Our work is focused on building advanced in vitro models of human pathology. We use state-of-the-art micro- and nanotechnology to control biological components at the length scale that is relevant to physiology and pathology. The goal is to elucidate fundamental mechanisms of disease, improve disease diagnosis, and develop new therapies.
Sickle Cell Disease
Sickle cell disease is a devastating genetic disorder that affects more than 13 million people worldwide and results in chronic pain and fatigue, frequent hospitalization, and high mortality, especially among children. A major focus of our group is to understand the mechanisms of vaso-occlusion, the primary pathological mechanism in sickle cell disease. My laboratory has developed a range of tools and methods to facilitate these studies, including physiologically sized microfluidic channels, tools to regulate blood pressure, methods to finely control blood oxygen, and methods to monitor blood flow in real time. Ultimately, our goals are to understand how vaso-occlusion proceeds in vivo and under which conditions vaso-occlusions are most likely to occur. Additionally, we anticipate that we may be able to predict which patients are most at risk for vaso-occlusive crises, and we believe the knowledge and tools developed during this work will enable the discovery and development of new therapies for this terrible disease.
Metastases are responsible for ~90% of human cancer-related deaths, but our understanding of the stages of metastasis and the mechanisms that drive metastatic spread is sorely lacking. A major challenge in elucidating metastatic mechanisms is the lack of a model system that permits direct visualization of the metastatic process, especially the later stages of extravasation and colonization of the metastatic site. We are developing a novel microfluidic platform and assay for metastasis that will enable detailed mechanistic studies of the metastatic process. The ability to directly visualize key steps in the metastatic process would lead to identification of key features of tumor cells and understanding of the metastatic niche that could be specifically targeted to limit metastatic spread. The model system we have developed permits dynamic temporal analysis within a physiologically relevant context that is unavailable in most in vitro systems. Additionally, we anticipate that this platform will provide a more relevant model to test potential metastasis-blocking therapies.
3D Tissue Culture
Drug discovery relies heavily on in vitro models to identify, develop and test drugs before beginning clinical trials. This workfow is predicated on the idea that the behaviors seen in in vitro models will be good predictors of performance in clinical trials, but this is often not the case. Poor representation of human organs and disease states often leads to failure of drugs during late-stage clinical trials, significantly increasing the time and cost required to bring new therapies to market. Similarly, animal models often do not accurately represent human responses, are costly, and are not amenable to high throughput studies. To overcome these challenges, our group is actively developing a high throughput 3D tissue culture platform based on microfluidic droplet technology. The idea is that microscale tissue constructs can be rapidly generated, and these microtissues can incorporate a high degree of biological complexity including mutliple extracellular matrix and cellular components. Moreover, our group is working to demonstrate that complex cellular functions such as migration, matrix compaction and reorganization, and drug metabolism can be rapidly assayed in this platform. The result will be a more in vivo-like platform for testing drugs and discovering new biological mechanisms.