Sharon Wang

Heart disease and stroke statistics has shown that cardiac valve diseases are among the top killers in adults and induced 99,000 inpatient valve procedures in United Sates in 2004. So far, heart valve replacement is the most effective treatment for late-stage valvular diseases. But due to the lack of human valve supply, most patients ended up with valves from pig or mechanical valves, both of which can trigger unwanted immune resistance and damage to the local blood vessels. Valve tissue engineering, with the promise of regenerating a functional valve based on the healthy cells from the patients, has since emerged as a novel method to solve the above problem. The idea is to culture the valvular interstitial cells (VICs), one of the main cell types in human valves, within special-designed matrix and implant the regenerated cell population to the injured site for tissue reconstruction. The VICs were selected because they can be activated to proliferate and remodel the extracellular matrix (ECM) during endogenous tissue repair. When the tissue has restored, activated VICs go back to quiescence or undergo programmed cell death (apoptosis). Continuous activation of VICs leads to excessive accumulation of ECM and cells, which eventually causes tissue failure. Therefore, it is crucial that VICs be activated within a time window. My research is looking for the factors or mechanisms that control programmed cell death in the activated VICs with the hope that I can design matrix to direct cell fate. Based on literature search, I generated a list of factors regulating apoptosis in similar cell types. Then, the effect of these factors on both transcription and translation of the apoptosis-related genes in VICs will be examined. With the confirmed factor(s) mediating apoptosis process, I can design matrix conjugated with the factor(s) or capable of releasing the factor(s) upon certain stimulus to externally and temporarily regulate apoptosis of VICs.