Bone Mets Laboratory
Eleonora Dondossola, Ph.D.
Areas of Research
- Prostate Cancer
- Kidney Cancer
- Tumor Microenvironment
- Tissue Engineering
- Cancer Metastasis
The research of the Bone Mets Lab focuses on modeling and targeting the mechanisms of progression and therapy response in bone metastatic cancers, with emphasis on the role of tumor-stroma bidirectional communication.
Bone metastasis is a lethal consequence for prostate and renal cancer patients, mostly due to the emergence of resistance and therapy failure. The interaction between cancer and stromal cells has been recently identified as a key player in supporting both disease progression and treatment resistance. A major challenge in addressing this cooperation, however, is the lack of suitable model systems that exploit a bone-centric approach for testing therapeutic options. Thus, to reduce morbidity and eventually eliminate cancer, it is critical to establish biologically informed preclinical models that provide mechanistic understanding of tumor progression in bone and treatment outcomes.
Our multidisciplinary research program takes advantage of advanced tissue-engineered in vivo models, intravital multiphoton microscopy, 3D organotypic in vitro systems, and computational oncology. We aim to apply these models to identify cellular and molecular determinants of response and resistance to targeted radiotherapy, immunotherapy and kinase inhibition, and to develop novel options for treatment, with the final goal of clinical translation to improve patient survival and quality of life.
As a parallel track, we extend the use of intravital multiphoton microscopy to monitor the fibrosis elicited by biomaterial implantation (foreign body response) and its therapeutic interference in real time. We investigate the dynamic evolution of the foreign body response and the role of key mediators of the fibrotic encapsulation, including extracellular matrix, immune and non-immune stromal cells (fibroblasts, pericytes, endothelial cells).
Reconstruction of polycaprolactone electrospun scaffold (second-harmonic generation and third-harmonic generation by nonlinear multiphoton microscopy)
Intravital microscopy image of the foreign-body response to an implanted biomaterial captured at the multiphoton microscope
Bone metastasis captured at the confocal microscope
Bone metastasis captured by intravital multiphoton microscopy
Polycaprolactone scaffold seeded with human mesenchymal stem cells
Osteolytic lesion captured by intravital multiphoton microscopy over 9 days-each color represents a different time frame in the osteolytic progression
Polycaprolactone scaffolds seeded with osteoblasts and patient-derived tumor cells