(2by) Engineering Instructive Vascular Tissues As Biological Models and Next-Generation Therapies

Communication between different cell types directs many fundamental biological processes, such as proliferation, migration, and differentiation. However, the key challenges in studying cell-cell communication lie in creating tissue models that capture the spatial organization of different cell types in in vivo tissue, as well as controlling the signaling cues that are transmitted between cell types within these models. Thus, my research program will combine principles from tissue engineering and synthetic biology/cell engineering to elucidate the axes of cell-cell communication that instruct tissue development, repair, or dysfunction, which will subsequently inform the development of novel therapies for regenerative medicine or diseases such as cancer. In doing so, my research program will build tissue models to investigate cell-cell communication, identify key signaling pathways that control tissue function and dysfunction, and design tissue therapies that control cell-cell communication to instruct regenerative and disease outcomes. Building upon my graduate and postdoctoral training, I am particularly interested in the role of vascular signaling in directing cell behavior within tissues. Thus, my lab will initially focus on developing and applying instructive vascular tissues to investigate the following:

1) The role of vasculature in brain development

2) The mechanisms by which vasculature instructs cancer metastasis

3) The influence of vascular signaling in post-stroke regeneration

Research Experience:

Synthetic regulation of vascular signaling, Department of Biomedical Engineering, Boston University (Advisor: Christopher S. Chen)

My postdoctoral research has focused on combining tools from tissue engineering and synthetic biology to control the formation of functional vasculature for ischemic therapies and engineered tissues. Vasculature is present in nearly every tissue in the human body, but vascular architecture and density vary from tissue to tissue in order to accommodate a wide range of metabolic and nutrient demands. Current technologies to generate vasculature are limited in their ability to control vascular density and generate long-lasting and perfusable vasculature. To overcome these limitations, I am engineering vascular cells with orthogonal and inducible genetic constructs in order to provide tunable control over the secreted signals that direct vascular assembly and stabilization. By combining these engineered cells with microfluidic models of vascularization, I am studying how the magnitude and timing of angiogenic and maturation signaling cascades are coordinated to give rise to functional vasculature with different densities and architectures. My work will yield fundamental insight into the signaling requirements for vascular morphogenesis and present a new paradigm for engineering tissues by controlling intercellular communication.

Developing in vitro models of the glioblastoma perivascular niche, Department of Chemical and Biomolecular Engineering, University of Illinois Urbana-Champaign (Advisor: Brendan A.C. Harley)

My dissertation research focused on developing biological models and experimental workflows for understanding the role of vascular signaling in cancer progression. Specifically, I established an engineered tissue model for the glioblastoma perivascular microenvironment. Glioblastoma (GBM) is the most common primary malignant brain tumor, with a median survival of one year. Many GBM tumor cells are found adjacent to blood vessels in a microenvironment called the perivascular niche; however, it is largely unknown how signaling from vascular cells within the perivascular niche impacts tumor cell behavior. My work revealed that combined signaling between endothelial and perivascular stromal cells creates a microenvironment that supports GBM invasion, the co-existence of fast- and slow-cycling cells, and resistance to temozolomide, the standard-of-care chemotherapy for GBM. Furthermore, my tissue model revealed the spatial organization of phenotypically-diverse sub-populations of tumor cells residing within the perivascular niche. Overall, my research provided important insight into the role of vascular signaling in GBM and particularly highlighted an crucial role for perivascular stromal cells, which have been historically neglected in tissue-engineered tumor-vascular models. In the future, my engineered tissue model can be used to design therapies to target aggressive tumor cell subpopulations within the perivascular niche.

Selected Publications:

• Ngo MT, Sarkaria JS, Harley BAC. Pericytes and astrocytes instruct vascular architecture and glioblastoma behavior within an artificial perivascular niche. In revision, Advanced Science.
• Ngo MT*, Barnhouse VR*, Gilchrist AE, Mahadik, BP, Hunter CJ, Hensold JN, Harley BAC. Hydrogels containing gradients in vascular density reveal dose-dependent role of angiocrine cues on stem cell behavior. Advanced Functional Materials. 2021; 2101541. *co-first author
• Ngo MT, Harley BAC. Progress in mimicking brain microenvironments to understand and treat neurological disorders. APL Bioengineering. 2021; 5;020902.
• Ngo MT, Harley BAC. Angiogenic biomaterials to promote therapeutic regeneration and investigate disease progression. Biomaterials. 2020; 255;120207.
• Ngo MT, Karvelis E, Harley BAC. Multidimensional hydrogel models reveal endothelial network angiocrine signals increase glioblastoma cell number, invasion, and temozolomide resistance. Integrative Biology. 2020; 12(6):139-49.
• Ngo MT, Harley BAC. Perivascular signals alter global gene expression profile of glioblastoma and response to temozolomide in a gelatin hydrogel. Biomaterials. 2019; 198:122-34.
• Ngo MT, Harley BA. The influence of hyaluronic acid and glioblastoma cell coculture on the formation of endothelial cell networks in gelatin hydrogels. Advanced Healthcare Materials. 2017; 6(22).

Selected Awards:

• Boston University Kilachand Postdoctoral Fellowship (2021 – 2023)
• University of Washington DYSS Speaker (2021)
• BMES Career Development Award (2020)
• Cell and Molecular Bioengineering (CMBE) Graduate Student Shooting Star Award (2020)
• MIT ChemE Rising Star (2019)
• University of Illinois School of Chemical Sciences Teaching Award (2018)
• National Science Foundation Graduate Research Fellowship (2016 - 2020)
• Illinois Distinguished Fellowship (2015 – 2020)

Teaching Interests:

Based on my undergraduate education in chemical engineering, I am qualified to teach core classes such as mass and energy balances, thermodynamics, separations, process control and dynamics, chemical reaction engineering and kinetics, fluid mechanics, and transport phenomena. From my teaching experience in graduate school, I have particular experience in instructing coursework related to fluid mechanics, transport phenomena, chemical reactor engineering, and kinetics. As a faculty member, I am additionally interested in developing electives related to biological transport phenomena, biomaterials, tissue and cellular engineering, or biological principles for engineers. Within my lab, my students will develop interdisciplinary expertise across biology, materials science, tissue engineering, and cell engineering/synthetic biology.

Teaching Experience:

• Kinetics and reactor design (Olivet Nazarene University), Guest lecturer (2019)
• Biotransport (Illinois ChBE), Teaching assistant (2019)
• Momentum and heat transfer (Illinois ChBE), Teaching assistant (2018)
• Chemical reaction engineering (Illinois ChBE), Teaching assistant (2017)

Diversity and Service:

Throughout my education, I have benefited from programs that focused on introducing under-represented minorities to career opportunities in STEM and provided mentoring to these students throughout their undergraduate and graduate education. Thus, as a faculty member, I am committed to participating in or developing initiatives that introduce STEM to K-12 students from under-represented backgrounds and provide mentorship to under-represented students during their undergraduate and graduate careers. At the University of Illinois, I participated in several activities that introduced STEM to K-12 students, such as the Girls’ Adventures in Math, Engineering, and Science summer camp and Young Scientist Day at Yankee Ridge Elementary School. Furthermore, I served as a mentor for the Sloan Scholars program, which provides support to under-represented graduate students in STEM. At Boston University, I am involved in the STEM Pathways program as a volunteer for K-12 outreach activities. As a faculty member, I intend to partner with K-12 schools that serve under-represented populations in order to provide STEM activities and opportunities to participate in summer research within my lab. Within my department, I will participate in or establish initiatives to support undergraduate and graduate students from all backgrounds, such as a “Women in Chemical Engineering” student organization or peer mentoring programs.