Research

RESEARCH THEME

Cardiac excitation–contraction coupling is controlled by three dynamic systems: the electrical system, the Ca²⁺ signaling system, and the contractile system. Recent studies by us and many other colleagues reveal that these non-linear dynamic systems interact with one other and their interactions are fundamental to heart disease mechanisms. For example, mechanical stress during muscle contraction can disrupt Ca²⁺ signaling to generate spontaneous Ca²⁺ activities, which can affect the Na⁺/Ca²⁺ exchanger and Ca²⁺-sensitive channels etc. to disrupt electrical activities and lead to arrhythmias. Our approach is to study integrated behavior of dynamic systems in order to understand the exact mechanism of cardiac arrhythmias. Our interdisciplinary team combines experimental investigation with mathematical modeling to conduct in-depth analyses of the dynamics systems in order to better understand heart diseases mechanisms and to develop effective therapies.

RESEARCH AREAS
⇒ Cardiac Electrophysiology (more)
⇒ Ca2+ signaling system dynamics (more)
⇒ Ca2+→ electrical system interaction (more)
⇒ Mechanical analysis of cardiac myocyte contraction (more)
⇒ Mechano-chemo-transduction linking contraction → Ca2+ signaling (more)
⇒ Mathematical model of mechanical load effect on Ca2+ dynamics (…upcoming)

HEART DISEASES
Many heart diseases increase the risk of cardiac arrhythmias. We hypothesize that a common thread linking these arrhythmias is abnormal mechano-chemo-electro-transduction. Testing this hypothesis may provide a unified explanation for arrhythmias in seemingly distinct diseases and provide novel strategies for combating arrhythmias.

⇒ Hypertension induced cardiac arrhythmias and heart failure (more)
⇒ Familial Hypertrophic Cardiomyopathy (FHC, or HCM) (more)
⇒ Muscular Dystrophy Cardiomyopathy (…upcoming)

INNOVATIVE TECHNOLOGIES

Cell-in-Gel system to control mechanical stress at single cell and molecular level to study how mechanical stress feedback to modulate the Ca2+ signaling system in myocytes. Broader Impact: This innovative technique can be widely used to study mechano-chemo-transduction in various cell types. selfAP-clamp with Ca2+ cycling technique to study how Ca2+ feedbacks to affect various ionic currents how Ca2+ dysregulation causes arrhythmogenic APs. AP-clamp Sequential Dissection (‘Onion-Peeling’) to record multiple ion currents under action potential (AP) clamp in a single cell, which enables direct experimental study on how the inward versus the outward currents in the same cell counterbalance to shape the action potential. ‘Cell sausage slice’ technique to position the single myocyte upright for imaging the cell’s transverse section at high resolution. SHG-2PF multimodal imaging to study localized Ca2+ and sarcomere contraction in subcellular microdomains at high resolution.