(4hl) Developing Vascularized Microphysiological Systems for Disease and Immunology Studies

Microphysiological systems (MPSs) have become essential tools for replicating the complex structures and functions of tissues and organs, offering significant advantages over traditional 2D cell cultures and animal models for disease modeling, drug development, and therapeutic research. However, current MPS models often fail to achieve the levels of vascularization seen in vivo, limiting their effectiveness. The immune system's role in protecting against foreign antigens is also critical for advancing disease therapies. My research focuses on immunology and the creation of vascularized MPSs for disease studies.

During my postdoctoral tenure, I developed several innovative approaches to generate perfusable, physiologically relevant microvessels in vitro. These include immortalized vascular cells (Wan et al., 2021), endothelial cells derived from induced pluripotent stem cells (iPSCs) using a doxycycline-inducible ETS Variant Transcription Factor 2 (ETV2) protocol (unpublished), a novel two-step seeding method (Wan et al., 2022b), and a new method employing interstitial flow to enhance vasculogenesis (Zhang et al., 2022). To improve the vascularization of tumor spheroids, I devised a sequential method that enhances fibroblast density and a novel microfluidic device that promotes endothelial cell penetration into tumor masses (Wan et al., 2022a). Using this model, I studied CAR-T cell responses and PD-L1 regulation by trans-endothelial flow within the tumor microenvironment (Wan et al., 2024). Additionally, our research tackles the challenge of establishing perfusable vasculature within engineered liver tissues (unpublished).

During my Ph.D., I explored how mechanical cues, such as substrate stiffness and mechanical forces, affect B lymphocyte activation and function (Wan et al., 2013;Wan et al., 2015;Shaheen et al., 2017;Wan et al., 2018). I also utilized advanced live-cell imaging systems and a photo-activatable antigen-presenting system to investigate B cell receptor activation features (Wan and Liu, 2012;Tang et al., 2016).

My research interests are centered on engineering perfusable vascularized tissues for disease and immunology studies. My future research directions include: 1) Developing perfusable vascularized organoids from various tissue types for studies on inflammation and organ-specific metastasis. 2) Creating advanced vascularized tumor-on-a-chip models to investigate immunotherapies, including chimeric antigen receptor (CAR) therapy. 3) Establishing an in vitro tertiary lymphoid structure (TLS) model to study its function in cancer or chronic inflammation conditions. 4) Using vasculature-on-a-chip models to study infectious diseases such as Zika, malaria, and HIV.

Teaching Interests: I have monitored 10 graduate students, 9 undergraduate students, and 1 high school student. I have also completed several teaching workshops. I trained over 20 people with confocal microscopy. Additionally, I have completed several teaching workshops and trained over 20 individuals in confocal microscopy. My teaching interests are informed by my interdisciplinary background in biology, biochemistry, immunology, and biological and mechanical engineering, as well as my extensive experience with wet lab techniques, microscopy, and microfluidic experiments. I am enthusiastic about teaching related courses and hands-on classes.

In summary, my interdisciplinary background, robust research achievements, innovative research directions, and extensive mentoring and teaching experiences make me a strong candidate for a faculty position.