Pharmacy, Natural & Health Sciences

From DNA to Zebrafish

Expanding Manchester’s Pharmacogenomic Research

Image of Joseph Chambers with Zebrafish in ManchesteRx Magazine
Joseph Chambers transports adult zebrafish pairs in tanks to a lab for observation at Notre Dame.

You might say his work is about a very small fish in an ocean of research possibility. Meet Joseph Chambers, Ph.D., an assistant professor of pharmaceutical sciences & pharmacogenomics who is most frequently asked, ‘but why do we care so much about fish?’

Chambers joined Manchester Pharmacy in July 2020 after completing his graduate degree in cell and molecular biology at the University of Notre Dame. His research there, to be more specific, was focused on molecular biology and genetics using zebrafish to understand and find improved therapies to treat kidney diseases.

“My work involved knocking out a gene or altering its expression, and applying chemical treatments, to see downstream genetic or molecular effects that might occur,” Chambers said.

Often used in teaching genetics, zebrafish share around 70 percent of human genes. Chambers notes that as much as 84 percent of human disease-causing genes have a functional equivalent in zebrafish. Through his research program at Manchester, he aims to match zebrafish and human pharmacogene homologs. In other words, he will find and map exactly which zebrafish genes have a common ancestral DNA sequence to humans – perhaps becoming the first to do so.

Chambers sees zebrafish as a perfect fit for Manchester’s graduate programs in pharmacogenomics, allowing graduate students to gather much more data in only a year than would be possible in mouse models. Chambers also sees an opportunity to integrate zebrafish into his teaching curriculum, including collaborating with undergraduate faculty at the North Manchester campus.

Comparing the size of a mature zebrafish to your pinky finger, Chambers explains how zebrafish transparent embryos develop in egg like chorions outside of the mother, making organ development easy to observe. Their major organs, tissues and blood have features that are comparable to human systems. Zebrafish also can regenerate organs, including heart, kidney, spinal cord, retinas and fins.

“Organs, such as the kidneys and eyes develop in days and the fish is fully mature in three months, which allows for noninvasive evaluation of organ development, malfunction and toxicity,” Chambers said.

Once zebrafish-human gene pairs are established, researchers can quickly identify which genes have the highest degree of similarity, Chambers said. These top-candidate genes will be selected for the next research phase; investigating molecular mechanisms that will open pathways to development of improved patient therapies. He sees a potential for expanding pharmacogenomic research at Manchester that’s adaptable to many different systems or diseases.

Each person’s unique genetic composition determines a drug response which affects the drug’s safety and efficacy in that patient. In his research abstract, Chambers notes that according to the U.S. Food and Drug Administration’s Adverse Events Reporting System, the occurrence of adverse drug effects has tripled over the last decade. Through his homologous identification, Chambers sees zebrafish as the most expedient way to address adverse drug responses, key to advancing the field of pharmacogenomics.

His broader research goal is to ultimately provide zebrafish models and matched genetic data as a resource for other research programs at Manchester.

“The really big picture is to position Manchester to lead in establishing basic and translatable research here in Fort Wayne,” Chambers said.

That sounds like a pretty big role for tiny fish.