Our research efforts are focused on understanding how microenvironmental interactions regulate cell fate decisions and the organization of tissues during embryonic development, tissue regeneration, and disease. We aim to apply fundamental discoveries in this area towards the advancement of new therapeutic approaches in regenerative medicine.

In order to study these complex processes, we utilize a tissue engineering approach positioned at the interface of several disciplines. Collectively, we aim to develop engineered tissue systems that (i) enable the controlled presentation of microenvironmental signals, (ii) facilitate high-throughput screening, and (iii) integrate with experimental disease models. Specific efforts in the lab are outlined below:

Microenvironmental Regulation of Liver Progenitor Cell Differentiation

The differentiation of multipotential liver progenitor cells is key to both liver development and liver regeneration. We are utilizing an integrated approach incorporating high-throughput cellular microarrays, synthetic hydrogel materials, and cell mechanobiology studies to deconstruct the mechanisms regulating liver progenitor cell decisions and liver functions.

Engineered Culture Models of Liver Disease

Alterations in microenvironmental signals and tissue structure are central to the initiation and progression of liver diseases, including fatty liver disease and associated liver fibrosis. We are developing in vitro culture platforms for identifying the biochemical and biophysical determinants of primary human liver cell responses in disease, that can be further used for evaluating the efficacy of novel therapeutic candidates.

Role of Extracellular Matrix in Cancer Cell Phenotype and Drug Responses

Characteristics of tumor-associated extracellular matrix (ECM) can exhibit a strong influence on tumor development, growth, metastasis, and responsiveness to therapies. Our efforts are aimed at identifying potential ECM biomarkers of drug responses, together with important mechanistic insights into how the interplay between ECM composition and intrinsic gene expression influence cell signaling and drug responsiveness in cancer.

Research Funding

The Underhill Lab gratefully acknowledges previous and current funding from the following sources: