Molecular Biology, Developmental Biology, Toxicology, Parasite Metabolism, Cell Biology

General Lab Info:

The Holowiecki lab uses the zebrafish (Danio rerio) as a model organism to study molecular toxicology and developmental biology. Owing to their small size and rapid transparent development, zebrafish embryos can be utilized for experiments that are not feasible in traditional mammalian models. Furthermore, due to the high degree of evolutionary conservation between vertebrate’s, data obtained using zebrafish have direct relevance to human health.

Specific Interests:

Cardiovascular Development-Origins of congenital heart defects

Congenital heart defects (CHDs) are the most common congenital malformation occurring in about 1 in 100 births. Of these defects, roughly 30% are related to the cardiac outflow tract (OFT). However, our current understanding of the mechanisms underlying most congenital OFT defects is rather limited. In this regard, determining factors involved in regulating OFT development will significantly enhance our ability to detect, prevent, and treat CHDs in children.

Cellular Stress– Understanding mechanisms which confer protection against oxidative stress.

Reactive oxygen species (ROS) are harmful byproducts of normal aerobic respiration. Protection against these harmful molecules is conferred  by antioxidants which essentially “quench” ROS. “Oxidative stress”, which drains cellular energy and destroys our cells, occurs when there is an imbalance between harmful ROS and protective antioxidants. To this end, oxidative stress is associated with several diseases associated with the kidney, skin, eye, heart, lungs, joints, brain, and digestive system. Thus, developing a better understanding of how antioxidants are maintained will provide novel insights regarding the mechanisms in which our cells cope with oxidative stress.

Specific Projects:

Using a Combined Chemical and Molecular Approach to Study Organ Development in Zebrafish (Danio rerio)

Bilirubin (BR) is a potent antioxidant which is generated enzymatically by the evolutionarily conserved heme degradation pathway. While the genes involved in this pathway are primarily known for their roles in degrading toxic heme, other roles have been suggested based on their specific expression patterns (eye, liver, heart). In this regard, our lab uses the zebrafish (Danio rerio) as a model organism to study the developmental expression patterns of these heme degrading genes under normal and stressed conditions to further understand their potential developmental roles.

 

Determination of the Functional Characteristics of Zebrafish Biliverdin Reductase Isoforms

Oxidative stress results from an overabundance of reactive oxygen species (ROS) which harm cells in multiple ways and can lead to tissue/organ damage. Protection against harmful ROS is conferred via antioxidants such as bilirubin (BR) which is generated enzymatically through the action of biliverdin reductase. Interestingly, while BR serves as a potent antioxidant, too much is toxic and is harmful to our cells. To this end, our lab uses the zebrafish (Danio rerio) as a model organism to study the complex mechanisms that regulate BR metabolism to ensure a healthy cellular environment.