Putting a Face to XIAP
After more than 15 years studying the XIAP gene, Colin Duckett, PhD, a professor of Pathology and Internal Medicine at University of Michigan, had the opportunity to meet a pint-sized patient who personified his years of cellular research.
“It’s very different when you have the chance to put a face to something you’ve been studying for years. I left the room after I met Aiden and I was completely humbled,” he said. “We co-discovered the XIAP gene in 1995, and although it has been the focus of my lab’s research for more than a decade, it was a moving experience to actually meet somebody whose illness is caused by a mutation in that gene.”
In the early 1990s, Duckett discovered XIAP, the first of a family of genes known as Inhibitors of Apoptosis, or IAPs.
IAPs play a number of different roles in the cell, but one of their major roles is to inhibit a process of cell suicide, called apoptosis, or programmed cell death. The normal, healthy cell death process is disturbed in a variety of diseases such as cancer and neurodegenerative disorders. Besides contributing to the control of cell death, XIAP has a number of other, some less defined, roles in the body. In recent years scientists have identified that mutations in the XIAP gene are the culprit behind X-linked lymphoproliferative disease type 2 (XLP-type 2), in which children experience severe limitations in the ability of their immune system to respond appropriately to common viral infections and are at risk for an overwhelming inflammatory response and colitis.
Duckett leads a research lab at the University of Michigan that investigates the role of XIAP in both healthy and diseased settings. Working side-by-side with pediatric specialists who treat children like Aiden, who was diagnosed with XLP-type 2 at less than one year of age, Dr. Duckett and his colleagues at U-M C.S. Mott Children’s Hospital are beginning to identify revealing trends that shed light on the various disorders like Aiden’s.
Duckett says that this multi-disciplinary approach in which lab scientists work in partnership with their colleagues who are working with children like Aiden in the clinic each and every day, is what makes Michigan such a unique place for families to receive care.
“There are renowned experts at all the different levels of the program here,” Duckett says. “Having been at Michigan for 12 years, I’ve always been struck by the incredible resources we are able to assemble to team up against these diseases. It’s the most rewarding scientific experience to be able to put all these things together and really make a difference for these children.”
Duckett said he is happy to see a capable team take his initial discovery into new areas of work.
“There are so many levels of expertise in the University of Michigan Health System and the Medical School, what we’re doing with XIAP research is just one small component of what’s happening all over campus” he said. “The focus across the board is on learning more and using it to changing the way children with diseases, like XLP-type 2, are treated and, we hope, ultimately cured.”