Physical properties of the microenvironment (e.g. mechanical and transport considerations) are critically important to tumor induction and progression, and mediate the establishment of metastases at preferential target sites. We explore multidisciplinary strategies including tissue-engineered and microfabricated model systems, biomaterials, and advanced imaging approaches to define the multiscale mechanisms by which the physical microenvironment regulates cancer. In particular, we apply this toolbox to better understand obesity-associated breast cancer, bone metastasis, and cancer metabolism with the ultimate goal of identifying new therapeutic targets to improve the prognosis of cancer patients.
Biophysical regulation of obesity-associated breast cancer
Obesity introduces changes to adipose tissue that increase the incidence and mortality for many cancers, but the underlying mechanisms are less clear. We study how obesity influences the biophysical properties of adipose tissue and determine their functional consequences on breast cancer. We are particularly interested in how adipocytes, adipose stromal cells, macrophages, and interstitial extracellular matrix regulate tumor cell migration and chemoresistance as a function of varied mechanosignaling. We explore these links by combining engineered tumor models—including microfluidic devices, tumor spheroids, and collagen hydrogels—with molecular biology and advanced imaging techniques, in vivo tumor models, and patient-derived tissues from our clinical collaborators at Weill Cornell Medicine.
Bone material properties as regulators of skeletal metastasis
The skeleton is a primary site for metastasis, but how the unique material properties of bone regulate the underlying cellular and molecular mechanisms is poorly understood. Bone ECM is a composite material largely consisting of bone mineral nanocrystals embedded within a collagen type I-rich organic matrix. Interactions between both components determine the mechanical and chemical properties of the skeleton with potentially important implications for the behavior of both tumor and bone-resident cells. By combining tissue engineering approaches with biofunctional bone matrix models, we investigate how the organic and inorganic components of bone matrix and changes thereof influence the phenotype of tumor and bone-resident cells and how these changes regulate early and late stages of bone metastasis.
Linking tumor cell metabolism with the physical microenvironment
Aberrant cellular metabolism is a hallmark of cancer that provides cancer cells the energy to rapidly proliferate, disseminate, and evade immune responses. However, therapies focused on interfering with tumor cell metabolism are often challenged by the fact that tumor cells can readily adjust their metabolic phenotype depending on the specific properties of their surrounding microenvironment. We apply multidisciplinary approaches including engineered model systems, advanced imaging modalities, and multi-omic data integration to better understand how reciprocal interactions between tumor cells and their physical microenvironment regulate cancer cell metabolic phenotypes and which role these changes play in tumor progression and metastasis.