Research | Lamlab

Research focus

Calcium Regulation

Intracellular calcium regulation is essential to maintain normal contractile function of cardiac cells. Calcium dysregulation have been shown to be a hallmark in various types of cardiac diseases. While the importance of calcium in cardiac function has been appreciated for very long time, we still lack the understanding on how calcium is precisely regulated under various physiological conditions. This prevents us from developing proper strategy to correct the fundamental issue. With proteomic and genomic approaches, my lab is interested in identifying new regulators for calcium control and examining the shift of function in different diseased conditions.

signal crosstalk

Given the central role of calcium in regulating various cellular responses, it is important to understand how cardiac cells regulate local calcium signaling to activate signaling in the milieu without affecting other processes. Moreover, we previously identified that chaperone network can couple SR calcium signaling with ER stress signaling response. Disruption of this crosstalk is capable to sensitizing cardiac cell to cell death. Thus, one major research direction in my lab is to identify and understand novel crosstalk, which allows us to gauge the feasibility to simultaneously target two diseased mechanisms in failing hearts.

Cardio-oncology

Cardiotoxicity, such as reduced cardiac function and induction of arrhythmia, is a major cause for drug withdrawal in the market. Furthermore, the application of promising treatment can be limited by black box warning with adverse cardiovascular complication. Classic examples are anthracycline and tyrosine kinase inhibitors, which are commonly used in cancer therapy. My lab is interested in identifying the cardiac-specific mechanisms induced by those agents. It will allow us to develop strategy to prevent the adverse side effects in the heart but retain the cancer killing property.

how do we do it?

Cell-based platform

The advent of induced pluripotent stem cells (iPSCs) allows us to study disease using patient genetics. iPSCs are self-renewal and proliferative, which provides us unlimited source of cells. In our lab, we simply derive our desired cell types from iPSCs to study disease mechanism and test drugs.

Tissue-to-organ-to-physiology

To verify the findings from cell-based platform, we employ two different approaches. First, we use engineered heart tissues generated from iPSC cell derivatives, which possess human genetic materials. Second, we employ rodent models (mouse and rat), which has well-defined cardiac physiology. Combining all approaches, we can study disease and test drug from 2D cell platform, to 3D tissue model, to living animal level.

Mouse echocardiogram

Beating human iPSC cardiomyocytes