Aim
We design and develop innovative integrative micro-technologies for the spatio-temporal control of extrinsic cell microenvironments and intrinsic 3D cell organization. We aim at understanding how biochemical-biomechanical specifications of local cellular environment and 3D spatial arrangement of organelles within the cell affect cellular functions and cell differentiation towards specific human tissues.
Significance
The elucidation of the intricate 3D structure-function relationship in human tissues is certainly a critical issue for a deeper understanding of the physiological and physio-pathological processes. These new insights provide fundamental knowledge to micro-engineering human in vitro models, which could represent a complementary tool bridging the gap between conventional cell culture, animal models and patients.
The human artificial tissues “on-a-chip” provide significant perspective in understanding cardiovascular diseases, diabetes, degenerative diseases as well as new platforms for a new integrative approach for drug design, screening, and validation in vitro.
Research project
Control of cell three dimensionality
The physical and mechanical cell microenvironment is emerging as a master regulator of cell functions from embryonic development to adult tissue homeostasis. Consequently, defects in cell shape, cell geometry or mechanotransduction process - the translation of mechanical forces into biochemical signaling within cells - are often implicated in the development of pathologies such as cancer and cardiovascular disease.
This research project will be focus on how cell shape and 3D spatial arrangement of interconnected organelles affects cellular functions and, in particular, nuclear function. We will focus on a structural hypothesis that postulates that altered cell and nuclear shape impairs nuclear organization, chromatin remodeling and gene expression.
This project is of high impact on different fields: stem cell (developmental process involves substantial nuclear and cell rearrangement), cancer (altered shape and structure are related to loss of cellular function), and immune system (which is a highly plastic system with strong nuclear remodeling).
Micro-engineering human in vitro models
We will focus on the development of in vitro models of human tissues mimicking the specific spatial arrangement of cells and extracellular matrix proteins, peculiar of their structure and function in vivo.
In particular, we hypothesized that the control of endogenous signaling pathways through the modulation of their extrinsic components can have a strong impact on both cell reprogramming and programming processes. The distinctive properties of microfluidics allow spatio-temporal control of cell culture microenvironment, enabling scale-down of somatic cell reprogramming as well as biomimetic developmental processes, from germ layer specification and phenotypic differentiation to tissue morphogenesis.
Understanding the molecular mechanisms that underlie extrinsic self-regulation of reprogramming/programming is crucial for high-quality derivation of specific cell phenotypes.
Developing advanced biomaterial platforms for cancer research
Conventional 2D cell cultures and in vivo rodent models have been used to assess the effects of drugs on tumor cell growth for many decades. However, they often fail to faithfully recapitulate the native human tissue-specific microenvironment. In the last few years, more complex in-vitro models have been developed to simulate the micro-environment of original tumors including transwell cultures, spheroids, and organoids in ECM gels. Yet, it remains challenging to design ideal materials that are flexible, biocompatible and capable to be applied for high-throughput assessment and screening.
Novel multifunctional polymers and injectable hydrogel systems were prepared via controlled living polymerization and conjugation methods. These polymers can rapidly form stable hydrogels with modified bio-macromolecules via chemical or photo-cross-linking approaches. Two-photon high-resolution 3D printing and microfabrication techniques were utilized to construct controllable micro-patterns within the hydrogels. Dynamic interactions between tumor cells and material microenvironments can be observed by using a long-time live imaging system.
Aim to understand the biological mechanism of cell-cell and cell-ECM interactions during cancer progression, and to develop advanced in-vitro 3D tumor model for cancer research and drug screening.
