Guiling Zhao | Mysite

Guiling Zhao PhD

Dr. Guiling Zhao’s research is focused on investigating the cellular and molecular mechanisms under which cardiovascular function is regulated by calcium, calcium related proteins and ion channels. She has discovered that type 1 IP3R (inositol trisphosphate receptor) is dominant in cerebral artery smooth muscle cells and that it regulates the vasoconstriction and dilatation, not only through calcium release from SR (sarcoplasmic reticulum), but also through crosstalk with plasma membrane ion channels (i.e. BKCa, TRPC3). Dr. Zhao also discovered that STIM1 (stromal interaction molecule 1), a calcium sensitive protein located in SR, regulates SERCA (Sarco/endoplasmic reticulum Ca2+ ATPase) activity in the steady state and the rate of SR Ca2+ leak in ventricular myocytes.

Taking advantage of her vascular biology background and being driven by her interest in cardiovascular physiology, Dr. Zhao’s current work centers on the regulation of blood flow control under microcirculation in the heart, using the unique working models and tools she has developed. She has found that ATP-sensitive K+ Channels (KATP) in cardiac myocyte drive the local blood flow through Electro-Metabolic signaling. Her ultimate goal is to make a mechanistic contribution and support in the development of new strategies to treat cardiovascular diseases.

We are interested in the cardiovascular physiology, with an emphasis on Ca2+ signaling and its regulation in heart and vasculature. Specifically, the PI and her research team have been working on the following three projects:

STIM1 in heart.

As a SR Ca2+ sensing protein, STIM1 is well known as a stimulator of store-operated Ca2+ channel (SOCC) or Ca2+ release activated Ca2+ channel (CRAC), especially in non-excitable cells. However, the role of STIM1 in heart is not well understood. Using confocal, immunochemistry, patch clamp, and viral transfection techniques, we found that STIM1 in rat ventricular myocytes is not sensitive to SR Ca2+ depletion. Instead, STIM1 overexpression causes SR Ca2+ overload and cell arrhythmia. Further study indicates that STIM1 binds to phospholamban, an endogenous SERCA regulator and thus releases and activates SERCA. See Zhao et al (2015). PNAS.

Stretch-dependent Ca2+ signaling in arterial smooth muscle.

Using the new device developed in our lab, we were able to stretch single cardiac myocytes, skeletal muscle cells, as well as arterial smooth muscle cells. And cell length, cell tension, and Ca2+ signal are able to be recorded at the same time. The combination of the state-of-the-art techniques (single cell stretch, patch clamp, Ca2+ imaging) allows us to better understand the mechanisms of how pressure (stretch)-induced vasoconstriction occurs.

Blood flow control in heart.

One key question for us to ask is how heart blood flow is controlled by cardiomyocytes? Or how does heart communicate with arterioles? With this question, we have built a new ex vivo working model which enables us to image cardiac myocytes, capillary bed and coronary arteriole in the right ventricle papillary muscle at different pressures. Combining with our state-of-the-art optical imaging system, we were able to monitor the "blood flow" ex vivo as well as to image the diameter change of capillaries and arterioles. In addition, the function of cardiac pericytes is being investigated using this ex vivo working model.

To contact Dr. Zhao send an email here: GZhao@som.umaryland.edu