Overview of Science and Mission
Basic Science
What is Basic Science Research and how does it help the ERC?
Basic Science...
- allows our team to investigate the mechanisms of cell death in a pure cardiomyocyte culture;
- allows our team to specifically assess how cardiac cells respond to ischemia- reperfusion (I/R) injury; and
- allows us to test new methods to prevent this injury.
Once we know how and why the cells are dying, we can manipulate the responsible molecules and pathways in hopes of preventing cell death.
Why are the "first few minutes critical"? For cells, it is a question of living or dying...
Our research has shown the first few minutes of reperfusion are critical to determining whether or not cardiac cells will survive an ischemic injury. During these first few minutes, when the cells are reintroduced to oxygen, the cell makes a decision to live or to die. This decision is impacted by both the generation of reactive oxygen species and the activation (or inactivation) of signaling kinases during reperfusion.
What does our team of researchers work on?
Using state-of-the-art molecular biology techniques, genomic analysis, and online cell imaging, our team works to elucidate the mechanisms behind I/R-induced cell injury by studying and examining:
- The intricate pathways involved in reperfusion and ischemia
- Apoptosis (a type of programmed cell death)
- Free radical injury following ischemia
- Akt signaling
- p53-regulated signaling
- Finding ways to protect cardiomyocytes from cell death following an ischemic episode
- Examining the benefits of hypothermia
- Examining the use of herbal compounds in protecting cardiomyocytes from cell death
Apoptosis (Programmed Cell Death)
We have shown that:
- apoptosis plays a key role in I/R-induced cardiomyocyte cell death.
- apoptotic cascade begins immediately upon reperfusion, with the events of ischemia setting the stage for the ensuing cell death.
- blocking this pathway using specific inhibitors abrogates much of the reperfusion injury..
Free Radical Injury Following Ischemia
Free radicals such as superoxide and hydroxyl radical play an important role in many biological processes, including intracellular signaling. However, because these species are so highly reactive, they also play a role in causing cell damage. We have shown that:
- a burst of reactive oxygen species is generated immediately upon reperfusion (especially superoxide and hydrogen peroxide).
- this burst is associated with cardiomyocyte damage, decreased cell contractions, initiation of the apoptotic cascade, and cell death; blocking this burst protects cells against I/R injury.
p53 Signaling
Not just associated with cancer anymore!
While p53 is a protein typically associated with cancer, it may play a critical role in the regulation of cell death and metabolism in a number of diseases, including ischemic heart diseases. We have shown that:
- p53 is activated by events of ischemia and may have multiple roles in regulating proteins involved in apoptosis and
- p53regulates certain other proteins, which may have critical metabolic roles in determining the response of a cell to stresses that occur during ischemia and reperfusion.
We are currently investigating how p53 can be manipulated to help protect cardiac cells from these stresses.
Therapeutic Hypothermia
Therapeutic hypothermia, or cooling cells to below the optimal temperature for normal metabolism, has been shown to be protective in a few cases of ischemic disease, such as stroke. Current studies focus on:
- Understanding the molecular pathways involved in hypothermia protection on a cellular level
- Hypothermia being protective in our cardiomyocyte model of I/R – hypothermia decreases the generation of free radicals and reverses many of the damaging pathways involved in this ischemic injury.
We continue to explore the intracellular mechanisms that afford this protection in hopes of developing an alternate treatment to mimic hypothermia and its protective effects.
Herbal Preconditioning
The fight against sudden death requires innovative thinking. Innovative thinking requires innovative researchers "thinking outside the box". Our herbal preconditioning researchers, with decades of experience, are:
- Investigating the possible role of herbal medicines in preserving cell function
- Studying the effect of two common herbs on cardiomyocyte cell death
- Examining the ability of baicalein to precondition cardiomyocytes
- Looking at the ability of grape seed extract to act as a post-conditioning agent
