CANCER CELL INVASION OF THE TISSUE MICROENVIRONMENT
Cancer cell invasion of the tumor microenvironment is the first step in metastasis. We are studying the mechanics of cancer cell migration at the border of the tumor with adjacent stromal tissue, relating cell movement and optical indices to aspects of the local mechanical and molecular microenvironment.
One exciting aspect of this project is an effort to determine optical indices of cancer invasiveness using a quantitative phase imaging technique called digital holographic microscopy (DHM). This technique holds great promise for evaluation of cell-based assays and biopsy sections and produces data that are compatible with machine learning approaches to phenotypic profiling and drug screening. Results have been published in the journal Cytometry A and Biomedical Optics Express.
This project was funded by an R03 grant from the NIBIB, “A dual-modality quantitative phase and polarized light microscope to assess cell motility and extracellular matrix remodeling during invasion.”
ORAL-MUCOSA-ON-A-CHIP
In collaboration with the integrated Biomicrofluidics Laboratory (iBMF) at CUA (PI: Xiaolong Luo, PhD), we developed the first oral-mucosa-on-a-chip optimized to study mucosal toxicity response and microbiome interactions. Results were published in Biomicrofluidics and Biomedical Microdevices. In work funded by the NIDCR, this oral mucosa chip model was adapted to long-term (3 weeks) in vitro culture to create a model of mucositis initiation and damage and repair following exposure to cancer treatments. Inflammatory cytokines were screened during damage, repair, and with chip exposure to a drug known to protect the mucosa. Both engineering and molecular aspects of this research are ongoing.
BIOPRINTING AND LIGHT MICROSCOPY
In several projects, we are measuring quantitative optical parameters derived from optical signals native to living tissue, as a non-invasive, non-destructive way to understand microstructures of bioprinted and engineered tissues undergoing active remodeling. Results have been published in the Journal of Biomedical Optics, Biofabrication, Biomacromolecules, and elsewhere.
This project was funded by an R03 grant from the NIBIB, “A dual-modality quantitative phase and polarized light microscope to assess cell motility and extracellular matrix remodeling during invasion.”
FACILITIES
-BSL2 cell and tissue culture facility (Pangborn Hall Room 118)
-an optical table for optical design prototyping.
-a microfluidic chip foundry (Pangborn Hall, through collaborator Xiaolong Luo)
-optical prototyping facility (Pangborn Hall, through collaborator George Nehmetallah)
-machine shop including 3-D metal printer (College of Engineering, Computing and Physics resource)
-rapid prototyping (3-D printing) facility (College of Engineering, Computing and Physics resource)
EQUIPMENT (selected items)
-TMV4 light-based bioprinter on a microscope (Tissue Machina)
-LS820 Lumascope Incubated Microscope (Etaluma)
-8-channel peristaltic pump (Darwin Microfluidics)
-MT9950 quantitative polarized light microscope (Meiji)
-two-channel digital holographic and polarized light microscope (custom-built)
-on-stage tissue culture incubator (ibidi)
-laser speckle reflectance microscope (custom-built)