CURF Introduction: Studying Rare Metabolic Disorder in Novel Mouse Model

My name is Eric Gliniak, and I am a Junior studying molecular biology. I am a recepient of the Chancelleras Undergraduate Research Fellowship. I am very greatful for this opportunity and excited for the work ahead. My application for this award was focused on my work in the Palladino lab. I have been at Dr. Palladino’s lab since the fall of my freshman year, I started as a work-study student and gradually made my way into a research position. My plans after graduating from Pitt is to attend graduate school to evenutally earn my Phd in molecular biology. My ultimate goal is to begin working in industry perferbally in the biotech sector.

Palladino Labs studies a metabolic disorder called Triosephosphate isomerase (TPI) deficiency. TPI is one of the enzymes participating within the glycosidic pathway. Due to a mutation at the TPI locus, which is usually a missense mutation, the body produces a mutated form of the TPI protein. This protein is functional but unfortunately degraded by the ubiquitin pathway. Due to the significant loss of TPI activity the glycosidic pathway becomes disrupted producing several characteristic symptoms. These Include hemolytic anemia, progressive neurological degradation, muscle weakness, and breathing problems. No effective treatment has been developed to aid those affected by this disorder. The aim of Palladino Labs is to characterize the disorder and develop a therapeutic pharmacological treatment.  

Recently, in collaboration with the Homanics lab a new mouse model mimicking the pathology of TPI deficiency was developed. This mouse model has shown to mimic the four major characteristics of TPI deficiency. This includes hemolytic anemia, neurological dysfunction, progressive muscle degeneration, and a reduced lifespan. due to the newness of this mouse model further characterization of it is necessary. More specifically, we want to determine how the body/tissues are affected by this disease. Through general observation we have already noticed that the spleen and intestines of our experimental mice are significantly abnormal. This is a novel observation and could giver further incite into the pathology of the disease.

This project is incredibly exciting because it opens up a lot of new avenues for our lab. The characterization of this novel mouse model will help us in conducting a drug study to hopefully find a pharmacological therapy for this disease. The lab obtained a list of possible therapeutic compounds which were put through an optical drug screening assay. This process could eventually lead to therapeutic treatment for TPI Deficiency and help out those who suffer from this disease. I would like to thank my research mentors Dr. Palladino, Dr. Kaufmann and Tracey Myers.

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