Researcher at the University of Michigan Hospitals
The Cure Starts Now recently sat down with Dr. Carl Koschmann to discuss his research grant for Therapeutic Reversal of Pre-natal Pontine ID1 Signaling in DIPG.
What is the purpose of your research?
“Our aim is to get sequencing from as many spots as we could separate from the pons, where the tumor is located, and, effectively, get as much information as we could about each spot, while trying to figure out how the spots were different and how we might see differences in the DNA that has mutated, as well as genes that were over-expressed or under-expressed. We call that heterogeneity within the tumor. At this time, there are very few DIPGs that have been studied in such detail, but, still, there's not a lot that we know. Additionally, we looked for a gene that was expressed called ID1 because we saw a mutation in the gene ACVR1 and the Hawkins lab (Dr. Cynthia Hawkins, Researcher at Sick Kids Hospital and member of the Medical Advisory Council of The Cure Starts Now) had just published a paper on ACVR1 and its upregulation of this gene ID1.”
How does ID1 affect DIPG tumors?
“ID1 has been found in a lot of human tumors, including breast cancer and adult glioblastoma to control invasiveness of the tumor, and DIPG is the most invasive tumor. Both our lab and the Hawkins Lab have concluded that it may be involved in DIPG. Not much information beyond that is known. We know that that ACVR1 upregulates ID1, but we don't know in human tumors is ID1 expressed differently in different spots in the tumor, is it expressed in all DIPGs, and is there a way that it can be targeted? In order to continue our quest for these answers, we've developed mouse models in our lab and our best mouse model shows the brain developing which gives us insight into the ID1 gene, and how proteins might bind that and cause it to be upregulated.”
Have the mouse models given you any indication as to why DIPGs develop?
“Our best explanation is that when a child’s brainstem develops, which mostly happens prenatally, those cells use ID1 to form a brainstem. Once the brainstem is formed, that signal pathway is turned off because the brainstem doesn't need to keep growing. It's formed by age four to 10 at the latest. What we think happens in DIPG is through various reasons, and we believe one of those might be ACVR1, which causes the cells to turn it back up and there it's inappropriately turned on. When this happens, it begins dividing and invading in a highly aggressive manner, and it's really a signaling pathway that should have been turned off as soon as the brainstem was developed. Our hope is that this is relevant for the DIPGs even beyond the ACVR1 mutation and that cannabidiol (CBD) or future drugs targeting ID1 can be used to slow that down.”
What does the support of the DIPG Collaborative mean to you and your team?
“Receiving support from the DIPG Collaborative means so much to me and my lab. The funding to pursue this project is critical to making progress, and knowing it was crowd-sourced from a collaboration of family foundations affected by this disease is even more amazing for us. We are looking forward to continuing to build connections and fight this disease with the DIPG Collaborative for many years to come.”