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UCSC associate professor Jeremy Sanford. Photo by Calyse Tobias
UCSC associate professor Jeremy Sanford. Photo by Calyse Tobias.

Jeremy Sanford, associate professor of molecular, cellular and developmental (MCD) biology, came from his home in Indiana to UC Santa Cruz in 2008 because of its esteemed reputation for housing leaders in his field. Eight years later, he started the Sanford Lab which concentrates on researching RNA proteins, and currently is making strides in understanding, and hopefully eliminating, leukemia.

The research lab specializes in cross-linking immunoprecipitation-sequencing, or CLIP-seq, which allows proteins to be cross-linked to RNAs.

On March 14, the Sanford lab, in partnership with researchers at UCLA, published a study about the role of an RNA protein, named IGF2BP3 (insulin-like growth factor 2 mRNA binding protein 3), had in the proliferation of B cells in B-cell acute lymphoblastic leukemia, referred to in the medical world as B-ALL.

Acute lymphoblastic leukemia, is a fast-spreading breed of cancer and is the most prevalent type of leukemia in children and young adults, affecting close to 200,000 U.S. patients a year. B-ALL, is a type of this leukemia, which develops in the infection fighting cells lymphoblasts, which protect the body from invading bacteria, viruses, and fungi by attaching antibodies to germs in order to destroy them.

“[CLIP-seq] allows us to cross-link proteins to RNAs they interact with in the cell using UV radiation,” said Jonathan Howard, a member of Sanford’s team who obtained his doctorate degree in MCD biology from UCSC in fall 2015. He used the analogy of catching fish (RNA) with bait (protein).

“The hook is the cross-link, and the antibody is the fishing rod,” he said.

The process allows for the identification of the protein, and then an examination of the consequences of how it interacts within the cell.

“Understanding the molecular functions IGF2BP3 provides us with the foundation for therapeutic avenues to block the binding of IGF2BP3 to its target RNA or inhibit its RNA-binding function,” Howard said. “These types of therapies could not only work in leukemia, but possibly in many other types of cancers.”

Sanford stands next to a microscope displaying cells in a petri dish. Photo by Calyse Tobias
Sanford stands next to a microscope displaying cells in a petri dish. Photo by Calyse Tobias

Prior to working on this study, the Sanford lab was researching the role of the same protein in pancreatic cancers. It then joined forces with Dr. Dinesh Rao at UCLA, who was studying the RNA-binding proteins involved in an aggressive form of B-ALL.

“It’s a perfect collaboration because [Rao] brings the disease, the clinic and the pathology to the project and we bring the molecular biology and genomics to the equation,” Sanford said.

Tim Sterne-Weiler, another researcher who worked with Howard, received his doctorate degree in bioinformatics from UCSC. Sterne-Weiler used a scientific software he built to analyze and explore the data generated by Howard.

“The research represents a substantial step toward our understanding of how the expression of an RNA-binding protein, IGF2BP3, can promote leukemogenesis [the development or progression of leukemia],” Sterne-Weiler said.

The study was published in the Journal of Clinical Investigation, a peer-reviewed journal of biomedical research published by the American Society for Clinical Investigation (ASCI), but the Sanford lab will continue researching the function of IGF2BP3.

“We feel pretty good in the idea that [IGF2BP3] is going to be a patho protein, so the next question is what is it really doing and then can you interfere with that,” Jeremy Sanford said. “IGF2BP3 — I hope — is going to be an important part of our future research.”