Research

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:

 

High-Throughput Microscale Tissue Engineering

Cellular microarrays:

Our laboratory utilizes high-throughput cellular microarrays to examine the effect of combinatorial microenvironmental signals on the differentiation and function of stem and progenitor cells.

3D fabrication and analysis:

We develop methods that enhance the capability to analyze cellular responses within defined 3D biomaterial environments, including approaches for increased multiplexing.

 

Liver Development and Disease

Role of the microenvironment in liver tumorigenesis:

The dynamic nature of liver development has limited the understanding of the role of the microenvironment in hepatoblastoma, a pediatric liver cancer.  We aim to explore the influence of extracellular matrix and cell-cell interactions on hepatoblastoma differentiation stage and gene expression signatures, which have been associated with tumor aggressiveness and clinical outcome.

Bile duct morphogenesis and associated developmental disorders:

The majority of congenital liver diseases are due to defects in bile ducts.  We are utilizing both engineered 2D cellular arrays and 3D biomaterial systems to explore the biliary differentiation of liver progenitors and bile duct formation. 

Bidirectional liver-blood cellular interactions:

Within the developing fetal liver, interactions between liver and blood lineage cells coordinately regulate hematopoiesis and the differentiation of liver progenitor cells.  We aim to develop engineered model systems to investigate these critical cell-cell interactions, which have been previously difficult to address with standard culture methods or current in vivo approaches.       

 

We gratefully acknowledge the following funding sources: