Overview of Science and Mission

Translational Science

“Bench to Beside” or “Mouse to Man” Medicine

Translational science is often referred to as “bench to beside” or “mouse to man” medicine. But, what does that mean? In practical terms, it means that lessons and observations made in basic science (“the bench”) are used in the clinical setting (“the bedside”) to aid in improving the effectiveness of current treatments and to develop new treatments for human diseases. However, in a translational research lab, clinical observations also help guide biomedical research.

Developing Models: Applying the "Bench to Bedside" and "Mouse to Man"

We have developed animal models* that demonstrate the early cardiovascular collapse seen in patients after resuscitation.
These models were generated to reflect clinical observations that the early post-resuscitation phase is critical to survival and to allow us to verify, in a whole animal system, many of the findings from our cellular cardiomyocyte model of ischemia/reperfusion.

Pathways and Markers

Our hope is that we will discover common pathways and markers associated with the reperfusion injury in both our cellular and animal models of resuscitation and we will be able to propose, investigate, and design better treatment modalities.

We use our models of cardiac arrest and hemorrhagic shock to examine molecular biomarkers such as nitric oxide, cytokines, and inflammatory proteins.
We also have funded research to study the role of p53, apoptosis, and signaling cascades during cardiac arrest and hemorrhagic shock.
We have funded projects and collaborations to assess both the genomic profile and the effect of therapeutic hypothermia in these models of resuscitation.

More About Current Research...

Apoptosis

Programmed cell death (PCD) is an important contributor to injury of myocardium resulting from loss of blood flow (ischemia) and re-introduction of oxygen (reperfusion) during and after cardiac arrest or myocardial infarction. One prominent type of PCD is apoptosis, a physiological form of cell “suicide.” Apoptosis involves many different proteins that regulate and carry out this cellular process. Normally, apoptosis functions to regulate development of many tissues and also to dispose of damaged or dangerous cells in developing and adult organisms. However, cellular stresses, such as the lack of oxygen and the over-production of oxygen radicals when oxygen is returned to the tissues, can also induce apoptosis. Our laboratories study many of these radicals, their sources, and how they affect the proteins involved in carrying out the apoptotic death of cardiomyocytes. These insights may lead to better ways to prevent cell death, particularly during and after resuscitation or reperfusion.

Signaling Cascades

Cellular responses to stresses are initiated and modulated by signaling cascades within the cell. These cascades consist of many proteins, such as the kinase Akt, which, when activated by stress, regulate other “downstream” proteins.

These signaling proteins are regulated by two mechanisms.

First, molecular alterations such as phosphorylation of specific portions of the proteins can lead to either activation or inactivation.
Second, changes in their expression levels can regulate their activity. Regulation of the expression levels of proteins is controlled in large part by transcription factors, such as the protein p53.

Many of our current translational studies involve studying cells and animals which express abnormally high or low levels of these proteins. In fact, both Akt and p53 seem to play important roles in cellular responses to oxidative stress, particularly as it relates to cell function and death. Thus, studies in cells and animals can tell us much about the importance of individual proteins in responses to stresses like ischemia/reperfusion and may yield novel approaches to preventing cardiac dysfunction under such conditions.

Genomics

Genomics is a field of scientific research that aims to characterize the structure and function of genes (and changes in their expression). We use genomics as a powerful screening tool to gain insight into the molecular pathways involved in the stress response associated with cardiac arrest and hemorrhagic shock. Using our mouse models, we are able to examine the stress response in multiple critical target organs to determine if there is a common pathway involved in the whole-body injury following resuscitation. Discovering these new targets may lead to new treatments that will improve survival.

Therapeutic Hypothermia

Therapeutic hypothermia is one of the most recent advances in the treatment of cardiac arrest, such that it was recently recommended by the American Heart Association as the only proven therapy for comatose cardiac arrest survivors. Since several landmark clinical studies demonstrated the importance of therapeutic hypothermia, we developed mouse models of hypothermia protection. ERC scientists are currently working with these models to better understand the mechanism of hypothermia protection in cardiac arrest and hemorrhagic shock.

*All of our research protocols conform to federal and University of Chicago guidelines regarding animal care and usage. For more information regarding University of Chicago guidelines, please visit our Institutional Animal Care and Use Committee website (http://ors.bsd.uchicago.edu/IACUC/).