide a multitude of applicable resources to ensure equal learning experiences in addressing classroom diversity. Moreover, I will actively recruit the future pipeline and train next generation of chemical engineers from historically excluded communities.