My research students and I are on the quest to find a myocyte “proliferation switch.” We use zebrafish as our animal model, because they have the capacity to readily turn on muscle cell division (both skeletal and cardiac) to repair damaged tissues or damaged hearts. If we can discover a gene pathway that is switched on/off in zebrafish when they are regenerating muscle tissue—but not switched on/off in humans in response to muscle damage—we may find a potential molecular target for the treatment of cardiac and muscle tissue damage in humans. We have two ongoing projects to address our research quest.
The Molecular Response of Zebrafish Hearts to Excessive Cardiac Overload Stress
We use a “fish treadmill” to force zebrafish to swim against a strong current for very long periods of time. This creates a severe cardiac overload stress condition, overworking the heart. In response, we have established that zebrafish hearts switch on cardiomyocyte proliferation as a compensation in order to increase muscle mass to handle the cardiac overload. The larger zebrafish heart is able to very efficiently compensate for the overload stress condition. Human heart cells do not have this capacity to efficiently proliferate in response to stress. We are currently investing the expression of two particular genes that may turn out to be the “proliferation switch” that turns on cell division of zebrafish cardiomyocytes in response to excessive cardiac overload stress.
The Wound Healing Response in Adult Danio rerio
We have found that zebrafish efficiently regenerate—at the gross-examination level—all tissues that are damaged in a deep-puncture burn wound. We are currently working on classifying the normal process of tissue regeneration in zebrafish inflicted with this type of wound. Next, we seek to discover a molecular switch that turns on efficient cell division in skeletal muscle myocytes in response to this type of a wound. In addition, we seek to understand if different types of treatments can prevent infections in these types of wounds.
Humans suffer deep-puncture burn wounds on the military battlefield in the form of gunshot wounds. If these wounds become infected before medical attention can be applied, the wound can result in loss of limb or loss of function. If we can identify molecular mechanisms that control the zebrafish efficient regeneration response to this type of wound, as well as mechanisms to prevent infection, we may be able to target these molecular mechanisms as potential treatments of gunshot wounds in humans.
Experimental Methods Used in Dr. Schoffstall’s Lab
To carry out our scientific quest, we use several experimental techniques, including:
- Quantitative PCR
- Conventional PCR
- Protein gel electrophoresis
- Dot Blot Screen
- Western Blot
- Immunohistochemical staining
- Fluorescence microscopy
- Wound infection control
- Microbiological identification of wound pathogens