Research in Action: NIH Grant Enables Cavener Lab to Discover Mechanisms to Improve Insulin Regulation

A typical day for Doug Cavener, the new Dean of the Eberly College of Science, is anything but typical. While he spends most of his week attending to administration and fundraising duties for the college, one may also find him sitting at a microscope looking at fluorescent pancreatic beta cells with one of his graduate students or analyzing giraffe genome sequences at his computer. That’s because in addition to his administrative responsibilities, Cavener runs a research lab focused on the developmental and physiological regulatory processes that are important in the regulation of metabolic and neurological diseases. He also leads a team made up of scientists here in the United States and in Africa that is working to sequence the giraffe genome in order to better understand the genetic basis of the giraffe’s unique morphology and cardiovascular system.

This month, the Cavener lab received a four-year, $1.3 million grant from the National Institutes of Health to study insulin regulation. Maintaining a narrow range of circulating insulin is critical to ensuring normal blood glucose levels and preventing the onset of diabetes and its plethora of negative downstream effects on human health. “The regulation of insulin has been intensely studied since its discovery in 1921, but the molecular and cellular mechanisms that integrate insulin synthesis, quality control, trafficking, and secretion are poorly understood. The goal of our work is to understand these mechanisms and apply them to the treatment of diabetes,” said Cavener. Barbara McGrath, senior research associate in the Cavener lab, added “This new award from the NIH not only provides us funding to keep our momentum going, but it also signals to us that many of our peer researchers share our enthusiasm. That is enormously gratifying!”

Cavener and McGrath, along with postdoctoral researchers and graduate and undergraduate students, have been studying the function of the protein PERK, an eIF2α kinase, since its discovery in 2001. PERK is among a small number of genes that is so important for pancreatic beta cell function that its absence results in permanent neonatal diabetes in humans and mice. Permanent neonatal diabetes appears within the first six months of life for humans and persists throughout the lifespan due to the body’s inability to make enough insulin. Studies from the Cavener lab over the last few years have implicated PERK as a critical coordinator of insulin folding, quality and quantity control, trafficking, and secretion. This newly awarded grant from the NIH will allow Cavener’s team to reveal the mechanisms by which this important regulation is achieved and then apply these discoveries to the treatment diabetes.